Late Breaking Abstracts

PO0003A / #2365

Topic: AS01 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – NEITHER THROMBOLYSIS NOR THROMBECTOMY

MULTICENTRE RANDOMISED TRIAL OF ACUTE STROKE TREATMENT IN THE AMBULANCE WITH A NITROGLYCERIN PATCH (MR ASAP)

S. Uniken Venema¹, S.A. Van Den Berg², P. Nederkoorn², B. Van Der Worp¹; On behalf of the MR ASAP Investigators

¹University Medical Center Utrecht, Department Of Neurology And Neurosurgery, Brain Center, Utrecht, Netherlands; ²Amsterdam University Medical Centers, University of Amsterdam, Department Of Neurology, Amsterdam, Netherlands

Background and Aims: A pooled analysis of randomised trials has suggested that administration of glyceryl trinitrate (GTN) via a transdermal patch in the first hours after stroke onset increases the chance of a favourable outcome, but this was not confirmed in a subsequent trial. We assessed the effect of transdermal GTN, started within 3 hours of symptom onset in the prehospital setting, on functional outcome at 90 days in patients with presumed acute stroke.

Methods: We performed a phase 3, multicentre, prospective, randomised, open-label, blinded end point (PROBE) trial in the Netherlands. Adults with presumed acute stroke within 3 hours of symptom onset, a face-arm-speech-time score of 2 or 3, and a systolic blood pressure ≥140 mmHg were randomised (1:1) to receive transdermal GTN (5 mg/day for 24 hours) plus standard care or to standard care alone. GTN was started in the prehospital setting and continued in the hospital. The trial used a deferred consent procedure. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days, analysed with ordinal logistic regression. Secondary outcomes included mortality and poor outcome (mRS score 3 to 6) at 90 days. Predefined subgroup analyses included stroke type and treatment with intravenous thrombolysis or endovascular thrombectomy. The target sample was 1400 patients. The trial is registered as ISRCTN99503308.

Results: In June 2021, the trial was terminated because of futility after the inclusion of 326 patients.

Conclusions: Final results will be presented at the Conference.

Trial Registration Number: ISRCTN99503308.

PO0006B / #2103

Topic: AS02 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY

DIRECT MECHANICAL THROMBECTOMY VERSUS BRIDGING THERAPY – CUMULATIVE STUDY-LEVEL META-ANALYSIS OF THE DIRECT-MT, MR CLEAN-NOIV, DEVT, SKIP AND SWIFT-DIRECT RANDOMIZED CONTROLLED TRIALS

U. Fischer¹; on behalf of the Improving Reperfusion strategies in Ischemic Stroke (IRIS) working group investigators (DIRECT MT; MR CLEAN noIV; DEVT; SKIP; SAFE DIRECT; SWIFT DIRECT)

¹University Hospital Bern, Department Of Neurology, Bern, Switzerland

Background and Aims: Whether direct mechanical thrombectomy (MT) in acute ischaemic stroke patients with large vessel occlusion is equally effective as intravenous thrombolysis (IVT) with alteplase followed by MT remains a matter of debate. Primary aim of this study was to test non-inferiority of direct mechanical thrombectomy using summary estimates of study-level aggregate data of all randomized controlled trials evaluating direct MT vs IVT followed by MT. Secondary aims included superiority testing of IVT followed by MT versus direct MT and presentation of relevant secondary outcomes.

Methods: We performed a PROSPERO registered, prespecified, systematic review of electronic databases (Web of Science, PubMed, Embase) and meta-analysis with data presentation adherent to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Random effects models were used to pool the study-level data. The primary outcome used for non-inferiority and superiority testing was good functional outcome at 90 days (mRS ≤ 2). The non-inferiority margin was prespecified. Secondary outcomes included excellent functional outcome (mRS ≤ 1), mortality, symptomatic intracranial haemorrhage, successful reperfusion (TICI ≥ 2b) and procedure-related complications. Five RCTs comprising 2043 patients (xy dMT, yx bridging therapy) were included.

Results: To be determined.

Conclusions: To be determined.

Trial Registration Number: SWIFT DIRECT NCT03192332 MR CLEAN-NO IV ISRCTN80619088 SKIP UMIN000021488 DIRECT-MT NCT03469206 DEVT ChiCTR-IOR-17013568.

PO0014A / #2104

Topic: AS01 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – NEITHER THROMBOLYSIS NOR THROMBECTOMY

CEREBRAL VENOUS SINUS THROMBOSIS FOLLOWING VACCINATION AGAINST COVID-19: A UK MULTICENTRE COHORT STUDY

R. Perry^1,2, A. Tamborska³, B. Singh⁴, B. Craven⁵, R. Marigold⁶, P. Arthur-Farraj⁷, J. Yeo⁸, L. Zhang⁹, G. Hassan-Smith¹⁰, M. Jones¹¹, C. Hutchcroft¹¹, E. Hobson¹², D. Warce^l5, D. White¹⁰, P. Ferdinand¹³, A. Webb¹⁴, T. Solomon⁴, M. Scully⁵, D. Werring², C. Roffe⁶; CVST After Immunisation Against COVID-19 (CAIAC) Collaborators

¹UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Stroke Research Center, Department Of Brain Repair And Rehabilitation, London, United Kingdom; ²National Hospital for Neurology and Neurosurgery, University College London Hospitals, London, United Kingdom; ³University of Liverpool, Institute Of Infection, Liverpool, United Kingdom; ⁴The National Institute for Health Research Health Protection Research Unit for Emerging and Zoonotic Infections, University Of Liverpool, Liverpool, United Kingdom; ⁵University College London Hospitals NHS Foundation Trust, Department Of Haematology, London, United Kingdom; ⁶University Hospital Southampton NHS Foundation Trust, Department Of Stroke Medicine, Southampton, United Kingdom; ⁷University of Cambridge, John Van Geest Centre For Brain Repair, Cambridge, United Kingdom; ⁸Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, United Kingdom; ⁹St George's University Hospitals NHS Foundation Trust, Neurology, London, United Kingdom; ¹⁰University Hospitals Birmingham NHS Foundation Trust, Department Of Neurology, Birmingham, United Kingdom; ¹¹Salford Royal NHS Foundation Trust, Manchester Centre Of Clinical Neurosciences, Manchester, United Kingdom; ¹²Sheffield Teaching Hospitals NHS Foundation Trust, Department Of Neurology, Sheffield, United Kingdom; ¹³University Hospitals of North Midlands NHS Trust, Department Of Stroke Medicine, Stoke-on-Trent, United Kingdom; ¹⁴Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department Of Clinical Neurosciences, University Of Oxford, OXFORD, United Kingdom

Background and Aims: A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous sinus thrombosis (CVST) is its most common manifestation but has not previously been described in detail. Our objectives were to document the features of post-vaccination CVST with and without VITT and to assess whether VITT is associated with a worse outcome.

Methods: We collected clinical characteristics, laboratory results and radiological features on admission of patients with CVST following vaccination against COVID-19. We compared the VITT and non-VITT groups for the proportion of patients who were dead or dependent at the end of admission.

Results: 70 patients with CVST following vaccination against COVID-19 had VITT, and 25 did not. The median age of the VITT group (47 years) was lower than in the non-VITT group (57 years, p = 0.0045). Patients with VITT-associated CVST had more intracranial veins thrombosed (median 3) than non-VITT patients (median 2, p = 0.041) and more frequently had extracranial thrombosis (44%) than non-VITT patients (4%, p = 0.0003). Death or dependency (mRS 3-6) occurred more frequently in VITT-associated CVST (47%) than in non-VITT CVST (13%, p = 0.0020). This adverse outcome was less frequent in VITT patients who received non-heparin anticoagulation (36%) than in those who did not (75%, p = 0.0031) and in those who received intravenous immunoglobulin (40%) than in those who did not (73%, p = 0.022).

Conclusions: CVST is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin may improve outcome of VITT-associated CVST.

Trial Registration Number: Not Applicable (Surveillance Study).

PO0020A / #2133

Topic: AS04 CLINICAL TRIAL RESULTS – REHABILITATION & RECOVERY

NEUROREGENERATION ENHANCED BY TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) IN STROKE (NETS)

C. Gerloff¹, K. Heise², F. Hummel³, R. Schulz¹, S. Wolf¹, A. Zapf¹; The NETS Trial Collaboration Group

¹University Medical Center Hamburg-Eppendorf, Department Of Neurology, Hamburg, Germany; ²KU Leuven, Department Of Movement Sciences - Movement Control And Neural Plasticity Research Group, Leuven, Belgium; ³EPFL, Centre For Neuroprosthetics (cnp) And Brain Mind Institute (bmi), School Of Life Sciences (sv), Geneva, Switzerland

Background and Aims: Neuroregeneration enhanced by transcranial direct current stimulation (tDCS) in stroke (NETS) is an investigator-initiated, interventional, prospective, randomized, double-blind, placebo-controlled trial and tested efficacy and safety of anodal tDCS (1 mA, 20 min) to the primary motor cortex of the lesioned hemisphere in the subacute phase (day 5-45) after cerebral ischemia.

Methods: Stimulation was combined with standardized rehabilitative training and applied in 10 sessions over 2 weeks. After 1:1 randomization of 123 patients (11 centers, 3 European countries, 2009-2019), 119 patients entered the intention-to-treat (ITT) population (mean age ± SD, 66 ± 12; 63% male). Primary outcome was upper-extremity function 1-7 days after the intervention period, measured by the upper-extremity Fugl-Meyer assessment (UEFMA). Secondary endpoints included multiple scores (e.g., ARAT, nine-hole peg test) at multiple time points up to 12 months.

Results: Baseline variables were comparable, mean NIHSS 3.84 ± 1.95 (IQR, 3-5), mean time since stroke 20 ± 12 days (10-28). The intervention was well tolerated. The adjusted mean improvement of UEFMA from baseline was 9.07 in the placebo group and 8.76 with active stimulation (difference -0.31, 95% CI -2.97-2.35; p = 0.820; ITT, ANCOVA). In the per-protocol analysis (94 patients), the respective UEFMA differences were 10.25 for placebo and 10.20 for active stimulation (difference -0.05, 95% CI -3.03-2.93; p = 0.972). There were no relevant differences in secondary endpoints. Both groups showed very good long-term recovery (e.g., UEFMA at 12 months 56.21 ± 9.61 [placebo] and 55.76 ± 13.23 [active stimulation]).

Conclusions: In conclusion, anodal tDCS did not enhance upper extremity recovery in a cohort of mild to moderately affected subacute stroke patients.

Trial Registration Number: NCT00909714.

PO0020B / #2352

Topic: AS01 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – NEITHER THROMBOLYSIS NOR THROMBECTOMY

TIMING OF ORAL ANTICOAGULANT THERAPY IN ACUTE ISCHEMIC STROKE WITH ATRIAL FIBRILLATION: A REGISTRY-BASED RANDOMISED CONTROLLED STUDY

J. Oldgren^1,2, S. Åsberg³, Z. Hijazi^1,2, P. Wester⁴, P. Öhagen¹, B. Norrving⁵; The TIMING Investigators

¹Uppsala University, Uppsala Clinical Research Center, Uppsala, Sweden; ²Uppsala University, Department Of Medical Sciences, Uppsala, Sweden; ³Uppsala University, Department Of Neuroscience, Uppsala, Sweden; ⁴Karolinska Institutet, Department Of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; ⁵Lund University, Department Of Clinical Sciences, Neurology, Lund, Sweden

Background and Aims: Guidelines do not provide evidence-based recommendations on the optimal time-point to start non-vitamin K antagonist oral anticoagulants (NOAC) after acute ischemic stroke in patients with atrial fibrillation (AF). We investigated the efficacy and safety of early vs. delayed initiation of NOAC.

Methods: The TIMING study was a registry-based, randomised, non-inferiority, open-label, blinded endpoint study at 34 out of 72 stroke units in Sweden. The Swedish Stroke Register, with an integrated computerised randomisation module, was used for enrolment and follow-up. Patients were within 72 hours from stroke onset randomised (1:1) to early (≤4 days) or delayed (5-10 days) initiation of NOAC. Primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days. In parallel, a control cohort of patients with acute ischemic stroke and AF receiving early or delayed NOAC within 10 days (without randomisation) was registered.

Results: From April 2017 to December 2020, 888 patients, 78 years (mean), 46% females, were randomized in TIMING, and 9,321 control patients 79 years (mean), 46% females, were registered. Follow-up was at least 90 days for all patients.

Conclusions: This study addresses the important clinical dilemma of NOAC initiation after ischemic stroke in patients with AF. The integration of a randomisation module in the Swedish Stroke Register combines the advantages of a prospective randomised study design with the strengths of a comprehensive clinical register, with the addition of a large control cohort. Study results will be presented at the European Stroke Organisation Conference.

Trial Registration Number: ClinicalTrials.gov Identifier: NCT02961348.

O0113A / #2349

Topic: AS03 CLINICAL TRIAL RESULTS – PREVENTION

ASYMPTOMATIC CAROTID SURGERY TRIAL - 2, AN INTERNATIONAL RANDOMISED TRIAL, COMPARING CAROTID ENDARTERECTOMY WITH CAROTID STENTING FOR LONG-TERM STROKE PREVENTION

L. Bonati¹, R. Bulbulia², H. Pan², R. Peto², A. Halliday³; ACST-2 Collaborators

¹University Hospital Basel and University of Basel, Department Of Neurology And Stroke Center, Basel, Switzerland; ²University of Oxford, Nuffield Department Of Population Health, Oxford, United Kingdom; ³University of Oxford, Nuffield Department Of Surgical Sciences, Oxford, United Kingdom

Background and Aims: In patients with asymptomatic carotid stenosis, carotid endarterectomy (CEA) halves stroke risk over the next 10 years. CEA or carotid stenting (CAS) are now used to treat several hundred thousand patients each year. Whether CEA or CAS is superior in preventing stroke in the long term is unclear. The aim of ACST-2 is to compare (1) peri-procedural risks (myocardial infarction, stroke and death, and (2) stroke in subsequent years, particularly disabling or fatal stroke, between CEA and CAS.

Methods: Between September 2008 and December 2020, from 133 centres in 33 countries, 3638 patients (1084 women, 29.8%) with asymptomatic carotid stenosis were randomly allocated to CEA vs CAS. The median degree of stenosis was 80% (range 60-99%). 1290 (35.5%) patients had coronary artery diasease, 224 (6.1%) had atrial fibrillation, 1088 (29.9%) were diabetic, 234 (6.5%) had a history of remote (>6 months) ipsilateral carotid territory symptoms, and 524 (14.5%) had prior contralateral cerebrovascular symptoms. Medical therapy at randomisation included antiplatelet therapy (3244, 91%), anticoagulation (300, 8.4%), blood pressure lowering (3143, 88.3%) and lipid-lowering therapy (3045, 85.6%).

Results: The results will be presented at ESOC 2021. The number of major events in the periprocedural period and during follow-up (4.85, IQR 2.41-7.76 years) provide good statistical power to detect differences in outcomes, and will provide a reliable assessment of durability to 5 years.

Conclusions: ACST-2 is the largest trial to compare CEA and CAS for stroke prevention in asymptomatic carotid stenosis. Its findings will provide guidance to clinicians worldwide when assessing patients for caroid interventions.

Trial Registration Number: ISRCTN21144362.

O0080A / #2351

Topic: AS01 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – NEITHER THROMBOLYSIS NOR THROMBECTOMY

DAY AND NIGHT IN ACUTE STROKE PREHOSPITAL TRIAGE: A POST-HOC ANALYSIS OF THE RACECAT TRIAL

A. Garcia-Tornel Garcia-Camba¹, D. Matías², M. Rubiera³, M. Olivé-Gadea¹, S. Boned², J. Juega⁴, M. Muchada², J. Pagola¹, M. Requena⁵, C. Piñana⁶, A. Tomasello⁷, D. Rodríguez-Luna¹, N. Rodríguez-Villatoro⁵, C.A. Molina⁸, S. Abilleira⁹, N. Perez De La Ossa¹⁰ and M. Ribo¹

¹Hospital Universitari Vall d'Hebron, Stroke Unit. Department Of Neurology, Barcelona, Spain; ²Vall d'Hebron Hospital, Stroke Unit, Barcelona, Spain; ³Vall d’Hebron University Hospital, Vall D’hebron Institute Of Research (vhir), Barcelona, Spain; ⁴Hospital Universitari de la Vall d'Hebron, Stroke Unit, Neurology, Barcelona, Spain; ⁵Vall d'Hebron University Hospital, Stroke Unit, Barcelona, Spain; ⁶Vall d'Hebron University Hospital, Neurointerventional Radiology, Barcelona, Spain; ⁷Vall d'Hebron University Hospital, Neuroradiology, Barcelona, Spain; ⁸Vall d’Hebron Hospital, The Stroke Unit, Barcelona, Spain; ⁹Institut Catala Salut, Healthcare Management, Barcelona, Spain; ¹⁰Germans Trias Hospital, Badalona, Spain., Neurology, Badalona, Spain

Background and Aims: We aim to assess whether time of day modified the treatment effect of the intervention in the RACECAT trial.

Methods: We performed a secondary analysis of RACECAT to evaluate if direct transfer to a thrombectomy-capable center, as compared to transfer to a local stroke center, influence on functional outcome differed according to treatment allocation time: daytime(8:00AM-8:59PM) and nighttime(9:00PM-7:59AM) in patients with ischemic stroke. Primary outcome was modified Rankin score at 90 days.

Results: Of the 1369 patients in the intention to treat population, 949 patients (67%) had an ischemic stroke (mean age 74 ±13 years; 428 women (45.1%); median RACE score 7 (IQR 6 to 8)); 258 of them (27%) were evaluated during nighttime. The odds of better disability outcomes differed according to time of day, favoring direct transfer to a thrombectomy-capable center during nighttime: adjusted common odds ratio (acOR) during daytime, 0.890 (95% confidence interval (CI) 0.680 to 1.163); acOR during nighttime, 1.620 (95% CI 1.020 to 2.551) (pinteraction = 0.014). Subgroup analysis revealed a significant heterogeneity in the observed interaction across stroke subtypes; influence of nighttime on the intervention effect was only present in patients with large vessel occlusion: acOR during daytime, 0.766 (95% CI 0.548-1.072); acOR during nighttime, 1.785 (95% CI 1.024 to 3.112) (pinteraction = 0.01). Figure 1.

Conclusions: In patients that are evaluated during nighttime for a suspected stroke with high odds of harboring a large vessel occlusion in areas not covered by thrombectomy-capable stroke centers, direct transfer to a thrombectomy-capable center is associated with lower degrees of disability at 3 months.

Trial Registration Number: NCT02795962.

EPP0016A / #2358

Topic: AS03 CLINICAL TRIAL RESULTS – PREVENTION

AUTOMATIC SUPERIOR ARCH VESSELS SEGMENTATION AND STENOSIS RECOGNITION BASED ON ARTIFICIAL INTELLIGENCE THROUGH CT ANGIOGRAPHY IMAGING

P. Fan^1,2, W. Wang², Y. Wang^1,2 and Z. Wu¹

¹Beijing Tiantan Hospital, Capital Medical University, Beijing, National Center For Imaging Research, Beijing, China; ²Capital Medical University, School Of Public Health, Beijing, China

Background and Aims: The intervention of the stenosis of the supraarch vesselses is significant to prevent stroke. While the reconsturction of vessles and the recognition of stenosis need a lot of medical resources and human resources. The study is to realize the automatic extraction of the suprararch blood vessels and the automatic recognition and analysis of the stenosis using the artificial intelligence.

Methods: This system is trained and tested with approximately 800 patients suprararch CTA scans collected from Beijing Tiantan Hospital in China, from June 2018 to October 2019. The patient characteristics and those of the labeled superior arch CTA scans were employed for training, validation, and independent testing. The study includes convolutional neural network based on deep learning-based segmentation approaches which could be accurate vessel segmentation, and centerline tracking, to achieve accurate segmentation extraction of arterial vessel status and recognize the stenosis automatically. We finally establish a high-quality automatic imaging reconstruction system with vessel quality evaluation.Through clinical testing, the system is applied to the clinic to speed up the reading of vascular images and relieve the strain of medical and human resources.

Results: We establish a computer assisted diagnosis tool which could meet the further clinical senator application in multiple condition with the desired level of robustness in the evaluation of the superior arch vascular stenosis.

Conclusions: The automatic post-processing and reading of blood vessel images by artificial intelligence can not only improve the precision and speed of image analysis, but also greatly relieve the pressure of medical and human resources.

Trial Registration Number: Temporary absence.

EPP0020A / #2362

Topic: AS04 CLINICAL TRIAL RESULTS – REHABILITATION & RECOVERY

OPTIMIZED TREATMENT SCHEDULE OF MANNITOL FOR SEVERE ISCHEMIC STROKE OR MASSIVE CEREBRAL INFARCTION: A PROPENSITY SCORE-MATCHED, PROSPECTIVE MULTI-CENTER COHORT STUDY

K. Ye and M. Liu¹

¹四川大学华西医院, 神经学, 四川省成都市, China

Background and Aims: Patients with severe/massive ischemic stroke (SMIS) are prone to brain edema, even malignant brain edema, which is a major cause for disability and mortality. Mannitol is widely used to treat brain edema in clinical practice, but its evidence is limited. Furthermore, the optimal timing, dosage, and duration of mannitol is unknown.

Methods: We performed a multi-center, prospective cohort study from July 2017 to September 2019. Patients (age > = 18 years) with SMIS who had used mannitol were eligible for inclusion. Patients with pre-morbid MRS>2 were excluded. Patients were stratified on the basis of the treatment schedule of mannitol they had received. Patients were matched on the basis of demographics, past medical history, etc. using PSM. The endpoints were 3-month outcomes and complications. Univariate analysis was performed to compare outcomes.

Results: 401 patients were included (age: 70.9 ± 13.5 and 53.1% male). The median duration was 8 days [(IQR): 4-14 days]. The median daily average dose was 75g/day (IQR: 50-95g/day). Patients with early action use of mannitol were not associated with 3-month mRS 3-6 (OR = 1.084, P = 0.858), increased risk of acute kidney injury (OR = 1.909, P = 0.063), small-dose group associated with reduced risk of 3-month mRS 3-6 (OR = 0.423, P = 0.085) and reduced risk of acute kidney injury (OR = 0.408, P = 0.017). Short-term use of mannitol was not associated with 3-month mRS 3-6 and complications.

Conclusions: This study indicated that within 6-hours, low dose and 1-week course may be a better strategy to improve the 3-month outcomes and reduce the complications of mannitol for patients with severe /massive ischemic stroke.

Trial Registration Number: Not Applicable.

EPV0113A / #2310

Topic: AS04 CLINICAL TRIAL RESULTS – REHABILITATION & RECOVERY

INTER-METHOD RELIABILITY OF THE MODIFIED RANKIN SCALE IN PATIENTS AFTER SUBARACHNOID HEMORRHAGE

E. Nobels¹, E. Postma², I. Abma³, J. Van Dijk⁴, R. Haeren⁵, I. De Ridder⁶, W. Moojen⁷, H. Den Hertog⁸, D. Nanda⁹, A. Potgieser⁴, W. Verhagen¹⁰, P.J. Van Der Wees¹¹, R. Bartels¹, D. Verbaan¹² and H. Boogaarts¹³

¹Radboud university medical center, Neurosurgery, Nijmegen, Netherlands; ²Amsterdam UMC, Neurosurgery, Amsterdam, Netherlands; ³Radboud university medical center, Iq Healthcare, Nijmegen, Netherlands; ⁴University medical center Groningen, Neurosurgery, Groningen, Netherlands; ⁵MUMC+, Neurosurgery, Maastricht, Netherlands; ⁶Maastricht University Medical Center+, Neurology, Maastricht, Netherlands; ⁷Haaglanden Medical Center, Neurosurgery, Den Haag, Netherlands; ⁸Isala Hospital, Neurology, Zwolle, Netherlands; ⁹Isala hospital, Neurosurgery, Zwolle, Netherlands; ¹⁰Canisius Wilhelmina Hospital, Neurology, Nijmegen, Netherlands; ¹¹Radboud University Medical Center, Radboud Institute For Health Sciences, Iq Healthcare, Nijmegen, Netherlands; ¹²Amsterdam University Medical Centers, Neurosurgery, Amsterdam, Netherlands; ¹³Radboud University Medical Center, Neurosurgery, Nijmegen, Netherlands

Background and Aims: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients after an aneurysmal subarachnoid hemorrhage. The assessment method of the mRS is often not clearly described in trials, while the method might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS.

Methods: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥18 years with an aneurysmal subarachnoid hemorrhage were randomized either to a structured interview or self-assessment of the mRS. In total, 150 patients were included and seen by a physician who determined an mRS score, followed by either the structured interview or self-assessment. Inter-method reliability was measured using the quadratic weighted kappa score and percentage of agreement.

Results: The quadratic weighted kappa was 0.60 between the assessment of the physician and a structured interview and 0.57 between assessment of the physician and self-assessment. Percentage agreement was respectively 50.8% and 21.4%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician.

Conclusions: The mRS scores obtained with different assessment methods differ significantly, with higher (i.e. worse) scores obtained from self-assessment and structured interviews. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials.

Trial Registration Number: URL: www.trialregister.nl; Unique identifier: NL7859.

EPV0542A / #2372

Topic: AS01 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – NEITHER THROMBOLYSIS NOR THROMBECTOMY

LARGE SCALE, CT EVALUATION CAN IMPROVE ACCESS TO IMAGING STUDIES WITHIN MULTI-CENTER STROKE TRIALS

B. Jankowitz¹

¹Penn medicince, Neurosurgery, Philadelphia, United States of America

Background and Aims: Introduction: Artificial intelligence (AI) can automate the detection and triage of Intracerebral Hemorrhage (ICH). Early Minimally invasive Removal of IntraCerebral Hemorrhage (ENRICH) is a RCT evaluating the efficacy of minimally invasive surgery for ICH. AI ENRICH is a prospective trial operating within and in parallel to the ENRICH trial that utilizes an AI application, Viz RECRUIT ICH Volume, to identify and segment ICH to quickly identify potentially eligible subjects.

Methods: Non-contrast CT scans performed at 4 participating US hospitals were evaluated specifically for a parenchymal hemorrhage by Viz RECRUIT ICH Volume. Participating health care professionals downloaded a phone application that allowed users to be notified for any hemorrhage ≥ 5 mL. Time metrics included the onset of CT scan, phone alert, and user recognition of that alert.

Results: Over a combined period of 524 days 42,962 CT scans were evaluated by the Viz ICH VOLUME application. Of these, 1433 CT scans were determined to contain an ICH yielding a total of 266 patients that met ENRICH criteria for trial inclusion (30-80 mL). For scans viewed in less than 120 minutes - the median time from CT scan to cell phone notification was 2.65 minutes. The median time from cell phone notification to the user viewing the CT scan was 3.3 minutes.

Conclusions: Viz ICH VOLUME can screen large numbers of CT scans and send alerts within minutes to medical professionals searching for clinical trial candidates in time-sensitive environments. Studies relying on radiographic selection criteria may benefit from automated screening.

Trial Registration Number: 21249944999949.

EPV0551A / #2132

Topic: AS04 CLINICAL TRIAL RESULTS – REHABILITATION & RECOVERY

RISK FACTORS FOR FRACTURES IN WOMEN WITH ISCHEMIC STROKE: 10-YEAR PROSPECTIVE FOLLOW-UP

V. Shishkova¹, O. Kosmatova², I. Skripnikova¹, O. Drapkina¹; Prevention medicine

¹National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Health of Russia, Preventive Medicine, Moscow, Russian Federation; ²National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Health of Russia, Prevention Osteoporosis, Moscow, Russian Federation

Background and Aims: To study the link between various risk factors and an occurrence of osteoporotic fractures (OPF) in women who have had a first ischemic stroke (IS).

Methods: The study included 170 women 45 to 80 years of age who have had the first IS and received neurorehabilitation treatment for post-stroke disorders in 2011. For all women, the ten-year absolute risk of major OPF and hip fractures (HF) was retrospectively analyzed using the FRAX algorithm, excluding the data on bone mineral density. In 2021, a telephone survey was conducted to register the fractures that occurred over the past period of time. The SPSS Version 20 was used for statistical analysis of the results.

Results: During the 10 year, OPF and HF occurred in 34 (20%) women (fractures of fingers, toes, and skull bones were excluded). The absolute risk of in women with a low-traumatic fracture was higher than in patients without it (p < 0.001). Correlation analysis demonstrated the association between the occurrence of low-traumatic fractures in patients who had the first IS and the following parameters: age (r = 0.277; p < 0.001), weight (r = −0.368; p < 0.001), body mass index (r = −0.378; p < 0.001), total cholesterol concentration (r = 0.189; p = 0.014), type 2 diabetes mellitus (φ = 0.225; p = 0.003), HF in parents (φ = 0.375; p < 0.001).

Figure 2.

Conclusions: The study demonstrate the presence of an association between the occurrence of low-traumatic fractures in with women prior IS and traditional risk factors included in the FRAX algorithm, as well as new like with type 2 diabetes mellitus.

Trial Registration Number: Local number (in Russia) 132021.

EPV0552A / #2317

Topic: AS03 CLINICAL TRIAL RESULTS – PREVENTION

A STUDY OF ETIOLOGICAL FACTORS OF ISCHAEMIC STROKE IN PATIENTS OF THE AGE GROUP 18 TO 45 YEARS

S. Garg¹, P. Renjen² and D. Chaudhari³

¹Indraprastha Apollo Hospital, Internal Medicine, New Delhi, India; ²Indraprastha Apollo Hospital, Neurology, New Delhi, India; ³Indraprastha Apollo Hospital New Delhi, Neurosciences, New Delhi, India

Background and Aims: While evaluating stroke in young, uncommon aetiologies like arterial dissection, connective tissue disorders and prothrombotic states need to be considered. Tubercular meningitis and bacterial meningitis remain an important cause in developing countries. Modifiable risk factors like hypertension, smoking and drug abuse are prevalent making primary prevention of stroke all the more important here. Aim–To study the etiological factors of ischaemic stroke in patients of the age group 18 to 45 years.

Methods: Prospective observational Single center study in Indraprastha Apollo Hospital, New Delhi from September 2018 to December 2019. Taking 80% power, 5% significance level with 0.15 precision, calculated sample size was 39. Patients in age group 18 to 45 years with acute ischaemic stroke were evaluated using a pre designed semi-structural proforma.

Results: 50 patients were included. Alcohol (36%) and smoking (30%) followed by hypertension (22%) were important risk factors. Significant proportion had prothrombotic state. Fig. 1 shows distribution of patients according to hypercoagulable state. Large-artery atherosclerosis was most common subtype followed by stroke of other determined etiology. Association of hypertension with ischaemic stroke subtypes was statistically significant (p = 0.01). Hypertension was the major risk factor in small vessel disease (n = 60; 92.3%) and undetermined etiology (n = 13; 56.5%) with p = 0.023 and p < 0.001, respectively.

Figure 3.

Conclusions: Hypertension has significant association with more than one stroke subtype in young. Strict control of hypertension with antihypertensive therapy and lifestyle changes is needed. Since there is increasing prevalence of smoking in young, early implementation of awareness programmes aimed at young school going population is desirable.

Trial Registration Number: ESR/5/Inst/DL/2013/RR-16.

EPV0559A / #2369

Topic: AS02 CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY

STENTING IN INTERNAL CAROTID ARTERY DISSECTION – A SINGLE CENTER COHORT ANALYSIS

C. Brunner¹, W. Struhal¹ and C. Nasel²

¹University Clinic Tulln, Karl Landsteiner University of Health, Neurology, Tulln, Austria; ²University Clinic Tulln, Karl Landsteiner University of Health, Radiology, Tulln, Austria

Background and Aims: Carotid artery dissection is the leading cause of ischemic stroke in the young population. Pathophysiological it results from intimal tearing and blood flow into the false lumen, causing vessel narrowing, aneurysm formation or both. The goal of treatment is to prevent (recurrent) strokes, to avoid complications and should be individualized.

Methods: 15 patients with spontaneous extradural ICA dissection and acute ischemic stroke were included in our analysis. 8 patients treated with emergent stenting, 7 patients with medical therapy. Following parameters were compared amongst the two groups: age, sex, comorbidities, location of dissection, clinical presentation at onset, at discharge, after 3 and 6 months, recanalization rate, procedural complications, medical therapy, mortality.

Results: In the stenting group 75% were presented with ICA occlusion, 25% >50% ICA stenosis. In the medical group 57% had an occlusion at stroke onset and 43% >50% ICA stenosis. The stenting group was clinical more severely affected with mean NIHSS 10 ± 6 versus 3 ± 6 at stroke onset, whereas after 3 months in each group a good clinical outcome was reached (mRS 1 ± 1), mean NIHSS 3 ± 3 versus 2 ± 4. Complete recanalization rate was 88% (stent) versus 57% (medical) after 6 months. Acute phase complications with new ischemic lesions on brain imaging was seen in 38% versus 29%. Symptomatic intracranial hemorrhage occurred in 12% versus 14%.

Conclusions: Stenting in ICA dissection should be considered as a feasible rescue treatment in selected cases of recurrent cerebral ischemic events, progressive/fluctuating neurological symptoms or severely affected patients despite optimal medical treatment.

Trial Registration Number: not available.

EPV0559B / #2129

Topic: AS04 CLINICAL TRIAL RESULTS – REHABILITATION & RECOVERY

ENHANCING THE QUALITY OF LIFE AND COMMUNICATION ABILITIES FOR PEOPLE WITH ANOMIC APHASIA BY USING TALKING MATS IN SPEECH AND LANGUAGE THERAPY

V. Eden¹, E. Pampoulou¹, M. Kambanaros¹; Cyprus University of Technology7Department of Rehabilitation Sciences

¹Cyprus University of Technology, Rehabilitation Sciences, Limassol, Cyprus

Background and Aims: Talking Mats (TM) is a communication method that belongs to the field of Augmentative and Alternative Communication. TM can support people with complex communication needs, such as individuals with anomic aphasia. Extensive research on TM has focused primarily on its use as a communication tool (Murphy, Cameron & Boa, 2013). This study explores, for the first time, the effects of using TM in a speech and language intervention as a treatment method for enhancing communication abilities and the Quality of Life for a person with anomic aphasia.

Methods: Single case study with a multiple baseline design. The participant was a 35-year old female with mild, anomic aphasia, six years post onset. At baseline, the Western Aphasia Battery and the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39) were administered to the participant. This was followed by 10 consecutive days of intervention with TM focusing on word retrieval and discourse production.

Results: Outcomes and Results: Word fluency improved by 25.58% from baseline, whilst the mean of the psychosocial score on the SAQOL-39 decreased by 9.86% from baseline levels, revealing the lockdown conditions during the global Covid-19 pandemic.

Conclusions: The TM framework might not only serve as a communication tool, but also as a treatment method for training vocabulary recall and discourse for people with anomic aphasia.

Trial Registration Number: EEBK 2017 37.

EPV0543A / #1590

Topic: AS03 CLINICAL TRIAL RESULTS – PREVENTION

A STUDY OF ASSOCIATION BETWEEN MEAN PLATELET VOLUME AND SEVERITY OF ACUTE ISCHAEMIC STROKE ASSESSED BY MODIFIED RANKIN SCALE

D. Chaudhari¹, C. Gupta¹, P. Renjen¹ and S. Garg²

¹Indraprastha Apollo Hospital New Delhi, Neurosciences, New Delhi, India; ²Indraprastha Apollo Hospital, Internal Medicine, New Delhi, India

Background and Aims: Increased platelet size has been described in patients with vascular risk factors. Large platelets are metabolically more reactive, produce more prothrombotic factors and aggregate more easily. Aims- (1). To determine the mean platelet volume in patients of acute ischaemic stroke. (2). To compare the mean platelet volume between cases and controls. (3). To study the association between Mean Platelet Volume (MPV) and the severity of acute ischaemic stroke assessed by Modified Rankin Scale.

Methods: The study was a case control study which was conducted at Indraprastha Apollo Hospitals Delhi. The study was carried in 100 patients diagnosed with an acute ischaemic stroke within 48 hours of onset of symptoms presenting to the hospital emergency, ICU or wards 100 age and sex matched controls were also recruited. A blood sample was collected from the antecubital vein using a 5 ml Syringe and transferred to an EDTA vacutainers.

Results: MPV was found to be higher in patients of acute ischaemic stroke as compared to controls. This finding is similar to study of Durdu Tamer et al. who found MPV higher in patients of ischaemic stroke as compared to controls. There was a positive correlation between Age (Years) and MPV (fl), and this correlation was statistically significant (p = 0.008).

Figure 4. Figure 5.

Conclusions: Our study showed that MPV is higher in patients of acute ischaemic stroke as compared to controls. Hence, MPV can be regarded as an independent risk factor for ischaemic stroke. Elevated MPV is associated with more severe morbidity ie. Higher MRS.

Trial Registration Number: 323-20120-181-217185.

EPP0073 / #1513

Topic: AS08 REHABILITATION – EXCLUDING CLINICAL TRIAL RESULTS

THE IMPACT OF BASELINE SEVERITY AND DOSE ON THE TRAJECTORY OF TREATMENT-FACILITATED SOMATOSENSORY RECOVERY AFTER STROKE: A META-ANALYSIS OF 29 SINGLE-CASE INTERRUPTED TIME-SERIES

L. Carey¹ and T. Matyas¹

¹La Trobe University, Occupational Therapy, Social Work And Social Policy, Melbourne, Australia

Background and Aims: Treatment-facilitated recovery occurs after stroke. However, recovery is often variable and quantifying the trajectory is challenging. We sought to quantify treatment-facilitated recovery associated with delivery of a neuroscience-based therapy known as SENSe. Specifically, we aimed to quantify the magnitude and trajectory of change in somatosensory function associated with somatosensory discrimination training.

Methods: Data from 29 single-case interrupted time-series was analysed. Training effects were measured across texture (n = 20) and proprioceptive (n = 9) discrimination domains. Individual time-series data was modelled across baseline and intervention phases. Effect-sizes and meta-analyses were computed. Magnitude and rate of improvement were investigated relative to the severity of baseline impairment and treatment dose.

Results: Overall large improvements in both modalities were evident, with the vast majority achieving sufficient improvement to end in the unimpaired range. The overall pooled effect-size was 96.6 standardized units (95%CI: 72.7 to 120.6), with the sample showing very large heterogeneity (I2 = 96%, Q = 732.9, p < 0.001). More severe impairments were accompanied by larger magnitude recoveries. The treatment dose required to achieve unimpaired performance varied substantially and did not clearly relate to either baseline severity, nor size of the overall gain during the intervention phase.

Conclusions: The pooled effect-size analysis indicates a very large intervention effect overall, sufficient for most participants to move into the healthy performance range, or a little below. Treatment dose to achieve performance within the unimpaired range was variable. Substantial variation in intervention effect sizes remains to be explained by factors other than initial impairment and somatosensory domain.

Trial Registration Number: Not applicable.

EPP0140 / #880

Topic: AS14 CLINICAL PRACTICE, MANAGEMENT AND CARE

QASC IN ITALY: IMPLEMENTATION OF EVIDENCE-BASED STROKE CARE PROGRAM TO MANAGE FEVER, HYPERGLYCAEMIA (SUGAR) AND SWALLOWING (FESS) IN STROKE PATIENTS – A.O.U. SENESE EXPERIENCE

P. Piscitelli¹, M. Colaiacovo¹, V. Mechini¹, S. Santucci¹, A. Urso², G. Alicastro³, R. Tassi¹ and G. Martini¹

¹University Hospital of Siena, Neurology/stroke Unit Area, Siena, Italy; ²Hospital Network Area-Regional Health Department, Regione Lazio, Health Department, Lazio, Italy; ³university hospital umberto I, Neurology, roma, Italy

Background and Aims: The Quality in Acute Stroke Care (QASC) Trial demonstrated that multidisciplinary, nurse-led interventions to manage fever, hyperglycaemia and swallow difficulties following acute stroke significantly improved health outcomes. Results showed that supported implementation of the Fever, Sugar, Swallow (FeSS) clinical protocols resulted in 16% decreased death and dependency at 90-days.

Methods: According to the international QASC protocol, the first phase of the study was observational. The observation phase included the audit of 45 consecutive medical records of hospitalized stroke patients in 2019. Afterwards, throughout 2020, the FeSS protocols have been implemented as assisted practice.

Results: The data analysis has showed how the nursing approach in adopting these three parameters have significantly improved after the implementation of the FeSS protocols. From pre to post implementation there was an increase in the proportion of patients who: were monitored four times a day for fever on Day 1 (58% vs 96% respectively), Day 2 (73% vs 96%) and Day 3 (71% vs 96%). There was an increase in the proportion of patients observed four times daily for hyperglycaemia on day 1 (60% vs 91% respectively) and day 2 (73% vs 91%). Finally, an increase in the proportion of patients who received a formal swallow screen (49% vs 80%).

Conclusions: This result has clearly demonstrated how the use of standardized protocols have improved the cure and treatments of stroke patients. Finally, this approach contributed to a better quality of life in the post-acute phase of stroke.

Trial Registration Number: Not applicable.

EPP0192 / #712

Topic: AS16 PROGNOSIS AND OUTCOME AFTER STROKE

ASSOCIATION OF HYPOTENSION DURING THROMBECTOMY AND OUTCOMES DIFFERS WITH THE POSTERIOR COMMUNICATING ARTERY PATENCY

E. Robichon¹, B. Maier¹, R. Bourcier¹, C. Dargazanli², J. Labreuche³, L.-A. Thion¹, M. Leguen⁴, R. Riem⁵, J.-P. Desilles¹, G. Boulouis⁶, F. Delvoye¹, S. Hebert¹, H. Redjem¹, S. Smajda¹, S. Escalard¹, R. Blanc¹, M. Piotin¹, B. Lapergue⁷ and M. Mazighi¹

¹Fondation Ophtalmologique A. de Rothschild, Interventional Neuroradiology Department, Paris, France; ²Guy de Chauliac Hospital, Diagnostic And Interventional Neuroradiology, Montpellier, France; ³Univ. Lille, Metrics : Évaluation Des Technologies De Santé Et Des Pratiques Médicales, Lille, France; ⁴Foch Hospital, Anesthesiology, Suresnes, France; ⁵Nantes Hospital, Anesthesiology, Nantes, France; ⁶Tours University Hospital, Neuroradiology, Tours, France; ⁷Foch Hospital, Stroke Center, Suresnes, France

Background and Aims: Hypotension during endovascular therapy (EVT) for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during EVT had the same effect on FO according to the posterior communicating artery (PComA) patency.

Methods: We performed a post-hoc analysis of the Contact Aspiration vs Stent Retriever for Successful Revascularization trial. Patients were included if they had middle cerebral artery (MCA) occlusions. Primary outcome was favorable FO, defined by a modified Rankin scale between 0-2 at 3 months.

Results: 148 patients with MCA occlusion were included. In patients with no PComA, an increase in minimum MAP was positively associated with favorable FO (OR per 10 mmHg increase, 1.59; 95%CI, 1.11-2.25; p = 0.010), whereas no association was found in patients with a PComA (OR = 0.77; 95%CI, 0.54-1.08; p = 0.12). Patients with no PComA and longer cumulative time with MAP<90 mmHg or SBP<140 mmHg had significantly lower rates of favorable FO, with an OR per 10 min increase of 0.75 (95% CI, 0.59-0.94; p = 0.010 and 0.74; 95%CI, 0.60-0.91; p = 0.003, respectively), but not in patients with a PComA.

Conclusions: Hypotension during EVT for MCA occlusion is consistently associated with worse FO in patients with no PComA but not in those with a PComA.

EPP0294 / #1289

Topic: AS30 EXPERIMENTAL/TRANSLATIONAL MEDICINE

NADPH OXIDASE IS ESSENTIAL FOR ENDOTHELIAL PROGENITOR CELL MIGRATION, PROLIFERATION AND VASCULAR REPAIR

M. Alwjwaj¹, R. Kadir¹ and U. Bayraktutan¹

¹University of Nottingham, Division Of Stroke Medicine, Nottingham, United Kingdom

Background and Aims: Endothelial progenitor cells (EPCs) contribute to repair of endothelial layer of the blood-brain barrier following an ischaemic insult. This study has assessed the specific contribution of NADPH oxidase, an important source of vascular oxidative stress, to migration, proliferation and endothelium-reparative capacity of EPCs.

Methods: An in vitro model of human blood-brain barrier (BBB) was constructed by co-culture of a functional subtype of EPCs called outgrowth endothelial cells (OECs) or human brain microvascular endothelial cells (HBMECs) with astrocytes and pericytes. The ability of EPCs to form tight junctions was assessed by cellular staining of zonula occludens-1 (ZO-1). OECs were exposed to a superoxide generator (pyrogallol, 100 µM) in the absence or presence of gp91ds-tat (50µM), an NADPH oxidase inhibitor prior to assessment of cellular proliferation rate (wound scratch assay), cytoskeletal organisation (actin filament staining), migration rate and tubulogenesis.

Results: Both HBMECs and OECs formed equally effective tight junctions and BBB. While exposure to pyrogallol slightly increased both cellular proliferation and stress fibre formation in OECs, treatment with gp91ds-tat delayed their proliferation rates, migratory capacity and tubulogenic function, a marker of angiogenesis in vivo.

Conclusions: Regulation of oxidative stress through specific targeting of NADPH oxidase needs close attention while OECs are being used vasculoreparative therapeutics.

Trial Registration Number: Not applicable.

EPP0327 / #724

Topic: AS35 TECHNOLOGY INNOVATIONS: ROBOTS, VIRTUAL REALITY, ARTIFICIAL INTELLIGENCE AND MORE

ELECTRICAL IMPEDANCE SPECTROSCOPY CAN BE USED TO DIFFERENTIATE CLOT ANALOGS OF DIFFERENT COMPOSITION

P. Messina¹, C. Garcia^2,3, J. Rambeau¹, J. Darcourt^2,4, F. Bozsak¹, B. Payrastre^2,3, C. Cognard^2,4; on behalf of Sensome Collaborators: Ronan Balland, Abdul Barakat, Bruno Carreel, Myline Cottance, Elena Gusarova, Julie Lafaurie, Gor Lebedev

¹Sensome, Sensome, Massy, France; ²INSERM, Umr 1048, Toulouse, France; ³Toulouse University Hospital, Hematology Laboratory, Toulouse, France; ⁴Toulouse University Hospital, Interventional Neuroradiology, Toulouse, France

Background and Aims: Despite the uncontested efficacy of endovascular thrombectomy (EVT) to treat large vessel occlusion acute ischemic stroke (AIS), recent data suggests that fibrin/platelet-rich thrombi are more resistant to EVT and present worse revascularization outcomes compared to red-blood-cell-rich (RBC-rich) thrombi, which are associated with a reduced number of recanalization maneuvers and better clinical outcomes. As an alternative to the limited capabilities of pre-stroke imaging, we investigated the capacity of electrical impedance spectroscopy (EIS) to determine thrombus composition.

Methods: Using a custom sensor, we acquired a database of electrical impedance spectra of 109 ex-vivo generated swine blood thrombus analogs of variable composition placed in a blood flow loop. Thrombi were categorized as “white” without any RBC, “mix” containing some RBC and “red” containing mainly RBC. This swine thrombus database was used to train a machine-learning model predicting the category of a thrombus.

Results: The global accuracy of the model is 86% ([80%, 90%] = 95% confidence interval) with high sensitivity and specificity for each category. The confusion matrix (Figure 1) reveals that most errors occur in between predicting white and mix categories since mixed thrombi can have a low percentage of RBC. Differentiating any thrombus from flowing blood can be achieved with a high sensitivity of 95% [90%, 98%]. Applied to a database of ex-vivo generated human blood thrombus analogs the global accuracy of the model is 79% [71%, 86%].

Figure 6.

Conclusions: These results demonstrate that EIS can be used to determine AIS thrombus composition, and that swine and human thrombus analogs largely share electrical features.

Trial Registration Number: Not applicable.

EPV0030 / #1698

Topic: AS05 THROMBOLYSIS – EXCLUDING CLINICAL TRIAL RESULTS

CLOT STRUCTURE AFFECTS THROMBOLYTIC SUSCEPTIBILITY TO ALTEPLASE IN VITRO

S. Thalerová^1,2,3, M. Pešková^2,3, J. Víteček^2,4, K. Marečková^5,6, A. Gillavry Danylevska^5,6, L. Kubala^2,4, A. Hampl^5,6 and R. Mikulik¹

¹International Clinical Research Center, St. Anne’s University Hospital Brno, Neurology Department, Brno, Czech Republic; ²Institute of Biophysics of the Czech Academy of Sciences, Department Of Biophysics Of Immune System, Brno, Czech Republic; ³Faculty of Science, Masaryk University, Department Of Biochemistry, Brno, Czech Republic; ⁴International Clinical Research Center, St. Anne’s University Hospital Brno, Center Of Biomolecular And Cell Engineering, Brno, Czech Republic; ⁵Faculty of Medicine, Masaryk University, Department Of Histology And Embryology, Brno, Czech Republic; ⁶International Clinical Research Center, St. Anne’s University Hospital Brno, Department Of Cell And Tissue Regeneration, Brno, Czech Republic

Background and Aims: Clot architecture is associated with susceptibility to thrombolysis, but the features behind increased thrombolytic resistance are not completely understood. The aim of the study was to investigate the effect of clot composition and structure on alteplase induced thrombolysis in vitro.

Methods: Six different types of in vitro clots prepared from human blood or its components were used. Clots were treated with alteplase (1.3 mg/L) in in vitro static model, followed by histological analysis (hematoxylin-eosin, Mallory-azan and von Willebrand factor stain). Thrombolysis rate was primarily measured by clot weight loss; histological sections of clots were evaluated microscopically with subsequent image analysis.

Results: Alteplase-induced clot weight loss was as follows (95% confidence interval): erythrocytes dominant 6.7-31.9%; fibrin dominant 18.6-29.8%; plasma 0.9-6.3%; semi-synthetic (erythrocytes 4.2*109/mL) 26.5-30.7%; semi-synthetic (erythrocytes 2.5*109/mL) 20.1-24.9% and semi-synthetic (erythrocytes 8.3*108/mL) 25.3-35.9%. Image analysis showed that after alteplase-induced thrombolysis, erythrocyte dominant clots had loss in erythrocytes content and fibrin dominant clots in fibrin and leukocytes. There was a minor change in plasma clots structure. Semi-synthetic clots (erythrocytes 4.2*109/mL) showed minor loss of erythrocytes, semi-synthetic clots (8.3*108/mL) loss in fibrin and leukocytes, whereas semi-synthetic clots (erythrocytes 2.5*109/mL) lost leukocytes predominantly. The highest vWF content was detected in plasma clots.

Conclusions: Densely packed plasma clots and semi-synthetic clots (erythrocytes 2.5*109/mL) showed the highest resistance to thrombolysis. The highest content of vWF in plasma clots may mediate resistance to thrombolysis.

EPV0043 / #1070

Topic: AS06 HYPERACUTE MANAGEMENT – EXCLUDING CLINICAL TRIAL RESULTS

ENDOVASCULAR MANAGEMENT OF ACUTE ISCHEMIC STROKE DUE TO TANDEM OCCLUSIONS: REAL-WORLD INSIGHTS FROM THE BUENOS AIRES REGISTRY OF TANDEM OCCLUSIONS

J.J. Cirio¹, C. Ciardi², I. Lylyk³, E. Scrivano², J. Lundquist², C. Bleise², N. Perez² and P. Lylyk²

¹Clinica La Sagrada Familia-ENERI, Stroke Units, CAPITAL FEDERAL, Argentina; ²Instituo Medico ENERI-Clinica La Sagrada Familia, Stroke Units, CAPITAL FEDERAL, Argentina; ³Insituto Medico ENERI-Clinica La Sagrada Familia, Neurointerventional Surgery, Bs As, Argentina

Background and Aims: Tandem occlusions (TO) represent a major challenge for endovascular treatment. Several pathophysiological considerations must be pondered to choose the best endovascular strategy. This study aims to describe our experience in the endovascular treatment of acute ischemic stroke (AIS) due to TO of the anterior territory and report our results according to the interventional approach:proximal-first versus distal-first.

Methods: Patients with AIS were identified retrospectively from our database in a comprehensive stroke center between January 2015 and October 2019 due to TO. Baseline characteristics, procedural data, and treatment times were reviewed. Endpoints include good recanalization of both distal and proximal occlusions, symptomatic intracranial hemorrhage (sICH), and functional outcome at 90 days (mRS).

Results: There were 268 patients undergoing EVT for AIS with LVO from the anterior territory. Of these, 40 (14.9%) strokes were associated with TO and met the inclusion criteria. The cause of cervical lesions was atheromatous disease in 85%. Distal approach was used in 22 patients (55%) of the cases. No significant differences were identified regarding the therapeutic strategy used. Functional independence at 90 days (mRS ≤ 2) was achieved in 50% and successful reperfusion (mTICI 2b/3) was obtained in 33 patients (82.5%). Non-differences were identified in patients who received fibrinolytic therapy regarding sICH, clinical independence and reperfusion. Mortality rate at 90 days was 12.5%. Emergent cervical carotid artery stenting was performed in 97.5% of patients.

Conclusions: Our study indicates that the treatment of AIS related to TO using both endovascular strategies, distal-first versus proximal-first, with emergent carotid artery stenting is safe and feasible.

EPV0090 / #495

Topic: AS07 NEUROINTERVENTION – EXCLUDING CLINICAL TRIAL RESULTS

SEVERE HYPOPERFUSION AS AN IMAGING BIOMARKER MAY PREDICT UNFAVORABLE EFFECTIVENESS OF THROMBECTOMY IN ACUTE ISCHEMIC STROKE

M. Fu¹, X. Dong², Z. Yuan¹, Y. Lan³, L. Jiang¹, R. Meng¹, J. Yang⁴ and J. Li¹

¹Affiliated Hospital of Southwest Medical University, Department Of Neurology, Luzhou City, Sichuan Province, China; ²Neusoft Medical Systems Co., Ltd., Artificial Intelligence And Clinical Innovation Institute, Beijing, China; ³Affiliated Hospital of Southwest Medical University, Department Of Radiology, Luzhou City, Sichuan Province, China; ⁴Neusoft Research of Intelligent Healthcare Technology, Co. Ltd., Shengyang, Artificial Intelligence And Clinical Innovation Research, Shenyang, China

Background and Aims: Although the instant recanalization rate of thrombectomy is high, about 40% of treated ischemic stroke patients still cannot benefit from it. In this clinical investigation, we aimed to reveal the predictive association of severe hypoperfusion within those treated but not benefitted patients.

Methods: The consecutive data between September 2018 and October 2020 of the stroke patients who underwent acute thrombectomy within 24hrs were retrospectively analyzed. All volumetric measurements of delayed perfusion time and infarct (Tmax>12 s, 10 s, 8 s, 6 s; rCBF<30%; hypoperfusion intensity ratio, HIR) were done by automated postprocessing suite on CT perfusion. The data were compared and analyzed between two groups: mRS ≤ 2 (favorable outcome) and mRS>2 (unfavorable outcome) at 90 days. Mann-Whitney test and multivariate regression were used for the analyses.

Results: Ninety-nine patients were included (36 for mRS ≤ 2; 63 for mRS >2). A significantly higher baseline NIHSS was seen in the group with unfavorable outcome (11 (6-17) vs 9 (2.25-15.75), P = 0.007). A larger volume of severe hypoperfused lesion (Tmax>12 s, 25.12(10.51-36.41) mL vs 4.32(2.43-20.9) mL, P = 0.006; Tmax>10 s, 45(28.96-67.29) mL vs 12.71(6.32-40.49) mL, P = 0.016) and moderately hypoperfused lesion (Tmax>8 s,69.2(49.12-92.98) mL vs 27.92(15.35-72.71) mL, P = 0.04), and higher HIR (0.38(0.3-0.45) vs 0.23(0.17-0.38), P = 0.002) were observed in the unfavorable outcome group. Moreover, Tmax>10s (OR 1.055, P = 0.023) and 8 s (OR 0.949, P = 0.018) were independent predictors of clinical outcome.

Figure 7.

Conclusions: In our cohort study, the preliminary results showed severe and moderate hypoperfusion with a higher HIR value may predict unfavorable outcomes for patients not benefitted from thrombectomy.

EPV0177 / #1950

Topic: AS12 IMAGING – NON ACUTE INCLUDING NEUROSONOLOGY

CEREBRAL HEMODYNAMICS IN MIGRAINE PATIENTS TREATED WITH ANTI-CGRP RECEPTOR MONOCLONAL ANTIBODY Type: Abstract Submission Topic: AS12 IMAGING – NON ACUTE INCLUDING NEUROSONOLOGY

L. Vinciguerra¹, V. Puglisi¹, E. Pari¹, C. Costanzi¹, A. Giossi¹, G. Lanza², M. Cantone³, R. Bella⁴ and B. Censori¹

¹ASST Cremona, Neurology, Cremona, Italy; ²University of Catania, Department of Surgery and Medical-Surgical Specialties, Catania, Italy; ³Sant’Elia Hospital, Neurology, Caltanissetta, Italy; ⁴University of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania, Italy

Background and Aims: Pathogenesis of migraine is believed to be neurogenic, with vascular changes having a role in the attack pathophysiology. Migraine patients have reported abnormalities in cerebral hemodynamics. Human monoclonal antibodies represent the new therapy of migraine, acting against the vasodilator effect of Calcitonin gene-related peptide. In this frame, the aim of the present study was to evaluate blood flow velocities in basal brain arteries and vasomotor reactivity of migraine patients using TCCD, before and after monoclonal antibody treatment with erenumab.

Methods: 11 patients with migraine without aura treated with erenumab were age-matched with 11 healthy controls. Peak Systolic Blood Flow Velocity (PSV), End-Diastolic Blood Flow Velocity, Mean Blood Flow Velocity (MBFV), Pulsatility Index, and Resistivity Index were recorded from the Middle Cerebral Artery (MCA) bilaterally and Basilar Artery. Cerebrovascular reactivity to breath-holding was also evaluated. Patients were evaluated at baseline, after 6 months from the first erenumab injection and after 1 year of treatment.

Results: A significant difference was observed in MBFV and PSV of the MCA in patients after 1 year of treatment with erenumab. In particular, patients exhibited a decrease in MBFV (p = 0.009) and PSV (p = 0.020) compared to controls.

Conclusions: Cerebral hemodynamics are partially changed in migraine patients after a long period of treatment with erenumab.

Trial Registration Number:

EPV0248 / #1789

Topic: AS14 CLINICAL PRACTICE, MANAGEMENT AND CARE

IMPACT OF THE COVID-19 PANDEMIC ON THE CLINICAL PRACTICE OF STROKES IN A REGION OF THE HEALTH SYSTEM OF SPAIN

J. Ramirez-Moreno^1,2, P. Macias Sedas², B. Rebollo², R. Hariramani², A. Roa², L. Fernandez Prudencio³, L. Fernandez De Alarcón³, M. Trinida³, N. Valverde², A. Constantino² and D. Ceberino²

¹Extremadura University School of Medicine, Biomedical Sciences, Badajoz, Spain; ²Universitary Hospital of Badajoz, Stroke Center. Neurology, Badajoz, Spain; ³Universitary Hospital of Badajoz, Stroke Center. Radiology, Badajoz, Spain

Background and Aims: There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively afects the quality of care for stroke. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workfow parameters of acute stroke care in our region.

Methods: The main variables of the study were: stroke admissions, reperfusion therapies, severity of stroke on admission, functional status at discharge, and mortality. Stroke registry data from February through December 2019 and 2020 were collected. For the analysis, all data were grouped by consecutive calendar weeks. We used Poisson regression models, Pearson correlation coefficient and univariate ARIMA time series modeling procedures and the spectral graphs procedure which is used to identify periodic time series.

Results: During the COVID-19 period, 319 patients presented with a suspected stroke compared to 407 patients in the 2019 period. Activity in stroke unit decreased compared to 2019. Ischemic stroke decreased by 14%, 289 vs. 248 (p = 0.101); hemorrhagic stroke by 36%, 50 cases vs 32 (p = 0.05) and transient ischemic attacks by 42%, 68 vs 39, (p = 0.012). The proportion of men was higher during the COVID-19 period ( p < 0.01). No differences were observed in the mean scores of NIHSS at admission in the periods. Thrombolytic therapy was reduced by 42% (p = 0.003). However, the mean number of weekly thrombectomies performed remained stable in those periods.

Conclusions: We observed a decrease in suspected stroke presentations during the COVID-19 outbreak, with impact in the quality of stroke care, with a reduction in fibrinolytic treatments and care for women.

Trial Registration Number: Not applicable.

EPV0250 / #1836

Topic: AS14 CLINICAL PRACTICE, MANAGEMENT AND CARE

SAFETY OF OFF-LABEL ORAL GLYBURIDE IN MALIGNANT HEMISPHERIC INFARCTIONS: A SINGLE-CENTER QUALITY IMPROVEMENT STUDY

M. Heslin¹, N. Vigilante¹, T. Yeager², T. Hester², J. Thon², L. Thau¹, A. Rana¹, R. Then², T. Jovin² and J. Siegler²

¹Cooper Medical School of Rowan University, Cooper Neurological Institute, Camden, United States of America; ²Cooper University Hospital, Neurology, Camden, United States of America

Background and Aims: Following the GAMES-RP trial, which showed intravenous glyburide can safely reduce cerebral edema following stroke, our center implemented a quality improvement initiative using off-label glyburide to prevent malignant cerebral edema in patients at risk.

Methods: Consecutive adults > 18 years of age with anterior circulation large hemispheric infarction at our center (9/20/2019–4/1/2021) were treated with off-label glyburide per an institutional protocol (2.5 mg PO BID × 3 days). We report the safety (discontinuation of drug due to hypoglycemia <50 mg/dL) and efficacy outcomes (midline shift, 90-day mRS) of patients as compared to the control arm of the GAMES-RP trial using a two-sample test of proportions.

Results: Thirty-six patients received glyburide (mean age of 66 years [SD 15], median NIHSS 20 [IQR 15-26], mean infarct volume on head CT of 104cc [SD 46]). Four patients developed hypoglycemia (11%) and 8 patients (22%) had the drug discontinued due to hypoglycemia concerns. Treated patients had numerically less midline shift when compared to historic controls (median 4 vs 8.5 mm). Comfort measures were pursued in 17 patients (57%), permitting long-term follow-up of 13 patients for whom the median 90-day mRS was 4 (IQR 3-5, n = 13).

Figure 8.

Conclusions: In this interim analysis, glyburide is associated with a low risk of significant hypoglycemia. Treated patients had severe deficits and large infarcts, approximately half of whom opted for comfort measures, with poor long-term functional outcomes among remaining patients. Notably, midline shift decreased by more than 50% compared to well-matched historic controls, and patients who opted for aggressive measures exhibited better 90-day functional outcomes.

EPV0282 / #2025

Topic: AS15 DIAGNOSIS/INVESTIGATION OF STROKE ETIOLOGY

PREDICTION OF ISCHEMIC STROKE ETIOLOGY USING NON-GATED CHEST SPECTRAL CT AFTER CEREBROVASCULAR CT ANGIOGRAPHY

J.J. Cirio¹, C. Ciardi¹, L. Caballero¹, C. Bleise², E. Scrivano², J. Lundquist², I. Lylyk², N. Perez², M. Ceron¹, P. Di Luca¹, G. Rodriguez-Granillo³ and P. Lylyk²

¹Clinica La Sagrada Familia-ENERI, Stroke Units, CAPITAL FEDERAL, Argentina; ²Insituto Medico ENERI-Clinica La Sagrada Familia, Neurointerventional Surgery, Bs As, Argentina; ³Clinica La Sagrada Familia-ENERI, Department Of Cardiovascular Imaging, CAPITAL FEDERAL, Argentina

Background and Aims: Delayed-phase, low-dose, non-gated, chest spectral CT scans (DSCT) has recently emerged as an alternative for the early triage of cardioembolic (CE) sources in patients with acute ischemic stroke (AIS). We explored the diagnostic performance of DSCT and the role of left atrium (LA) size in the prediction of the etiology.

Methods: Since July 2020, we implemented DSCT after cerebrovascular CTA in patients with AIS. We evaluated the presence of CE sources as well as late myocardium iodine enhancement (LIE), and we assessed LA size using different approaches.

Results: Eighty patients with AIS (median NIHSS 10) were included. There were no significant differences between groups regarding calcified coronary segments (non-CE 4.1 ± 3.6, CE 5.1 ± 3.6, ESUS 3.6 ± 3.7, p = 0.34), presence of significant LIE (non-CE 25%, CE 19%, ESUS 29%, p = 0.70), or extracellular volume (non-CE 0.33 ± 0.1, CE 0.34 ± 0.1, ESUS 0.36 ± 0.1, p = 0.26). Transesophageal echo/cardiac CT, performed in 26 (33%) patients, identified a CE source in 6 (23%) cases, whereas DSCT identified 4 (15%), leading to a sensitivity of 67%, a specificity of 100% [AUC 0.83]. The two disagreements comprised patients who underwent TEE 15 days and 30 days after DSCT. Albeit not achieving statistical significance, the LA area assessed by CT was the approach with the highest diagnostic performance for the identification of CE etiology [areaCT AUC 0.80, areaecho AUC 0.69, p = 0.21].

Conclusions: In this study, we demonstrated that DSCT enables a straightforward identification of CE sources upon admission, and offers a good estimate of LA size, which is related to AIS etiology.

EPV0283 / #2033

Topic: AS15 DIAGNOSIS/INVESTIGATION OF STROKE ETIOLOGY

EPICARDIAL AND PERIAORTIC FAT VOLUME AND DENSITY ACCORDING TO ISCHEMIC STROKE ETIOLOGY

J.J. Cirio¹, C. Ciardi¹, G. Bellizzi¹, M. Ceron², J. Lopez¹, M. Buezas¹, M. Chasco¹, C. Ingino³, P. Di Luca⁴, G. Rodriguez-Granillo² and P. Lylyk⁵

¹Clinica La Sagrada Familia-ENERI, Stroke Units, CAPITAL FEDERAL, Argentina; ²Clinica La Sagrada Familia-ENERI, Department Of Cardiovascular Imaging, CAPITAL FEDERAL, Argentina; ³Clinica La Sagrada Familia-ENERI, Department Of Cardiology, CAPITAL FEDERAL, Argentina; ⁴Clinica La Sagrada Familia-ENERI, Department Of Radiology, CAPITAL FEDERAL, Argentina; ⁵Clinica La Sagrada Familia-ENERI, Department Of Interventional Radiology, CAPITAL FEDERAL, Argentina

Background and Aims: Epicardial and periaortic fat have emerged as novel markers of adverse cardiovascular outcome. Furthermore, an increased fat density has been recently linked to inflammation and adverse events. We explored the relationship between acute ischemic stroke (AIS) etiology and epicardial and periaortic fat tissue.

Methods: We included patients admitted since 2012 with AIS in a comprehensive stroke center who also underwent a non-contrast chest CT scan within 1 month from admission. Three groups were discriminated according to the etiology; non-cardioembolic (non-CE), CE, and ESUS.

Results: Since 2012, a total of 185 patients admitted with AIS symptoms and without previous history of heart or vascular surgery had a non-contrast chest CT (non-CE, n = 66; CE, n = 64; and ESUS, n = 55). The mean age was 70.4 ± 13.7 years, with a trend towards older age among the CE group (p = 0.06). Coronary artery calcium score was similar between groups (p = 0.14) whereas aortic arch calcium score was significantly higher in the CE group (p = 0.025). Epicardial (non-CE 128.7 ± 46.9 cm3, CE 133.9±56.4 cm2, ESUS 121.6±63.5 cm2, p = 0.49) and periaortic (non-CE 37.3±18.3 cm3, CE 40.5±17.1 cm3, ESUS 34.5±14.1, p = 0.15) fat volume did not differ significantly between groups. However, epicardial (non-CE -76.8±12.9 HU, CE -73.0±6.4 HU, ESUS -76.3±6.7 HU, p = 0.052) and periaortic (non-CE -84.3±7.3 HU, CE -78.2±9.8 HU, ESUS -82.3±9.3 HU, p = 0.001) fat density levels were higher in patients with CE etiology.

Conclusions: In this study, epicardial and periortic fat density levels of patients with CE stroke were higher than non-CE and ESUS etiologies, suggesting underlying inflammation.

EPV0304 / #1497

Topic: AS16 PROGNOSIS AND OUTCOME AFTER STROKE

COMPARISON OF THE SOLUBLE FIBRIN-MONOMER COMPLEXES STUDY RESULTS WITH A FAVORABLE AND FATAL OUTCOME OF CARDIOEMBOLIC STROKE ON THE BACKGROUND OF NON-VALVULAR ATRIAL FIBRILLATION

V. Mishchenko¹, T. Mishchenko¹, K. Kharina¹ and V. Bokatuieva¹

¹Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine., Department Of The Brain Vascular Pathology And Rehabilitation, Kharkiv, Ukraine

Background and Aims: Cardioembolic stroke occurs in 22-39% of all ischemic stroke cases. This type of ischemic stroke is characterized by fibrinolytic and hemorheological changes. Soluble fibrin-monomer complexes (SFMC) test is often used in clinical practice for the treatment and diagnosis of cardioembolic stroke. This test is a marker of thrombinemia in intravascular coagulation.

Methods: The SFMC level was examined in 69 men with cardioembolic stroke. 46 men had a favorable outcome and 23 men had a fatal outcome of treatment. The results were processed using IBM SPSS Statistics 20 using the χ2 criterion.

Results: The study of SFMC level in male patients with favorable disease outcomes showed that patients older than 61 years had significantly (p < 0.05) higher incidence of increased SFMC levels than patients with normal level of this indicator.In the group of deceased male patients, the incidence of increased SFMC level was significantly (p < 0.05) higher than in patients with normal SFMC values in the age groups 51-60, and older 71 years. Note: 1 – differences in the frequency of SFMC level in the range (0-4) and over 4 in the corresponding age group are significant by the criterion χ2 (p < 0.05).

Conclusions: An increased SFMC level may be one of the indicators pointing at adverse outcome of cardioembolic stroke.

Trial Registration Number: Not applicable.

EPV0385 / #835

Topic: AS21 RARE CAUSES, STROKE IN THE YOUNG

CLINICAL AND RADIOLOGICAL FEATURES OF CVST PATIENTS PRESENTING ISOLATED SAH OR HEMORRHAGIC INFARCTION

J. Kobal¹, K. Cankar², B. Vudrag¹ and K. Ivanušič³

¹UMC Ljubljana, Neurology, Ljubljana, Slovenia; ²Medical Faculty Ljubljana, Physiology, Ljubljana, Slovenia; ³UMC Ljubljana, Radiology, Ljubljana, Slovenia

Background and Aims: Central venous thrombosis (CVT) is a rare cerebral vascular disease and that represents 0.5-1% of all strokes. Presentation of CVT is highly variable clinically and radiologically. A recent study showed that isolated subarachnoid hemorrhage (SAH) is not so rare and has a good prognostic significance. It seems however that hemorrhagic infarction is a factor of unfavorable outcome and is associated to multiple sinuses/veins occlusion. We hypothesized that our patients who initially suffered isolated SAH will have a better clinical outcome than those who suffered hemorrhagic cerebral infarction.

Methods: We chose the patients hospitalized due to CVST and presented either isolated SAH or cerebral hemorrhagic infarction at admission time or during the next 24 hours. They were 12 women and 9 men aged 22-73 years. The data was extracted from hospital admission records, our computer data system and radiological database system.

Results: The isolated SAH group were 6 (5 men) aged 49.4 ± 17.5 and hemorrhagic infarction group were 15 (11 women) aged 48.3 ± 17.3. The isolated SAH group had significantly better outcome regarding mRS score than hemorrhagic infarction group (Mann-Whitney Rank Sum Test, p = 0.019) despite significantly greater number of thrombosed venous sinuses/deep veins. (Mann-Whitney Rank Sum Test, p = 0.003). Additional variable with significant impact was space occupying lesions that were absent in our isolated SAH group.

Conclusions: We conclude that patients who suffer isolated SAH initially have significantly better outcome prognosis than hemorrhagic infarction patients despite greater number of thrombosed sinuses. A possible explanation might include patent superficial communicating veins.

EPV0428 / #1503

Topic: AS25 SMALL VESSEL DISEASE

NIGHT SLEEP STRUCTURAL ORGANIZATION VIOLATIONS AS A PREDICTOR OF AN UNFAVORABLE COURSE OF THE CEREBRAL SMALL VESSEL DISEASE

L. Zabrodina¹, V. Mishchenko², T. Mishchenko², J. Bovt² and V. Sukhorukov¹

¹State Institution "Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine", Sleep Medicine Department, Kharkiv, Ukraine; ²Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine., Department Of The Brain Vascular Pathology And Rehabilitation, Kharkiv, Ukraine

Background and Aims: Questions of finding additional informative progression markers of cerebral small vessel disease (CSVD) determined the need for this study. Aim. Night sleep structure analysis in patients with CSVD and allocation of its neurophysiological markers of unfavorable clinical course.

Methods: 28 patients of both sexes aged 54.8 ± 2.1 years with CSVD, confirmed by magnetic resonant imaging was surveyed. All patients were carried out polysomnography (PSG).

Results: We identified the groups of patients with favorable (group 1 - 17 patients) and unfavorable (groups 2 - 11 patients) course of CSVD. Group 2 patients had more pronounced neurological symptoms and frequent decompensations. Table 1. PSG idicators of favorable and unfavorable disease course of CSVD

Group 2 patients were reliably more sleeping time, less than the non-rapid eye movement (NREM) stage duration and delta-sleep, as well as less duration and number of episodes rapid eye movement (REM) stage. It was revealed that these patients in the structure of night sleep increases the number of unfinished sleep cycles with a statistically significant reduction in the number of completed cycles, which indicates the integrity violation of the cyclic sleep organization and is a negative neurophysiological criteria.

Conclusions: Violation of the night sleep structural organization can lead to the CSVD progression, which increases the risk of brain stroke.

Trial Registration Number: Not applicable.

Figure 9.

EPV0579 / #674

Topic: AS33 CASE REPORTS

CAROTID WEB AS A RARE CAUSE OF ISCHEMIC STROKE: CASE REPORT AND LITERATURE REVIEW

E. Spina¹, G. Palmieri², M. Marseglia³, F. Manganelli₂ and F. Briganti³

¹University of Naples, Department Of Neurosciences, Reproductive And Odontostomatology, Naples, Italy; ²University of Naples "Federico II", Deparment Of Neurosciences, Reproductive And Odontostomatology, Naples, Italy; ³University of Naples "Federico II", Department Of Advanced Biomedical Sciences, Naples, Italy

Background and Aims: Carotid web (CW) is a thin, intraluminal, diaphragm-like intimal strip of tissue that is projected from the wall of the carotid artery and it can be an underestimated cause of ischemic stroke.

Methods: We reported on a 65-year-old African man presenting with acute-onset right-hand palsy and wrist drop with subacute left prerolandic, middle frontal, and superior parietal ischemic areas.

Results: Extensive diagnostic workup did not detect common possible causes of stroke. Bilateral CW was detected on Duplex Ultrasound as membrane-like structure along the posterior wall of carotid bulb protruded into the lumen and confirmed on TC-Angiography. Symptomatic side CW underwent stenting procedure, with no periprocedural adverse events.

Conclusions: CW could be a rare cause of recurrent ischemic stroke with abrupt onset left-hand palsy and re-stroke with left facial palsy. Stenting followed by 3-months DAPT and then long-term antiplatelet therapy is a satisfactory alternative to treat those patients.

Trial Registration Number: not applicable.

EPV0520A / #572

Topic: AS36 ONGOING TRIALS

A RANDOMIZED CONTROLLED TRIAL TO TEST EFFICACY AND SAFETY OF THROMBECTOMY IN STROKE WITH EXTENDED LESION AND EXTENDED TIME WINDOW (TENSION)

S. Bonekamp¹, M. Bendszus², A.H. Aamodt³, F. Boutitie⁴, P. Brouwer⁵, J. Fiehler⁶, B. Fuentes Gimeno⁷, E. Gizewski⁸, A. Krajina⁹, L. Pierot¹⁰, G. Randall¹¹, C. Simonsen¹², K. Zeleňák¹³, G. Thomalla¹⁴; The Tension Trial Investigators

¹University Hospital Heidelberg, Neuroradiology, Heidelberg, Germany; ²Heidelberg University Hospital, Neuroradiology, Heidelberg, Germany; ³Oslo University Hospital, Department Of Neurology, Oslo, Norway; ⁴Centre Hospitalier Lyon Sud, Service De Biostatistique, Pierre-Bénite, France; ⁵Karolinska Universitetssjukhuset, Neuroradiologiska Kliniken, Stockholm, Sweden; ⁶University Medical Center Hamburg Eppendorf, Neuroradiology, Hamburg, Germany; ⁷Hospital Universitario La Paz, Servicio De Neurología Y Centro De Ictus, Madrid, Spain; ⁸University Hospital Inssbruck, Univ. Klinik Für Neuroradiologie, Innsbruck, Austria; ⁹CHARLES UNIVERSITY, Dept. Of Radiology, Hradec Kralove, Czech Republic; ¹⁰Centre hospitalo-universitaire Reims Université Reims Champagne Ardenne, Neuroradiology, Reims, France; ¹¹Stroke Alliance for Europe (SAFE), Eu Research Manager, Brussels, Belgium; ¹²Aarhus Universitetshospital, Department Of Neurology, Aarhus, Denmark; ¹³Comenius University’s JesseniusFaculty of Medicine and University Hospital, Department Of Radiology, Martin, Slovak Republic

Background and Aims: The benefit of thrombectomy in patients with large intracranial vessel occlusion of the anterior circulation has been shown in selected patients in previous randomized controlled trials, but patients with extended stroke lesions were excluded in the majority of these trials. TENSION aims to demonstrate efficacy and safety of thrombectomy in patients with extended stroke lesions in an extended time window or unknown stroke onset.

Methods: TENSION is an investigator-initiated, prospective, open label, blinded endpoint (PROBE), European, two-arm, randomized, controlled, post-market study to compare the safety and effectiveness of thrombectomy as compared to best medical care alone in stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early CT Scan score (ASPECTS) of 3-5 and in an extended time window (up to 12 hours, or unknown time of symptom onset). In an adaptive design study, up to 665 patients will be randomized.

Results: Primary efficacy endpoint will be clinical outcome defined by the modified Rankin Scale (mRS) at 90 days post-stroke. The main safety endpoint will be death and dependency (mRS 4-6) at 90 days. Additional measures include adverse events, functional health status, post-stroke depression and costs utility assessment. The trial started randomizing in July 2018. We will present current site activation and enrollment numbers.

Conclusions: TENSION will provide evidence for effective treatment for severe stroke patients thereby improving functional outcome and quality of life of thousands of stroke patients.

Trial Registration Number: TENSION is registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT03094715).

EPV0577A / #656

Topic: AS36 ONGOING TRIALS

OMEGA3 AND ACUTE OCCLUSIVE ISCHEMIC STROKE PATIENTS: EXPECTED PROMISING TREATMENT

W. Alkassas¹, N. Al Mansour² and A. Eltaher³; Nouf Ali Mohammed Al MansourWesam Alkassas Ahmed Mamdoh Nahed Yosef Lubbad

¹Dr Sulaiman Alhabib Hospital, Internal Medicine, Buraidah, Saudi Arabia; ²King Fahd Medical City, Stroke Unit Adult Neurology, Riyadh, Saudi Arabia; ³Sulaiman Alrajhi University, Mbbs, Qassim, Saudi Arabia

Background and Aims: Background Several studies have examined the relation between stroke and the intake of omega-3 polyunsaturated fatty acid (PUFA) intake. These studies have looked into connections such as the effect on stroke incidence and on functional outcomes. However, many of these studies were non-conclusive. In addition, none of these studies have attempted to examine the anti-neuroinflammatory effect of PUFA on human neurogenesis in the acute phase and how it can affect and reduce the size of the infarcted area after ischemic stroke like several animal trials found recently. Objectives of the trial: To examine the effect of omega-3 polyunsaturated fatty acid intake on: - The size of change of the infarcted area after an acute ischemic stroke and reperfusion. -Functional outcomes after an acute ischemic stroke and reperfusion. - Tolerence of Omega-3 to this group.

Methods: The study will be a placebo, open-labelled two-armed RCT, phase 4. One arm will receive the intervention (fish oil). The other arm will be receiving the placebo. The subjects of this study will round up to 60 ischemic, non-hemorrhagic, reprefused, and non-complicated stabilized stroke patients admitted to ASU and NCCU.

Results: Expected Outcomes We expect to a decrease in area of infarction after 1 month of intervention omega-3 polyunsaturated fatty acid intake and 3 months of follow up, which in consequence will hopefully lead to an improved functional outcome. Improving the repercussions of surviving a stroke will not only improve the quality of life for the patients but also for their families.

Conclusions: Not Applicable (on goning trial).

Trial Registration Number: Ethical approval form King Fahd Medical CityRiyadhSaudi Arabia: IRB Log Number 20-310 NIH ClinicalTrials.gov Identifier: NCT04386525.

EPV0612B / #794

Topic: AS36 ONGOING TRIALS

STUDY IN NOVEL NEURO-MUSCULAR IMAGING BIOMARKERS FOR MOTOR OUTCOME IN STROKE

H. Lumley¹, M. Elameer^1,2, C. Price^1,3, S. Moore^4,5, A. Gani⁶, F. Smith⁷, P. English², A. Blamire⁷ and D. Mitra^1,2; Stroke Research Group

¹Newcastle University, Population Health Sciences Institute, Newcastle upon Tyne, United Kingdom; ²Newcastle upon Tyne Hospitals NHS Foundation Trust, Neuroradiology, Newcastle upon Tyne, United Kingdom; ³Northumbria Healthcare NHS Foundation Trust, Stroke, Newcastle upon Tyne, United Kingdom; ⁴Northumbria University, Physiotherapy, Newcastle upon Tyne, United Kingdom; ⁵Northumbria Healthcare NHS Foundation Trust, Physiotherapy, Newcastle upon Tyne, United Kingdom; ⁶Newcastle upon Tyne Hospitals NHS Foundation Trust, Stroke, Newcastle upon Tyne, United Kingdom; ⁷Newcastle University, Translational And Clinical Research Institute, Newcastle upon Tyne, United Kingdom

Background and Aims: Lower-limb impairment is common after stroke, limiting independence of those affected. Early, accurate prediction of recovery could enable individualised rehabilitation and optimise outcomes. Previous evidence supports an effect of stroke-related damage to cortico-spinal tracts (CST) on functional recovery. However, effects of post-stroke sarcopenia, resultant muscle fiber-type shift and inflammation are unknown. An algorithm accounting for these changes, based on combined MRI imaging of the source-organ (brain) and end-organ (lower-limb skeletal muscle), may have superior accuracy compared with clinical assessments or isolated MRI biomarkers. We aim to assess the feasibility and utility of MRI biomarkers for predicting lower-limb recovery following stroke.

Methods: 30 patients will be recruited from two North-East England NHS trusts within 4 weeks of their first-ever ischaemic stroke causing unilateral lower-limb weakness. Patients undergo brain and thigh muscle MRI, including volumetric sequences, lipid and oedema-based muscle imaging and diffusion tensor imaging of the CST. This is followed by baseline and 3-month clinical assessments of: lower-limb impairment (Fugl-Meyer; Motor NIHSS) strength (handheld-dynamometry) and function (Functional Ambulatory Category).

Results: 12/30 participants have been recruited since 2019 and the study will close in 2022. Correlations between MRI, clinical and 3-month follow-up outcome data will assess relationships between biomarkers and outcomes to inform a predictive model incorporating baseline clinical and MRI data.

Conclusions: This project will provide novel data on sarcopenia-based measures in stroke. If our model has predictive value, a sample size estimate will be calculated to inform future multicentre studies with the aim of developing a robust predictive algorithm.

Trial Registration Number: ISRCTN 14822732.

EPV0580A / #831

Topic: AS36 ONGOING TRIALS

APIXABAN FOR TREATMENT OF EMBOLIC STROKE OF UNDETERMINED SOURCE - ATTICUS RANDOMIZED TRIAL- UPDATE OF PATIENT CHARACTERISTICS AND STUDY TIMELINE AFTER INTERIM ANALYSIS

S. Poli¹, C. Meisner², A. Mengel¹, H. Baezner³, M. Wolf³, A. Kraft⁴, F. Hoffmann⁴, F. Hillenbrand⁵, L. Niehaus⁵, C. Hobohm⁶, J. Liman⁷, R. Wachter⁸, H. Kimmig⁹, W. Jung¹⁰, R. Huber¹¹, A. Lindner¹², K. Althaus¹³, J. Meyne¹⁴, M. Schabet¹⁵, G. Petzold¹⁶, J. Brachmann¹⁷, M. Ebinger¹⁸, M. Gawaz¹⁹, U. Ziemann¹, T. Geisler¹⁹; ATTICUS investigators

¹University Hospital Tübingen, Neurology & Stroke, Tübingen, Germany; ²Eberhard-Karls University of Tübingen, Biometry, Tübingen, Germany; ³Klinikum Stuttgart, Neurology, Stuttgart, Germany; ⁴Hospital Martha-Maria Halle Dölau, Neurology, Halle, Germany; ⁵Rems-Murr-Clinic, Neurology, Winnenden, Germany; ⁶Carl-von-Basedow-Clinic Saalekreis, Neurology, Merseburg, Germany; ⁷University Medicine Goettingen, Neurology, Göttingen, Germany; ⁸University of Leipzig, Cardiologie, Leipzig, Germany; ⁹Schwarzwald-Baar Hospital, Neurology, Villingen-Schwenningen, Germany; ¹⁰Schwarzwald-Baar Hospital, Cardiology, Villingen-Schwenningen, Germany; ¹¹Medical Campus Lake Constance, Neurology, Friedrichshafen, Germany; ¹²Marien Hospital, Neurology, Stuttgart, Germany; ¹³University Hospital Ulm, Neurology, Ulm, Germany; ¹⁴University Hospital Kiel, Neurology, Kiel, Germany; ¹⁵Ludwigsburg Hospital, Neurology, Ludwigsburg, Germany; ¹⁶University Hospital Bonn, Neurology, Bonn, Germany; ¹⁷Regiomed Clinic Coburg, Neurology, Coburg, Germany; ¹⁸Charité–Universitätsmedizin Berlin, Germany, Center For Stroke Research Berlin, Berlin, Germany; ¹⁹University Hospital Tübingen, Cardiology, Tübingen, Germany

Background and Aims: Secondary prevention after ESUS has not yet been established. ESUS is associated with high risk of recurrent ischemic stroke. Aspirin (ASA) is the current standard after ESUS, despite high prevalence of occult atrial fibrillation (AF). To determine whether apixaban, started ≤28 days after ESUS, is superior to ASA in preventing new ischemic lesions on 12-month FLAIR/DWI (primary endpoint) in subjects with remote cardiac monitoring.

Methods: ATTICUS enrolled ESUS patients with at least one risk factor for cardiac thromboembolism (i.e., left atrium (LA) size >45 mm, spontaneous echo contrast in LA appendage, LA appendage flow velocity ≤0.2 cm/s, atrial high-rate episodes, CHA2DS2-Vasc ≥4, patent foramen ovale). 1:1 randomization. Study drug initiation 3–28 days after minor/moderate stroke and ≥14–28 days after major stroke. ClinicalTrials.gov: NCT02427126. Funding: ATTICUS is supported by BMS-Pfizer Alliance.

Results: Enrollment stopped after interims analysis (n = 200) due to futility. 373 patients screened; 178/175 apixaban/ASA enrolled. So far, 250 subjects completed the study: 68.5 years, 51% males, 80% hypertension, CHA2DS2-VASc 4.9. 63% adverse events, 30% severe, 2% death. 6.8% recurrent ischemic, no hemorrhagic stroke. Only 1 severe bleeding in ASA arm. 23% new AF. Due to ongoing data clearing, numbers/% will change until presentation.

Conclusions: In contrast to NAVIGATE and RESPECT ESUS, patients enrolled in ATTICUS need to exhibit AF predicting factors. Furthermore, mandatory cardiac remote monitoring will help to elucidate AF impact and effects of early oral anticoagulation with apixaban versus ASA on incidence of new ischemic lesions after ESUS. Preliminary data will be presented and discussed in context of current literature.

Trial Registration Number: ClinicalTrials.gov Identifier: NCT02427126.

EPV0583A / #843

Topic: AS36 ONGOING TRIALS

FOCAS: FOLLOW-UP IN SPORADIC CEREBRAL AMYLOID ANGIOPATHY STUDY

S. Voigt¹, K. Kaushik¹, I. Rasing¹, E. Koemans¹, T. Van Harten², E. Van Etten¹, M. Verbeek³, M. Van Buchem², S. Van Rooden⁴, J. Van Der Grond², E. Van Zwet⁵, M. Van Walderveen², M. Van Osch², G. Terwindt¹ and M. Wermer¹

¹Leiden University Medical Center, Department Of Neurology, Leiden, Netherlands; ²Leiden University Medical Center, Radiology, Leiden, Netherlands; ³Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department Of Neurology, Nijmegen, Netherlands; ⁴Leiden University Medical Center, Clinical Genetics, Leiden, Netherlands; ⁵Leiden University Medical Center, Biomedical Data Sciences, Leiden, Netherlands

Background and Aims: The disease course of sporadic Cerebral Amyloid Angiopathy (sCAA) varies widely. Some patients have only one intracerebral hemorrhage (ICH) whereas others experience multiple recurrences. For some, the disease course can be characterized by rapid cognitive decline or frequent headaches and seizures, whereas in others, sCAA has a relatively mild symptomatology. Except for APOE genotype and hypertension, it is unknown which factors affect the disease course. The objective of this follow-up study is to investigate clinical risk factors and MR markers of disease progression, thereby gaining more insight in diagnosis, prevention and therapy of sCAA.

Methods: In all patients, baseline and follow-up 3T-MRI (yearly) and 7T-MRI (2-yearly) will be performed over a period of 6 years. The standardized annual study protocol consists of an interview (general health and vascular risk factors), neurological examination, cognitive screening and blood withdrawal. Participants will be asked for a lumbar puncture each study visit. Both blood and cerebrospinal fluid will be stored for future biomarker analysis. Electroencephalography and home blood pressure monitoring will be performed once during follow-up.

Results: Main study parameters are: CAA markers on 3T-MRI and 7T-MRI, changes in CSF and plasma, ICH recurrence rate and clinical outcome. We will investigate disease progression in 50 sCAA patients and 20 mixed-type pathology patients, and compare with a population of (pre)symptomatic Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation carriers (AURORA study, analogous protocol).

Conclusions: Current status: FOCAS started in May 2018, to date 50 patients have been included.

Trial Registration Number: Not applicable.

EPV0585A / #902

Topic: AS36 ONGOING TRIALS

PREVENTION OF DEMENTIA USING MOBILE PHONE APPLICATIONS (PRODEMOS) - A MULTINATIONAL RANDOMIZED CONTROLLED TRIAL IN PROGRESS

M. Hafdi¹, E. Moll Van Charante², M. Hoevenaar-Blom^2,3, S. Andrieu⁴, E. Eggink², P. Witvliet², N. Coley⁴, A. Wimo⁵, L. Barnes⁶, R. Brooks⁶, R. Handels⁵, M. Song⁷, J. Georges⁸, R. Mast⁹, Y. Wang⁷, W. Wang⁷, W. Van Gool¹⁰, C. Brayne¹¹, E. Richard^10,12; on behalf of the PRODEMOS consortium

¹Amsterdam UMC, location AMC, Neurology, Amsterdam, Netherlands; ²Amsterdam UMC, Public And Occupational Health, Amsterdam, Netherlands; ³Amsterdam University Medical Center, location AMC, Neurology, Amsterdam, Netherlands; ⁴INSERM-University of Toulouse UMR 1295, Centre For Epidemiology And Research In Population Health (cerpop), Toulouse, France; ⁵Karolinska Institutet, Center For Alzheimer Research, Stockholm, Sweden; ⁶Cambridge Institute of Public Health, Department Of Public Health And Primary Care, Cambridge, United Kingdom; ⁷Capital Medical University, School Of Public Health, Beijing, China; ⁸Alzheimer Europe, Alzheimer Europe, Luxembourg, Luxembourg; ⁹Philips VitalHealth, Philips Vitalhealth, Ede, Netherlands; ¹⁰Amsterdam University Medical Center, location AMC, Department Of Public And Occupational Health, Amsterdam, Netherlands; ¹¹University of Cambridge, Department Of Public Health And Primary Care, Cambridge, United Kingdom; ¹²Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department Of Neurology, Nijmegen, Netherlands

Background and Aims: The rising prevalence of dementia will largely occur in low- and middle-income countries. Mobile Health (mHealth) can improve accessibility to prevention and facilitate self-management. We aim to investigate whether optimization of dementia risk factors using an interactive mHealth intervention leads to reduction of risk of dementia, cardiovascular disease and stroke and to evaluate implementation of the intervention.

Methods: Participants are randomized to a coach-supported, interactive mHealth platform facilitating self-management of dementia risk factors (including hypertension, diabetes, dyslipidemia, physical inactivity, smoking, poor diet, overweight) or to a control platform with static health information. People are eligible if they are 55-75 years, of low socio-economic status (UK) or from the general population (China), have ≥2 dementia risk factors, and are in possession of a smartphone. The intervention and follow-up will be 12-18 months.

Results: The study logistics and mHealth platform have been tested in a 6-week pilot study (n = 21 in UK, n = 56 in China), demonstrating the feasibility of the intervention. The prospective open-label blinded endpoint (PROBE) RCT is currently enrolling 2400 participants in the United Kingdom (n = 1200) and in China (n = 1200). The primary effectiveness outcome is dementia risk as measured by the CAIDE risk score. Main secondary outcomes are improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility, fidelity and sustainability of the intervention.

Conclusions: The current study, targeting populations with a high dementia risk and poor access to preventive care, may provide proof-of-principle for the implementation potential and effectiveness of a coach-supported mHealth intervention to reduce the risk of dementia.

Trial Registration Number: ISRCTN15986016.

EPV0591A / #1005

Topic: AS36 ONGOING TRIALS

LEFT ATRIAL APPENDAGE OCCLUSION FOR AF PATIENTS AT HIGH STROKE RISK UNABLE TO USE ORAL ANTICOAGULATION THERAPY: DESIGN AND RATIONALE OF THE COMPARE LAAO TRIAL

M. Huijboom¹, E. Aarnink¹, M. Maarse¹, V. Van Dijk¹, M. Swaans¹, L. Boersma¹; On behalf of the COMPARE LAAO Trial Investigators

¹St. Antonius Hospital, Cardiology, Nieuwegein, Netherlands

Background and Aims: Left atrial appendage occlusion (LAAO) for stroke prevention is increasingly performed in patients with atrial fibrillation (AF) and contraindications for oral anticoagulants (OAC). Although RCT data suggest that LAAO may provide a non-inferior alternative to OAC, RCT data on OAC-ineligible patients is lacking. The purpose of this study is to assess the efficacy and safety of LAAO. The two co-primary efficacy endpoints are time to first occurrence of stroke (ischemic, haemorrhagic or undetermined) and time to first occurrence of the composite of all-cause stroke, TIA and systemic embolism. The primary safety endpoint is the 30-day rate of procedural complications.

Methods: This is a multicentre, prospective RCT. Patients with AF and a CHA2DS2-VASc score ≥ 2 (women ≥ 3) with a long-term contraindication for OAC, determined by a multidisciplinary team, will be randomized in a 2:1 fashion to the device- or control arm. The device arm receives post procedural antiplatelet therapy (APT) per protocol, the control arm continues their current treatment that includes no therapy or (D)APT as deemed appropriate by the referring physician. In this endpoint driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, follow-up of 609 patients is minimal one- and maximum 5 years. Cost-effectiveness analysis will be performed to determine the budget impact in the Dutch Healthcare system.

Results: Are expected toward the end of 2026.

Conclusions: The COMPARE LAAO trial investigates the superiority and cost-effectiveness of LAAO in AF patients at high thromboembolic risk unable to use OAC due to absolute contraindications.

Trial Registration Number: NCT trial number: NCT04676880.

EPV0334A / #1414

Topic: AS36 ONGOING TRIALS

EFFECTS OF AN AVOCADO BASED MEDITERRANEAN DIET ON SERUM LIPIDS FOR SECONDARY PREVENTION AFTER ISCHEMIC STROKE TRIAL (ADD-SPISE)

V. Olavarria¹, P. Campodonico² and P. Lavados¹

¹Clinica Alemana de Santiago, Neurology And Psychiatry, Santiago, Chile; ²Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Centro De Quimica Medica, Icim, Santiago, Chile

Background and Aims: Background: Dietary risk has a high impact in DALYs in acute ischemic stroke (AIS). Adherence to dietary patterns like the Mediterranean Diet (MeDi) are associated with a decreased risk of stroke mortality/incidence in observational studies and primary prevention trials. Furthermore, lowering Low Density Cholesterol (LDL-C) levels decreases stroke recurrence. Interestingly, Avocado-substituted diets significantly decrease cholesterol levels. Aim: To investigate the effect of a MeDi based on Avocados on lipid profile after an AIS.

Methods: and patients: Academic, open-label, blinded outcome assessment, controlled clinical trial. Recruitment within a month of AIS if fulfilling eligibility criteria (including consent) and randomly assigned to the diet intervention in a 1:1 ratio. Intervention: (A) Avocado based MeDi with daily intake of ½ an avocado (B) Low fat-high complex carbohydrate healthy-diet. Study outcomes: Main outcome: Level of plasma LDL-C at 3 months of intervention. Secondary outcomes: Levels of lipid profile, inflammation markers, glycemic control, anthropometric measures, stroke recurrence, cardiovascular events, adverse events, compliance. Sample size estimates: A sample of 200 patients was estimated to provide 80% power and 5% level of significance (10% loss and 5% crossover) to detect a 4.6 ml/dL difference of in LDL-C. The study has ethics committee approval.

Results: Trial status: The trial is progressing as planned. From August 2018 to March 2021, 113 patients have been recruited and 81 have completed 3-month follow-up.

Conclusions: We hypothesize that an Avocado based MeDi will significantly reduce levels of LDL-cholesterol at 3 months in patients who have suffered an AIS compared to the control diet.

Trial Registration Number: Clinical Trials.gov Identifier NCT03524742.

EPV0513A / #1483

Topic: AS36 ONGOING TRIALS

SECRET - STUDY OF RIVAROXABAN IN CEREBRAL VENOUS THROMBOSIS

V. Dizonno¹, K. Villaluna¹, M. Hill², T. Field¹; On behalf of the SECRET and TOP-SECRET Investigators

¹University of British Columbia, Neurology, Vancouver, Canada; ²University of Calgary, Department Of Clinical Neurosciences, Calgary, Canada

Background and Aims: Cerebral venous thrombosis (CVT) is a rare cause of stroke that primarily affects the young. Although up to 85-90% of survivors have an “excellent” functional outcome (mRS 0-1), there may be persistent symptoms (eg. headache, fatigue, cognitive issues) affecting quality of life in up to 60%. The optimal antithrombotic strategy is unknown. NOACs may be an appropriate antithrombotic strategy for CVT due to superior safety, convenience and decreased length of hospital stay.

Methods: Randomized PROBE-design pilot trial and parallel registry Pilot trial: 50 individuals presenting with CVT, randomized to rivaroxaban 20 mg daily vs. standard of care within 14 days of diagnosis. Minimum 180 days of treatment. Registry: enrolment will continue until trial is complete. Same schedule of evaluations. AIMS Primary (Trial) - Feasibility: Feasibility of recruitment. Secondary (Trial) - Safety: Rates of all-cause mortality, symptomatic intracranial bleeding and major extracranial bleeding at 180 days Secondary: Multiple outcomes including mRS, headache, fatigue, cognition, mood, health care utilization at day 365.

Results: Vancouver launched March 2019 12 sites active as of January 2020. 1 additional site with start-up in progress SECRET: 42 enrolled as of April 2021 TOP-SECRET: 37 enrolled as of April 2021 Inaugural patient engagement forum January 2019.

Figure 10.

Conclusions: ANTICIPATED IMPACT Creating a framework for conducting high-quality clinical trials for CVT Generating safety data for NOACs in CVT Prospectively ascertaining prognostic data on CVT using outcomes beyond the mRS that are impactful for patients Developing a network of survivors and supporters for a rare cause of stroke.

Trial Registration Number: https://clinicaltrials.gov/ct2/show/NCT03178864.

EPV0259B / #1775

Topic: AS36 ONGOING TRIALS

AURORA: DUTCH-TYPE HEREDITARY CEREBRAL AMYLOID ANGIOPATHY NATURAL HISTORY STUDY

I. Rasing¹, S. Voigt¹, E. Koemans¹, K. Kaushik¹, T. Van Harten², E. Van Etten¹, M. Verbeek³, M. Van Buchem², S. Van Rooden⁴, J. Van Der Grond², E. Van Zwet⁵, M. Van Walderveen², M. Van Osch², G. Terwindt¹ and M. Wermer¹

¹Leiden University Medical Center, Neurology, Leiden, Netherlands; ²Leiden University Medical Center, Radiology, Leiden, Netherlands; ³Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department Of Neurology, Nijmegen, Netherlands; ⁴Leiden University Medical Center, Clinical Genetics, Leiden, Netherlands; ⁵Leiden University Medical Center, Biomedical Data Sciences, Leiden, Netherlands

Background and Aims: Dutch-type hereditary cerebral amyloid angiopathy (D-CAA, also known as HCHWA-D), is an autosomal dominant form of cerebral amyloid angiopathy (CAA) caused by a mutation in the amyloid-beta (Aβ) precursor protein gene. Because of pathological and biochemical similarities, D-CAA is considered to be a monogenic model for sporadic CAA (sCAA). Though the disease course varies widely, disease onset is approximately 20 years earlier in D-CAA than in sCAA patients. This wide variation in phenotype suggests that additional systemic factors may interact with amyloid in triggering ICH. The aim of this prospective follow-up study is to investigate the (pre)symptomatic disease course and to assess clinical risk factors and biomarkers of disease progression.

Methods: In all patients, baseline and follow-up 3T-MRI (yearly) and 7T-MRI (2-yearly) will be performed over a period of 6 years. The standardized annual study protocol consists of an interview (general health and vascular risk factors), neurological examination, cognitive screening and blood withdrawal. Participants will be asked for a lumbar puncture each study visit. Blood and cerebrospinal fluid will be stored for future biomarker analysis. Electroencephalography and home blood pressure monitoring will be performed once during follow-up.

Results: Main study parameters: CAA markers on 3T-MRI and 7T-MRI, changes in CSF and plasma, ICH recurrence rate and clinical outcome. We will investigate disease progression in 150 (pre)symptomatic mutation carriers and compare D-CAA patients with the sCAA population (FOCAS study, analogous protocol).

Conclusions: Current status: AURORA started in May 2018, until now 83 patients have been included.

Trial Registration Number: Not applicable.

EPV0261A / #1782

Topic: AS36 ONGOING TRIALS

ACTION: ANAKINRA IN CEREBRAL HAEMORRHAGE TO TARGET SECONDARY INJURY RESULTING FROM NEUROINFLAMMATION – A PHASE II CLINICAL TRIAL

M. Cliteur¹, J. Hofmeijer², H. Den Hertog³, K. Klijn¹ and F. Schreuder¹

¹Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department Of Neurology, Nijmegen, Netherlands; ²Rijnstate, Neurology, Arnhem, Netherlands; ³Isala Hospital, Neurology, Zwolle, Netherlands

Background and Aims: Background: Inflammation plays a vital role in the development of secondary brain injury after spontaneous intracerebral haemorrhage (ICH). Interleukin-1 beta is an early pro-inflammatory cytokine and a potential therapeutic target. Objectives: To estimate the safety and efficacy of treatment with recombinant human interleukin-1 receptor antagonist anakinra compared to standard medical management, and whether its effects are dose-dependent.

Methods: Study design: Phase-II, prospective, randomized, three-armed (1:1:1) trial with open-label treatment and blinded end-point assessment at three hospitals in the Netherlands. Study population: 75 patients with supratentorial spontaneous ICH admitted within 8 hours after symptom onset will be included. Intervention: Participants will receive standard medical management and anakinra in a high dose (loading dose 500 mg intravenously, followed by infusion with 2 mg/kg/h over 3 days; n = 25) or low dose (loading dose 100 mg subcutaneously, followed by subcutaneous administration of 100 mg twice a day for 3 days; n = 25). The control group (n = 25) will receive standard medical management alone. Sample size: A sample size of 25 participants per group allows to detect a reduction in oedema extension distance (OED) from 0.6 (SD 0.25) in the control group to 0.4 in anakinra treated subjects (alpha 0.05, power 0.80), allowing 25% drop-out.

Results: Primary outcome: Subacute perihaematomal oedema after ICH, measured as OED on MRI at day 7±1. Secondary outcomes: (1) Safety measures; (2) Serum inflammation markers and MRI measures of blood brain barrier integrity; (3) Functional recovery at 90±7 days.

Conclusions: Status: Inclusion will start summer 2021.

Trial Registration Number: EudraCT number: 2021-000324-36 Funding: Dutch Heart Foundation (grant 2019T060).

EPV0040A / #2087

Topic: AS36 ONGOING TRIALS

EFFICACY OF CEREBROLYSIN TREATMENT AS AN ADD-ON THERAPY TO MECHANICAL THROMBECTOMY – A PROSPECTIVE, OPEN LABEL, SINGLE CENTER STUDY WITH 12 MONTHS OF FOLLOW-UP

J. Staszewski¹, P. Piasecki¹, K. Gniadek-Olejniczak¹, R. Piusinska-Macoch¹, A. Dębiec¹, A. Maliborski¹, Z. Chadaide², D. Balo², G. Harston² and A. Stępień¹

¹Military Institute of Medicine, Clinic Of Neurology, Warsaw, Poland; ²Brainomix Ltd, Brainomix Ltd, Oxford, United Kingdom

Background and Aims: We hypothesized that adding Cerebrolysin in selected acute ischemic stroke (AIS) patients patients (with baseline small ischemic core, good collateral status, effective reperfusion, symptoms of cortical damage) may increase the effectiveness of mechanical thrombectomy (MT) by initiating cytoprotective effects and preventing reperfusion injury and delayed cell death. The aim of this study is to evaluate the efficacy and safety of Cerebrolysin treatment as an add-on therapy to MT in patients with AIS in the early recovery phase (90 days) and in long-term follow-up (12 months).

Methods: 50 consecutive patients will receive 30 ml of Cerebrolysin within 8h of AIS stroke onset and continue treatment once daily until day 21 and they will receive a second cycle of treatment for 21 days from Day 69 to 90. Historical control group (CG; n = 50) will be formed by retrospective clinical chart reviews of patients fulfilling the same inclusion criteria. The primary outcome measure is overall proportion of subjects experiencing a favorable functional outcome (mRS 0-2) at 7 day, 30 day and 12 months. The secondary objectives are risk of sICH, final stroke volume and penumbral salvage (measured by automatic e-STROKE software at baseline and 30 days), and changes over time in language function, hemispatial neglect, global cognitive function and depression.

Results: The study is currently recruiting patients.

Conclusions: The study is designed to test the hypothesis that a strategy combining effective endovascular revascularization with administration of neuroprotective therapies could be feasible and have additive or synergistic effects with MT and prolonged rehabilitation.

Trial Registration Number: Unique Protocol ID:0000000589; Ethics Committe Approval: 53/WIM/20 Komisja Bioetyczna przy Wpjskowym Uniwerystecie Medycznym.

EPV0182A / #2095

Topic: AS36 ONGOING TRIALS

IMPACT OF A FOCAL VIBRATION PROTOCOL APPLIED OVER THE TIBIALIS ANTERIOR MUSCLE DURING EARLY SUBACUTE POST-STROKE REHABILITATION

H. Bessaguet^1,2, B. Fernandez^1,2, D. Rimaud^1,2 and T. Lapole²

¹University Hospital Centre of Saint Etienne, Physical Medicine And Rehabilitation Department, Saint Etienne, France; ²Univ Lyon, UJM Saint-Etienne, Laboratoire Interuniversitaire De Biologie De La Motricité, Ea 7424, F-42023, Saint Etienne, France

Background and Aims: After a stroke, neuromotor impairments are responsible for activity limitations and chronic functional disorders, inducing, in turn, a significant loss of autonomy and quality of life for patients. During the early subacute phase (14 days to 3 months post-stroke onset), the ankle dorsiflexors are critically impaired, and this is widely known to contribute to difficulties in postural adjustments and ambulation. Although recommendations suggest targeting this muscle group, there is to date a lack of efficient techniques for obtaining an early onset of active and voluntary muscle contraction. Using muscular focal vibration therapy may be of interest because of its neuromotor effects in healthy subjects (Souron et al, 2017) and its recent interests observed in acute and chronic post-stroke patients (Avvantaggiato et al, 2020).

Methods: In this open-label randomized trial, the recovery of motricity (Fugl-Meyer-Assessment-Lower-Extremity scale, modified MRC-testing, modified-modified-Ashworth Scale), balance and gait skills (Timed-up-and-Go test, 2-minutes-walking test, Postural-assessment scale for stroke, posturographic parameters), will be blindly compared within 2 groups of hemiplegic patients in their early subacute phase post-stroke (for inclusion criteria, see Table 1). Both groups will follow a 4-week conventional rehabilitation program (see Figure 1) in addition to five sessions a week (30 minutes per session) of focal vibrations applied to the tibialis anterior muscle (experimental group, see Figure 2) or inactive vibrations (sham group).

Results: Ongoing Trial.

Figure 11. Figure 12. Figure 13.

Conclusions: We hypothesize that focal vibrations will provide early significant clinical motor improvements, that could be suitable for recovering better community ambulation capacities for post-stroke patients.

Trial Registration Number: NCT04737018.

EPV0183C / #2108

Topic: AS36 ONGOING TRIALS

EVALUATION OF MICROVASCULAR RAREFACTION IN VASCULAR COGNTIVE IMPAIRMENT AND HEART FAILURE: CRUCIAL-VCI

M. Van Dinther¹, P. Voorter¹, G. Thornton², T. Treibel², G. Bastarrika³, A. González⁴, E. Jones⁵, W. Backes⁶, J. Staals¹ and R. Van Oostenbrugge¹

¹Maastricht University Medical Center, Neurology, Maastricht, Netherlands; ²University College London, Cardiology, London, United Kingdom; ³Clínica Universidad de Navarra, Radiology, Pamplona, Spain; ⁴CIMA Universidad de Navarra, Cardiovascular Diseases, Pamplona, Spain; ⁵KU Leuven, Cardiovascular Sciences, Leuven, Belgium; ⁶Maastricht University Medical Center, Radiology And Nuclear Medicine, Maastricht, Netherlands

Background and Aims: Microvascular rarefaction (reduction of microvascular density) is thought to be an important mechanism in the pathophysiology of small vessel diseases such as vascular cognitive impairment (VCI) and heart failure with preserved ejection fraction (HFpEF). VCI and HFpEF often present together, and share identical cardiovascular risk factors. The international CRUCIAL consortium set out to develop novel non-invasive tools to determine microvascular health in both heart and brain using perfusion MRI, as well as easier and faster surrogate biomarkers of cerebral and/or cardiac rarefaction by investigating sublingual capillary health, vascular density of the retina, and mRNA sequencing of circulating endothelial-derived extracellular vesicles.

Methods: The clinical research program of CRUCIAL consists of several concurrent observational cohort studies in VCI patients, HFpEF patients and elderly controls. In CRUCIAL-VCI we aim to recruit 75 VCI patients and 40 controls. Main study endpoints are advanced brain and heart MRI markers for microvascular hypoperfusion and dysfunction, structural vascular brain MRI markers, cognitive function, and diastolic heart function. Regression analysis will be performed to investigate independent associations between perfusion measures in heart and brain, and measures of disease severity. Secondary study endpoints include sublingual flow-related capillary density, retinal vascular density on OCT angiography and microvesicles.

Results: Study protocol and patient information leaflet have been developed and ethical approval has been secured. Recruitment has been ongoing since December 2020. Currently we have recruited 8 VCI patients and 6 aged matched controls.

Conclusions: First results are expected in 2023. Acknowledgements: Supported by European Union’s Horizon 2020 research and innovation programme (No 848109: CRUCIAL).

Trial Registration Number: ISRCTN22301128.

EPV0183A / #2121

Topic: AS36 ONGOING TRIALS

ACT-COG: ONLINE COGNITIVE ASSESSMENT IN THE ALTEPLASE COMPARED TO TENECTEPLASE STUDY

S. Sujanthan¹, B. Menon^2,3,4 and R. Swartz^5,6

¹University of Toronto, Institute Of Medical Science, Toronto, Canada; ²Circle Neurovascular Imaging Inc., Research & Development, Calgary, Canada; ³University of Calgary, Department Of Diagnostic Imaging, Calgary, Canada; ⁴University of Calgary, Department Of Clinical Neurosciences, Calgary, Canada; ⁵Sunnybrook Health Sciences Center, Neurology, Toronto, Canada; ⁶University of Toronto, Medicine (neurology), Toronto, Canada

Background and Aims: Stroke is a leading cause of morbidity and mortality in Canada, and there is an urgent need to identify interventions that can improve cognitive outcomes after stroke. The use of remote computerized assessments has potential to improve access (especially in pandemic times), can test across multiple cognitive domains, and can be scaled to multiple centers. We are using the AcT trial (Alteplase compared to Tenecteplase; ClinicalTrials.gov trial ID: NCT03889249) to assess the feasibility of using remote computerized tasks to generate cognitive outcomes in stroke clinical trials and to compare the cognitive performances of patients who have received intravenous alteplase vs tenecteplase.

Methods: All patients with acute ischemic stroke who meet criteria for intravenous alteplase are eligible for the AcT trial. Eligible patients from the ACT trial will be invited to complete several screening questions (MoCA, computer proficiency etc.) and an online cognitive assessment using the Cambridge Brain Sciences (CBS) platform (∼30 mins) to assess cognition.

Results: As an ongoing trial, we are currently at 33% CBS completion after the first month of enrollment. We anticipate that >80% of eligible participants will complete the online testing. In addition, higher cognitive scores from the testing will be associated with higher quality of life and reduced direct and indirect costs, and participants receiving tenecteplase will demonstrate better cognitive performance than those receiving alteplase.

Conclusions: Determining the feasibility of a simple, remote cognitive assessment for use in acute stroke trials could facilitate a platform to assess the impact of various stroke interventions on short- and long-term cognition.

Trial Registration Number: Alteplase compared to Tenecteplase; ClinicalTrials.gov trial ID: NCT03889249.

EPV0183B / #2136

Topic: AS36 ONGOING TRIALS

CURRENT STATUS OF A CLUSTER-RANDOMIZED MULTIMODAL POST-STROKE CARE INTERVENTION TRIAL – THE AMBULATORY STRUCTURED POST-STROKE CARE PROGRAM (SANO)

F. Eichner¹, C. Schwarzbach², A.-L. Hofmann¹, A. Pankert², G. Hamann³, D. Sander⁴, K.G. Haeusler⁵, K. Gröschel⁶, D. Geis⁷, R. Veltkamp⁸, S. Engelter⁹, A. Meisel¹⁰, O. Busse¹¹, P. Schlattmann¹², S. Von Bandemer¹³, V. Rücker¹, M. Schutzmeier¹, P. Heuschmann¹ and A. Grau²

¹University of Würzburg, Institute For Clinical Epidemiology And Biometry, Würzburg, Germany; ²Klinikum der Stadt Ludwigshafen am Rhein, Department Of Neurology, Ludwigshafen, Germany; ³Bezirkskrankenhaus Günzburg, Clinic For Neurology And Neurological Rehabilitation, Günzburg, Germany; ⁴Benedictus Krankenhaus Tutzing, Department Of Neurology, Tutzing, Germany; ⁵University Hospital Würzburg, Department Of Neurology, Würzburg, Germany; ⁶University Hospital of the Johannes-Gutenberg University Mainz, Neurological Department, Mainz, Germany; ⁷Bayrischer Hausärzteverband, Honorary Chairman, München, Germany; ⁸Alfried Krupp Krankenhaus, Neurology, Essen, Germany; ⁹University Hospital Basel and University of Basel, Department Of Neurology And Stroke Center, Basel, Switzerland; ¹⁰Charité Universitätsmedizin Berlin, Neurology, Berlin, Germany; ¹¹Deutsche Schlaganfallgesellschaft, Deutsche Schlaganfallgesellschaft, Berlin, Germany; ¹²Universitätsklinikum Jena, Institut Für Medizinische Statistik, Informatik Und Datenwissenschaften, Jena, Germany; ¹³Ruhr Universität Bochum, Institute For Work And Technology, Gelsenkirchen, Germany

Background and Aims: The SANO trial investigates whether an evidence-based cross-sectoral post-stroke care program significantly reduces the rate of the combined endpoint including recurrent stroke, myocardial infarction and death within the first year after first-time ischemic stroke. The trial aims to establish a standardized follow-up program for stroke patients in Germany.

Methods: SANO is a parallel-arm cluster-randomized trial with a planned sample size of 2,790 patients enrolled at 30 study centers across Germany (DRKS00015322). The intervention is based on an established cross-sectoral multidisciplinary network aiming to enhance control of cardiovascular risk factors as well as detection and subsequent treatment of post-stroke complications using regular and standardized follow-up visits. The trial includes a health-economic and process evaluation.

Results: Due to the corona pandemic, recruitment of participants had to be extended for 6 months. Recruitment of 2791 patients was successfully completed in December 2020–1396 patients were randomized to the intervention group and 1395 patients to the control group (Figure 1). To date, all 30 centers are still actively involved in the trial. According to guidelines of the FDA and EMA, data collection at the final follow-up visit after 12 months has been expanded by questions reflecting the impact of the corona pandemic on the trial and the patients themselves.

Figure 14.

Conclusions: The SANO trial is running as planned within its extended time schedule. Follow-up of all patients is expected to be completed in December 2021. The main results of the SANO trial are expected in mid-2022.

Trial Registration Number: DRKS00015322.

EPV0042A / #2266

Topic: AS36 ONGOING TRIALS

DESMOPRESSIN FOR REVERSAL OF ANTIPLATELET DRUGS IN STROKE DUE TO HAEMORRHAGE (DASH): RATIONALE AND DESIGN OF A PHASE II DOUBLE BLIND RANDOMISED CONTROLLED TRIAL

N. Sprigg¹, M. Desborough², R. Al-Shahi Salman³, S. Stanworth², D. Havard¹, P. Brennan³, R. Dineen⁴, T. Coats⁵, P. Johnson¹, T. Hepburn⁶, L. Woodhouse¹, P. Bath⁷; for the DASH trial investigators

¹University of Nottingham, Stroke Trials Unit, School Of Medicine, Nottingham, United Kingdom; ²Oxford University Hospitals, Radcliffe Department Of Medicine, Oxford, United Kingdom; ³University of Edinburgh, Centre For Clinical Brain Sciences, Edinburgh, United Kingdom; ⁴Queens Medical Centre, Nottingham University Hospitals NHS Trust, Radiological Sciences Research Group, Nottingham, United Kingdom; ⁵University of Leicester, Department Of Cardiovascular Sciences, Leicester, United Kingdom; ⁶University of Nottingham, Clinical Trials Unit, Nottingham, United Kingdom; ⁷University of Nottingham, Stroke Trials Unit, Mental Health & Clinical Neurosciences, School Of Medicine, Nottingham, United Kingdom

Background and Aims: Prior antiplatelet therapy is an independent risk factor for haematoma expansion, death and poor functional outcome in spontaneous intracerebral haemorrhage. Reversal of antiplatelet effect with desmopressin was shown to be a promising therapeutic target in pilot studies.

Methods: We aim to assess the feasibility of screening, checking the eligibility, approaching, randomising, administering the intervention, and completing follow-up for patients treated with desmopressin or placebo.

Results: We aim to include 50 patients with spontaneous intracerebral haemorrhage, who were taking oral antiplatelet agents in the preceding 7 days, within 24 hours of onset. Exclusion criteria are secondary intracerebral haemorrhage and contraindications to desmopressin. Patients will be randomised (1:1) to receive intravenous desmopressin 20 μg in 50 mls Sodium Chloride 0.9% infused over 20 minutes or matching placebo. Randomisation will involve minimisation on key prognostic factors: age; sex; time since onset; systolic blood pressure; and presence of intraventricular haemorrhage. Patients, relatives, researchers and outcome assessors will be masked to treatment allocation. Feasibility outcomes include number of patients receiving allocated treatment, rate of recruitment, proportion of patients approached being randomised, adherence to treatment and follow up. Secondary outcomes include hyponatremia at 24 hour, death within 7 days, serious adverse events up to 90 days and haematoma growth at 24 hours.

Conclusions: As of 24^th June 2021, 39 participants have been recruited to this trial. This is a feasibility trial which will inform the design of a definitive trial.

Trial Registration Number: ISRCTN67038373.

EPV0042B / #2268

Topic: AS36 ONGOING TRIALS

MULTICENTER RANDOMIZED CLINICAL TRIAL OF ENDOVASCULAR TREATMENT OF ACUTE ISCHEMIC STROKE IN THE NETHERLANDS FOR LATE ARRIVALS: MR CLEAN-LATE

S. Olthuis¹, A. Pirson², W. Hinsenveld², R.-J. Goldhoorn², F. Pinckaers², A. Ceulemans², J. Staals³, I. De Ridder², W. Van Zwam⁴, M. Van Walderveen⁵, G. Lycklama A Nijeholt⁶, M. Uyttenboogaart⁷, W. Schonewille⁸, C. Majoie⁹, R. Van Oostenbrugge²; On behalf of the MR CLEAN LATE research group and the CONTRAST consortium

¹Maastricht University Medical Center+, Neurology, Maastricht, Netherlands; ²Maastricht University Medical Center and Cardiovascular Research Institute Maastricht (CARIM), Neurology, Maastricht, Netherlands; ³Maastricht University Medican Center, School for Cardiovascular Disease (CARIM), Neurology, Maastricht, Netherlands; ⁴Maastricht University Medical Center and Cardiovascular Research Institute Maastricht (CARIM), Radiology And Nuclear Medicine, Maastricht, Netherlands; ⁵Leiden University Medical Center, Radiology, Leiden, Netherlands; ⁶Haaglanden Medisch Centrum, Department Of Radiology, The Hague, Netherlands; ⁷University Medical Centre Groningen, Neurology, Groningen, Netherlands; ⁸Sint Antonius Hospital, Department Of Neurology, Nieuwegein, Netherlands; ⁹Amsterdam University Medical Centers, University of Amsterdam, Department Of Radiology And Nuclear Medicine, Amsterdam, Netherlands

Background and Aims: Endovascular therapy (EVT) within 6 hours from symptom onset is effective for acute ischemic stroke (AIS) due to a proximal large vessel occlusion (LVO) of the anterior circulation. EVT is also effective beyond the 6 hour time window in highly selected patients based on perfusion imaging. We aim to investigate whether selection based upon the presence of collateral flow in the 6-24 hour window could identify an additional group of patients for which EVT is safe and effective.

Methods: The MR CLEAN-LATE, a Dutch multicenter, prospective, randomized, open-label, blinded end-point trial, includes patients with an AIS due to a proximal LVO in the 6-24 h window and at least some collateral flow on CT-angiography. Patients with an ICA-T/M1 occlusion, NIHSS>10, infarct core<25 ml, and a penumbra≥core based on perfusion imaging will be excluded as they are eligible for EVT as standard care. The primary end-point is the modified Rankin Scale score after 90 days. Treatment effect will be estimated with ordinal logistic regression (shift analysis). Secondary outcomes include intracranial hemorrhage, mortality at 90 days, stroke severity and recanalization at 24 hours, and stroke severity and final infarct size at 5-7 days.

Results: Inclusion started in January 2018. Currently, 16 centers included 411 patients. We plan to enroll 500 patients.

Conclusions: This study will provide insights into whether late-window EVT is effective after selection based on collateral flow.

Trial Registration Number: NL58246.078.17; ISRCTN19922220.

EPV0252A / #2283

Topic: AS36 ONGOING TRIALS

EEG CONTROLLED TRIAGE IN THE AMBULANCE FOR ACUTE ISCHEMIC STROKE TRIAL (ELECTRA-STROKE)

M. Van Stigt¹, L. Van Meenen¹, A. Van De Munckhof¹, J. Van Grondelle², G. Geuzebroek², A. Siegers², M. Theunissen³, M. Smeekes³, Y. Roos¹, J. Koelman¹, W. Potters¹ and J. Coutinho¹

¹Amsterdam UMC, University of Amsterdam, Department Of Neurology, Amsterdam, Netherlands; ²Emergency Medical Services, Ambulance Amsterdam, Amsterdam, Netherlands; ³Emergency Medical Services, Ems North-holland North, Alkmaar, Netherlands

Background and Aims: Endovascular thrombectomy is the standard treatment for patients with a large vessel occlusion (LVO) stroke. Direct presentation of patients with an LVO to a comprehensive stroke center reduces onset-to-treatment time by approximately an hour and thereby improves clinical outcome. However, a reliable tool for prehospital LVO-detection is currently not available. Previous electroencephalography (EEG) studies have shown that hemispheric hypoxia quickly results in EEG-slowing. Dry electrode EEG caps allow reliable EEG-measurement in less than 5 minutes. We hypothesize that dry electrode EEG is an accurate and feasible diagnostic test for LVO in the prehospital setting.

Methods: ELECTRA-STROKE is an ongoing diagnostic pilot study that consists of four phases. In the first three phases, technical and logistical feasibility of performing dry electrode EEGs are tested in different in-hospital settings: the outpatient clinic, Neurology ward and emergency room, respectively. In the final phase, ambulance paramedics will perform dry electrode EEGs in 386 suspected stroke patients. Primary outcome is specificity of dry electrode EEG for LVO-detection. Secondary outcomes include sensitivity of EEG for LVO-detection and technical and logistical feasibility of performing EEGs in the prehospital setting. Sample size calculation is based on an expected specificity of 70% and an incidence of LVO stroke of 5%.

Results: This study started in October 2018. Phases 1 and 2 have been successfully completed. Phase 3 has been ongoing since December 2018; so far, 220/250 patients have been measured. The final phase started in August 2020: EEG has been performed in 191/386 patients thus far.

Conclusions: Ongoing trial.

Trial Registration Number: NCT03699397.

EPV0253A / #2286

Topic: AS36 ONGOING TRIALS

ENDOVASCULAR THERAPY FOR LOW NIHSS ISCHEMIC STROKES (ENDOLOW): CLINICAL TRIAL UPDATE

S. Nagel¹, P. Khatri², A. Demchuk³, R. Nogueira⁴, M. Kieser⁵, A. Vagal⁶, D. Wright⁷, S. Doppelheuer⁷, A. Hall⁸, R. Calcaterra⁸, J. Khoury⁹, H. Sucharew⁹; for the ENDOLOW Clinical Trial Investigators

¹University of Heidelberg, Neurology, Heidelberg, Germany; ²University of Cincinnati, Department Of Neurology, Cincinnati, United States of America; ³University of Calgary, Department Of Clinical Neurosciences, Calgary, Canada; ⁴Emory University, Interventional Neuroradiology, Philadelphia, United States of America; ⁵University of Heidelberg, Institute Of Medical Biometry And Informatics, Heidelberg, Germany; ⁶University of Cincinnati, Neuroradiology, Cincinnati, United States of America; ⁷EMORY UNIVERSITY SCHOOL OF MEDICINE, Emergency Medicine, Atlanta, United States of America; ⁸EMORY UNIVERSITY SCHOOL OF MEDICINE, Emergency Neurosciences, Atlanta, United States of America; ⁹Cincinnati Children’s Hospital Medical Center, Biostatistics And Epidemiology, Cincinnati, United States of America

Background and Aims: ENDOLOW is designed to determine the safety and efficacy of immediate mechanical thrombectomy (iMT) compared to immediate medical management (iMM) for patients with low National Instiute of Health Stroke Scales (NIHSS 0-5) and large vessel occlusion (LVOs).

Methods: ENDOLOW is a prospective, randomized, open-label, blinded-endpoint, multi-center, multinational clinical trial. This investigator-initiated study is funded by Cerenovus, Inc. The study is an adaptive two-stage design allowing for early stopping for efficacy or futility at the interim, or continuation to stage two after reestimating the sample size. Included patients are over 18 years of age an NIHSS of 0-5 and presence of an objective neurologic deficit, LVO (intracranial ICA, M1, M2), ASPECTS ≥ 6, and a baseline mRS ≤ 2 who present within 8 hours from last known well. The first stage will enroll up to 200 patients. Patients are randomized 1:1 to either iMT or iMM using a permuted block randomization stratified by IV tPA, time from onset to randomization, occlusion site, and age. The primary endpoint is the distribution of 90-day mRS (“shift”).

Results: ENDOLOW received formal confirmation of funding in September 2018. The trial is planned to recruit patients from the USA, Canada and Germany. 1st Enrollment was 05-SEP-2020 at Grady Memorial Hospital, Atlanta, USA. Update on trial progression will be presented at the time of the conference.

Conclusions: ENDOLOW is designed to establish the clinical value of iMT in the treatment of patients with LVOs and low NIHSS. Currently the trial is enrolling.

Trial Registration Number: NCT04167527.

EPV0254A / #2288

Topic: AS36 ONGOING TRIALS

A MULTIMODAL INDIVIDUALIZED INTERVENTION TO PREVENT FUNCTIONAL DECLINE AFTER STROKE. A RANDOMISED CONTROLLED TRIAL ON LONG-TERM FOLLOW-UP AFTER STROKE (THE LAST-LONG TRIAL)

T. Askim¹, A. Hokstad¹, E. Bergh^1,2, Ø. Døhl^1,3, H. Ellekjær^1,4, H. Ihle-Hansen⁵, B. Indredavik^1,4, S. Lydersen⁶, J. Magnussen⁷, I. Saltvedt^1,8, Y. Seljeseth⁹ and B. Thommessen²

¹NTNU-Norwegian University of Science and Technology, Department Of Neuromedicine And Movement Science, Faculty Of Medicine And Health Sciences, Trondheim, Norway; ²Akershus University Hospital, Department Of Neurology, Lørenskog, Norway; ³Trondheim kommune, Kommunedirektørens Fagstab, Trondheim, Norway; ⁴St. Olavs Hospital, Trondheim University Hospital, Department Of Stroke, Trondheim, Norway; ⁵Bærum Hospital, Stroke Unit, Department Of Medicine, Bærum, Norway; ⁶NTNU-Norwegian University of Science and Technology, Department Of Mental Health, Faculty Of Medicine And Health Sciences, Trondheim, Norway; ⁷NTNU-Norwegian University of Science and Technology, Department Of Public Health And Nursing, Trondheim, Norway; ⁸St. Olavs Hospital, Trondheim University Hospital, Department Of Geriatric Medicine, Trondheim, Norway; ⁹Møre and Romsdal Health Trust, Ålesund Hospital, Department Of Medicine, Ålesund, Norway

Background and Aims: Physical and cognitive impairments are barriers to maintain function after stroke. The main objective of the LAST-long trial is to investigate the benefit of regular follow-up by a stroke-coordinator who sets up a treatment plan targeting the individual needs for follow-up in order to prevent functional decline in the long term after stroke.

Methods: A pragmatic randomised controlled trial, with repeated measures at 6, 12 and 18 months after inclusion, is applied. Patients admitted to three Norwegian hospitals will be screened for inclusion 3-month after stroke. A total of 420 patients, age≥18, mRS<5, able to understand Norwegian and willing to sign informed consent will be included. Patients with short life expectancy or other serious diseases will be excluded. The intervention consists of regular meetings with a community-based stroke-coordinator, who will assess the patients’ risk-profile within physical health and lifestyle, mobility and ADL function, cognitive function and social function. For patients at risk within one or more of the domains, the coordinator will set up an action plan aiming to maintain or improve function. Mixed models will be used to evaluate differences between the groups for the primary (modified Rankin Scale) and secondary endpoints (cognition, motor function, extended ADL, self-perceived health, quality-of-life, frailty, vascular events, caregivers burden, health costs, etc.) across the 4 time points.

Results: By June2021, 150 patients have been included at St. Olavs Hospital (n = 75), Akershus University Hospital (n = 52) and Bærum Hospital (n = 23). Commencement of inclusion at Ålesund Hospital is in progress.

Conclusions: Follow-up will be concluded in 2024.

Trial Registration Number: ClinicalTrials.gov identifier: NCT03859063.

EPV0119A / #2303

Topic: AS36 ONGOING TRIALS

PERFORMANCE FEEDBACK ON QUALITY OF CARE IN HOSPITALS PERFORMING THROMBECTOMY FOR ISCHEMIC STROKE: A STEPPED WEDGE CLUSTER RANDOMIZED TRIAL (PERFEQTOS)

S.J. Den Hartog¹, M. Amini², N. Van Leeuwen², L.S. Kuhrij³, L.J. Stolze⁴, P.J. Nederkoorn⁴, H.F. Lingsma², A.C.G.M. Van Es⁵, I.R. Van Den Wijngaard⁶, A. Van Der Lugt⁷, D.W.J. Dippel¹, B. Roozenbeek¹; PERFEQTOS Investigators

¹Erasmus MC, University Medical Center, Neurology, Rotterdam, Netherlands; ²Erasmus MC, University Medical Center, Public Health, Rotterdam, Netherlands; ³Dutch Institute for Clinical Auditing, Dica, Leiden, Netherlands; ⁴Amsterdam University Medical Centers, location AMC, Neurology, Amsterdam, Netherlands; ⁵Leiden University Medical Center, Radiology And Nuclear Medicine, Leiden, Netherlands; ⁶Haaglanden Medical Center, Neurology, den Haag, Netherlands; ⁷Erasmus MC, University Medical Center, Radiology And Nuclear Medicine, Rotterdam, Netherlands

Background and Aims: Although provision of performance feedback to health care professionals is common practice, observational studies of its effect on quality of care have shown mixed results. We aim to assess whether performance feedback to healthcare providers in individual hospitals providing endovascular treatment (EVT) for ischemic stroke, resulting in action plans and targets based on this feedback, improves door-to-groin time and thereby quality of care.

Methods: PERFEQTOS is a stepped wedge cluster randomized trial. Thirteen hospitals in The Netherlands providing EVT for ischemic stroke, participate in this study. Performance feedback consists of 3-monthly reports with indicators on quality of care. Hospitals can compare their present performance with their own performance in the past and with other participating hospitals. The performance feedback is provided to local Quality Improvement Teams (QIT), including a neurologist, interventional neuroradiologist, and neurology resident/nurse. The QIT uses the performance feedback to define target(s) and to develop a performance improvement plan. The control group will not receive structured performance feedback and is not yet required to have a QIT. Primary outcome is door-to-groin time. Secondary outcomes include door-to-needle time, eTICI score, NIHSS after 24 hours, and mRS at 3 months.

Results: The study started in July 2020. Every 6 months three to four hospitals were randomized to cross over from the control to the intervention group. This process continues until all hospitals are crossed over to receive the feedback intervention.

Conclusions: We hypothesize that giving feedback to healthcare providers on the performance of their own hospital improves care processes and thereby quality of care.

Trial Registration Number: Dutch Trial Register; NL9090.

EPV0504A / #2314

Topic: AS36 ONGOING TRIALS

RFVIIA FOR ACUTE HEMORRHAGIC STROKE ADMINISTERED AT EARLIEST TIME (FASTEST) TRIAL

J. Broderick¹, J. Grotta², A. Naidech³, J. Elm⁴, P. Khatri¹, A. Vagal⁵, R. Aviv⁶, S. Mayer⁷, S. Janis⁸, T. Steiner⁹, H. Audebert¹⁰, N. Sprigg¹¹, C.A. Molina¹², D. Dowlatshahi¹³, K. Toyoda¹⁴, P. Khanolkar¹⁵ and J. Denlinger¹⁵

¹University of Cincinnati Academic Health Center, Neurology And Rehabilitation Medicine, Cincinnati, United States of America; ²Memorial Hermann - Texas Medical Center, Clinical Institute For Research And Innovation, Houston, United States of America; ³Northwestern University Feinberg School of Medicine, Neurology, Chicago, United States of America; ⁴Medical University of South Carolina, Public Health Sciences, Charleston, United States of America; ⁵University of Cincinnati, Neuroradiology, Cincinnati, United States of America; ⁶The Ottawa Hospital, Radiology, Ottawa, Canada; ⁷New York Medical College, Neurocritical Care And Emergency Neurology Services,Valhalla, United States of America; ⁸The National Institutes of Health, The National Institute Of Neurological Disorders And Stroke, Bethesda, United States of America; ⁹Klinikum Frankfurt Höchst, Neurology, Frankfurt am Main, Germany, ¹⁰Charité–Universitätsmedizin Berlin, Germany, Center For Stroke Research Berlin, Berlin, Germany; ¹¹Queens Medical Centre, Nottingham University Hospitals NHS Trust, Stroke Medicine, Nottingham, United Kingdom; ¹²Vall d’Hebron University Hospital, The Stroke Unit, Barcelona, Spain; ¹³The Ottawa Hospital - Civic Campus, Neurology, Ottawa, Canada; ¹⁴National Cerebral and Cardiovascular Center, Department Of Cerebrovascular Medicine, Suita, Japan; ¹⁵University of Cincinnati, Neurology, Cincinnati, United States of America

Background and Aims: The central hypothesis of FASTEST is that rFVIIa administered within 120 minutes from stroke onset with a subgroup of participants most likely to benefit will improve outcomes at 180 days (measured by mRS) and decrease bleeding (measured by 24-hour non-contrast CT), as compared to standard therapy.

Methods: FASTEST is a Phase III, randomized, double-blind controlled trial of rFVIIa (80 µg/kg (maximum 10 mg) dose) vs. placebo. Both arms will receive best standard therapy per published AHA Guidelines for ICH, including a target SBP of 140 mmHg. Participants with a volume of ICH ≥2 and <60 cc, no more than a small volume of IVH (IVH score ≤7), age ≥18 and ≤80, GCS of ≥8, and treated within 120 minutes from stroke onset will be included. To minimize time-to-treatment, the trial will use emergency research informed consent procedures (including exception from informed consent in the US) and mobile stroke units (MSUs), with a goal of ½ of participants treated within 90 minutes. FASTEST will include 100 hospitals including 16 MSUs in the NIH StrokeNet and key global institutions with large volumes of ICH patients and the ability to treat them within 120 minutes of stroke onset. Recruitment of 860 participants over 3½ years is planned. Countries participating include the US, Canada, Japan, Germany, Spain, and the UK.

Results: Enrollment is anticipated to begin summer 2021.

Conclusions: The objective of FASTEST is to establish the first treatment for acute spontaneous ICH within a time window and subgroup of patients that is most likely to benefit.

Trial Registration Number: NCT Number: 03496883 JRCT ID: jRCTs051200076 EudraCT Number: 2019-003722-25 Universal Trial Number: U1111-1201-0087.

EPV0063A / #2316

Topic: AS36 ONGOING TRIALS

DUAL THROMBOLYTIC THERAPY WITH MUTANT PRO-UROKINASE AND LOW DOSE ALTEPLASE FOR ISCHEMIC STROKE (DUMAS)

N. Van Der Ende^1,2, B. Roozenbeek^1,2, L. Aerden³, P. Kraayeveld⁴, I. Van Den Wijngaard⁵, G. Lycklama A Nijeholt⁶, H. Den Hertog⁷, H. Flach⁸, L. Smagge¹, H. Lingsma⁹, A. Van Der Lugt¹, D. Dippel²; DUMAS investigators

¹Erasmus MC University Medical Center, Radiology & Nuclear Medicine, Rotterdam, Netherlands; ²Erasmus MC University Medical Center, Neurology, Rotterdam, Netherlands; ³Reinier de Graaf, Neurology, Delft, Netherlands; ⁴Reinier de Graaf, Radiology & Nuclear Medicine, Delft, Netherlands; ⁵Haaglanden MC, Neurology, The Hague, Netherlands; ⁶Haaglanden MC, Radiology & Nuclear Medicine, The Hague, Netherlands; ⁷Isala Hospital, Neurology, Zwolle, Netherlands; ⁸Isala Klinieken, Radiology & Nuclear Medicine, Zwolle, Netherlands, ⁹Erasmus MC University Medical Center, Public Health, Rotterdam, Netherlands

Background and Aims: The effectiveness of alteplase for ischemic stroke treatment is limited and the occurrence of intracranial and extracranial hemorrhage is a major limitation. Mutant pro-urokinase (m-pro-urokinase) does not deplete fibrinogen and lyses fibrin only after induction with alteplase. Our aim is to test the safety and efficacy of dual thrombolytic treatment consisting of a bolus alteplase followed by m-pro-urokinase against usual treatment with alteplase in patients presenting with ischemic stroke.

Methods: DUMAS is a multicenter, phase II, randomized clinical trial with open-label treatment, adaptive design for dose optimization, and blinded outcome assessment. Patients with ischemic stroke, who meet the criteria for treatment with intravenous (IV) alteplase can be included. Patients eligible for endovascular thrombectomy are excluded. Patients will be randomly assigned (1:1) to receive a bolus of IV alteplase (5 mg) followed by continuous IV infusion of m-pro-urokinase (40 mg/hr during 60 minutes) or usual care with alteplase (0.9 mg/kg). We aim to include 200 patients with a discharge diagnosis of ischemic stroke. The primary outcome is any post-intervention intracranial hemorrhage (ICH) on MRI according to the Heidelberg Bleeding Classification. Secondary outcomes include symptomatic ICH, NIHSS scores at 24 hours and 5-7 days, and mRS score at 30 days.

Results: First patient was included August 10^th, 2019. Currently, 106 patients have been included as of July 1, 2021.

Conclusions: The trial is well underway. It will test the hypothesis that dual thrombolytic therapy with a bolus alteplase and m-pro-urokinase reduces the occurrence of ICH in patients with ischemic stroke compared to patients treated with alteplase alone.

Trial Registration Number: NL7409 (www.trialregister.nl) and NCT04256473 (ClinicalTrials.gov).

EPV0536A / #2347

Topic: AS36 ONGOING TRIALS

RATES, RISKS AND ROUTES TO REDUCE VASCULAR DEMENTIA (R4VAD)

E. Backhouse¹; The R4VaD Collaborators

¹Edinburgh Imaging and the UK Dementia Research Institute at the University of Edinburgh, UK, Centre For Clinical Brain Sciences, Edinburgh, United Kingdom

Background and Aims: R4VAD is a multi-site longitudinal, inclusive observational study of patients presenting with stroke to UK stroke centres aiming to determine rates of, and risk factors for, cognitive and related impairments after stroke, assess mechanisms and improve prediction models.

Methods: R4VaD is recruiting patients within 6 weeks of stroke and collecting clinical, socioeconomic, lifestyle, cognitive, mood and informant data using clinical trial methods. Detailed assessments are obtained at 6+/-2 weeks post baseline assessment, with annual follow-up by phone and post to at least 2 years and data linkage for 10 years. Diagnostic neuroimaging is assessed in all, and inflammatory blood markers and genetic analysis in as many patients as possible. Recruitment opened in September 2018, paused briefly in March 2020 and reopened in April 2020 with a COVID-19 substudy.

Results: We have recruited 2143 participants to date (initial a target 2000) in 53 Centres across the UK (mean age = 68.5 years, SD = 13.5; 39.8% female). So far, 85% of participants have ischaemic stroke; 8% ICH; 6% TIA; mean NIHSS = 2.9 (SD = 3.4); 6% lack capacity; 31% have an informant. Prevalent vascular risk factors include: hypertension (63%); current/ex-smoker (58%); hyperlipidaemia (45%); previous stroke/TIA (28%). At baseline, mean scores were: MOCA = 23.0/30, SD = 4.2; anxiety (GAD-7) = 3.9/21, SD = 4.8 (≥5 suggests anxiety) and depression (Zung) = 46.0/80, SD = 13.5 (≥50 suggests depression).

Conclusions: R4VAD will provide reliable data on cognitive and neuropsychiatric consequences long-term after stroke; improve understanding of clinical, demographic, laboratory, neuroimaging and social predictors of post-stroke cognitive impairment and dementia as well as provide objective data on the impacts of COVID-19 on stroke.

Trial Registration Number: ISRCTN18274006.

EPV0026A / #2350

Topic: AS36 ONGOING TRIALS

OPTIMAS: A RANDOMISED CONTROLLED TRIAL TO ESTABLISH THE OPTIMAL TIMING OF ANTICOAGULATION AFTER ACUTE ISCHAEMIC STROKE

L. Arram¹, J.G. Best², R. Fenner³, M. Chau³, M. Balogun³, E. Caverly³, N. Ahmed³, E. Bordea³ and D. Werring⁴

¹Stroke Research Centre, Institute Of Neurology, London, United Kingdom; ²UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Stroke Research Center, Department Of Brain Repair And Rehabilitation, London, United Kingdom; ³CCTU, Cctu, London, United Kingdom, ⁴UCL Queen Square Institute of Neurology, Stroke Research Centre, London, United Kingdom

Background and Aims: Atrial fibrillation (AF) causes at least one-fifth of ischaemic strokes, with a high risk of early recurrence. Although oral anticoagulation is highly effective for reducing the long-term risk of recurrent ischaemic stroke in patients with AF, its benefit in the acute phase after stroke is unclear. OPTIMAS is a large randomised controlled trial aiming to establish the safety and efficacy of early anticoagulation with a direct oral anticoagulant (DOAC) in this large patient group.

Methods: OPTIMAS will enrol 3478 participants with acute ischaemic stroke and AF over 3 years from >100 stroke services in the United Kingdom. Participants will be randomised 1:1 to early (within 4 days) or standard (between day 7 and 14 after stroke) initiation of anticoagulation with any licensed DOAC. Follow-up is at 90 days, blinded to treatment allocation. The primary outcome is the combined incidence of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, and systemic arterial embolism. Secondary outcomes include bleeding, functional, cognitive, quality-of-life, and health-economic measures.

Results: OPTIMAS opened in June 2019 and is recruiting from 80 UK sites. As of the 5th July 2021, 1058 participants have been randomised. Recruitment and site-set up were reduced during the early part of the pandemic. Current recruitment has surpassed pre-pandemic levels and 9 sites are currently in set-up.

Conclusions: OPTIMAS will determine the efficacy and safety of a strategy with the potential to prevent early recurrent ischaemic strokes, reduce hospital stays, and change acute stroke care pathways for patients with AF. The trial is actively recruiting and expressions of interest are welcomed.

Trial Registration Number: NCT03759938 ISRCTN17896007.

EPV0338B / #2355

Topic: AS36 ONGOING TRIALS

THE NIH STROKENET TRIALS IMPLEMENTATION

J. Broderick¹, P. Khatri¹, J. Elm², W. Zhao², C. Dillon², S. Janis³ and R. Conwit³

¹University of Cincinnati Academic Health Center, Neurology And Rehabilitation Medicine, Cincinnati, United States of America; ²Medical University of South Carolina, Public Health Sciences, Charleston, United States of America; ³The National Institutes of Health, The National Institute Of Neurological Disorders And Stroke, Bethesda, United States of America

Background and Aims: The NIH StrokeNet infrastructure, established in 2013, consists of the National Coordinating Center at the University of Cincinnati that provides coordination of network activities; the National Data Management Center at the Medical University of South Carolina that coordinates centralized and standardized data collection, monitoring, and statistical support; 27 Regional Coordinating Centers that manage 475 network sites; and the National Institute of Neurological Disorders and Stroke that provides administrative and scientific input. StrokeNet uses a central Institutional Review Board, and has a Training Core for educating and mentoring StrokeNet fellows.

Methods: In the earlier years, StrokeNet’s evolving trial submission and review process had been a high priority of network development. Attention is now focused on implementing trials that have been developed and funded through the review process.

Results: There have been 119 concept proposals (Acute-46, Prevention-45, Recovery-28) submitted, 42 have been approved for scientific review with 48 feasibility assessments done by site survey prior to submission. The first StrokeNet trial, DEFUSE 3, recruited ahead of projection and was halted early for overwhelming efficacy. TeleRehabilitation met recruitment projections and finished on schedule. ARCADIA, MOST, Sleep SMART, TRANSPORT2, I-ACQUIRE, ARCADIA-CSI, SATURN, and ASPIRE trials are currently enrolling. FASTEST will start enrolling by the end of July 2021. COVID-19 required shutting down the network for 55 days in 2020. Trial protocol modifications and the addition of remote consenting and eConsent were instituted to resume enrollments safely.

Conclusions: NIH StrokeNet has demonstrated the ability to implement innovative and impactful trials and respond to unprecedented events such as COVID-19.

Trial Registration Number: Not applicable.

EPV0338C / #2361

Topic: AS36 ONGOING TRIALS

A TRIAL TO EVALUATE SAFETY AND BIOLOGICAL EFFECT OF APTOLL: APRIL PHASE IB SAFETY RESULTS

M. Hernández-Jiménez¹, J. Vivancos², M. Hernández³, P. Cardona⁴, F. Moniche⁵, J. Montaner⁶, M. Dalsgaard⁷, J. Casariego⁸, T. Jovin⁹, C.A. Molina¹⁰ and M. Ribo¹¹

¹AptaTargets S.L., Dpto. Científico, Madrid, Spain; ²Hospital Universitario de La Princesa, Neurology, Madrid, Spain; ³Hospital Germans Trias i Pujol, Neurology, Barcelona, Spain; ⁴Hospital Universitari de Bellvitge, Barcelona, Spain., Neurology, Barcelona, Spain; ⁵Hospital Universitario Virgen del Rocío, Neurology, Sevilla, Spain; ⁶Vall d'Hebron Research Institute (VHIR), Neurovascular Research Laboratory, Barcelona, Spain; ⁷Lundbeck, Experimental Medicine & Clinical Development, Copenhagen, Denmark; ⁸Stemline Therapeutics, Inc, Clinical Development & Medical Affairs, Madrid, Spain; ⁹University of Pittsburgh Medical Center, Department Of Neurology, Pittsburgh, United States of America; ¹⁰Vall d’Hebron Hospital, The Stroke Unit, Barcelona, Spain; ¹¹Vall d'Hebrón University Hospital, Stroke Unit, Barcelona, Spain

Background and Aims: In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) plus neuroprotective drugs, demonstrates that there is an urgent medical need of developing a new acute ischemic stroke (AIS) medicinal product targeting therapeutic pathways other than reperfusion. ApTOLL, an anti-inflammatory drug with proven neuroprotectant effects in preclinical models, is a promising first-in-class aptamer with potential to address such unmet need.

Methods: APRIL trial is being performed. This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in AIS patients. The study population are men and non-pregnant women with confirmed AIS with a <6 h window from symptoms onset to ApTOLL/placebo administration. In Phase Ib, 32 patients have been allocated in four dose ascending levels to select the best two doses to be administered in Phase IIa, based on safety criteria.

Results: Phase Ib has concluded. A total of 90 adverse events (AEs) and 13 serious AEs have been reported, none of them considered related to ApTOLL administration. Among the AEs/SAEs detected, most of them were linked to nervous system disorders (approximately 50%) and infections, as expected considering the characteristics of AIS patients. Non increase in AEs/SAEs were detected among groups of patients or dose levels. Additionally, the pharmacokinetic analysis shows that the behavior of ApTOLL in AIS patients is similar to that observed in healthy volunteers.

Conclusions: APRIL Phase Ib study reveals that the administration of ApTOLL in four dose levels in AIS patients is safe. APRIL Phase IIa is ongoing.

Trial Registration Number: NCT04734548.

EPV0434A / #2364

Topic: AS36 ONGOING TRIALS

COMBINATION ANTITHROMBOTIC TREATMENT FOR PREVENTION OF RECURRENT ISCHEMIC STROKE IN INTRACRANIAL ATHEROSCLEROTIC DISEASE (CATIS-ICAD)

D. De Sa Boasquevisque¹, M. Sharma¹, M. Hill², J. Eikelboom¹, K. Ng¹, W. Oczkowski¹, R. Hart¹, K. Perera¹ and O.B.O. Catis-Icad Investigators1

¹Population Health Research Institute, McMaster University, Department Of Medicine, Hamilton, Canada; ²University of Calgary, Clinical Neurosciences, Calgary, Canada

Background and Aims: ICAD is a major cause of ischemic stroke. The COMPASS trial (n = 27,395) demonstrated an overwhelming efficacy in reducing ischemic strokes in patients with systemic atherosclerosis, by using the combination of rivaroxaban 2.5 mg twice daily plus aspirin (ASA) in comparison to ASA alone. A subgroup analysis of patients with remote stroke (n = 1032) revealed that the combination reduced risk of ischemic stroke by 67% without increasing the risk of intracranial hemorrhage. The CATIS-ICAD trial will assess stroke patients and aims to establish feasibility, safety and preliminary efficacy of low-dose rivaroxaban plus ASA in preventing recurrent strokes secondary to ICAD.

Methods: CATIS-ICAD is a pilot trial with PROBE design that will recruit 100 patients with recent (7-100 days from index event) ischemic stroke/high-risk TIA secondary to ICAD. Follow-up is for an average of 12 months. Feasibility of recruitment and safety are primary outcomes and overt and covert recurrent stroke rates are secondary outcomes.

Results: Fourty-eight participants have been randomized to date. Mean age 67.5 ±12.5; 76% male. White (83%) and Asian (10%) were the most frequent race. 73% of patients presented with stroke as a qualifying event and median NIHSS of 1 (0-1.0) at the time of randomization. Half of the patients had severe stenosis, and 1/3 had mild stenosis. The culprit artery was either intracranial internal carotid artery or middle cerebral artery in 2/3 of patients.

Figure 15.

Conclusions: CATIS-ICAD will provide preliminary data on safety of low-dose rivaroxaban plus ASA in reducing ICAD related ischemic events that will pave way to a larger phase III trial.

Trial Registration Number: NCT04142125.

EPV0476A / #2368

Topic: AS36 ONGOING TRIALS

EDOXABAN FOR STROKE PREVENTION IN INTRACRANIAL HEMORRHAGE SURVIVORS WITH ATRIAL FIBRILLATION: DESIGN OF THE ONGOING ENRICH-AF GLOBAL RANDOMIZED TRIAL

L. Catanese¹, R. Al-Shahi Salman², D. Dowlatshahi³, R. Lemmens⁴, P. Kafle⁵, M. Ahmed⁶, H. Aref⁷, A.M. De Arce Borda⁸, M.D.M. Castellanos Rodrigo⁹, A. Khaw¹⁰, S. Jalini¹¹, N. Borah¹², K. Adie¹³, C.A. Molina¹⁴, K. Muir¹⁵, R. Huber¹⁶, A. Moussady¹⁷, I. Casado Naranjo¹⁸, A. Dahal¹⁹, W. Tarhuni²⁰, E. Tageldin²¹, T. Belal²², C. Dafe²³, K. Reeh²⁴, A. Taylor²⁴, A. Benz²⁴, A. Katsanos¹, R. Hart²⁵, S. Connolly²⁵, A. Shoamanesh¹; on behalf of the ENRICH-AF Steering Committee

¹McMaster University, Population Health Research Institute, Hamilton, Canada; ²University of Edinburgh, Centre For Clinical Brain Sciences, Edinburgh, United Kingdom; ³The Ottawa Hospital - Civic Campus, Neurology, Ottawa, Canada; ⁴UZ Leuven, Neurology, Leuven, Belgium; ⁵Nobel Medical College, Medicine, Biratnagar, Nepal; ⁶Fayoum University, Neurology, Faiyum, Egypt; ⁷Ain Shams University, Neurology, Cairo, Egypt; ⁸Donostia University, Neurology, Donostia, Spain; ⁹University of A Coruna, Neurology, A Coruna, Spain; ¹⁰Western University, Clinical Neuroscience, London, Canada; ¹¹Queen's University, Medicine, Kingston, Canada; ¹²GNRC Hospital, Neurology, Guwahati, India; ¹³Royal Cornwall Hospital, Phoenix Ward, Truro, United Kingdom; ¹⁴Hospital Universitaru Vall d’Hebrón, Barcelona, Spain., Neurology, Barcelona, Spain; ¹⁵University of Glasgow, Institute Of Neuroscience & Psychology, Glasgow, United Kingdom; ¹⁶Klinikum Friedrichshafen, Neurology, Friedrichshafen, Germany; ¹⁷Montreal Neurological Institute - McGill University, Neurology, Montreal, Canada; ¹⁸Complejo Hospitalario Universitario de Cáceres, Neurology, Cáceres, Spain; ¹⁹B P Koirala Institute of Health Sciences, Neurosurgery, Dharan, Nepal; ²⁰University of Saskatchewan, Medicine, Saskatoon, Canada; ²¹Tanta University, Neurology, Tanta, Egypt; ²²Mansoura University, Neurology / Faculty Of Medicine, Mansoura, Egypt; ²³Rhema Research Institute, Neurology, Owen Sound, Canada; ²⁴Population Health Research Institute, Stroke And Cognition, Hamilton, Canada; ²⁵Population Health Research Institute, McMaster University, Department Of Medicine, Hamilton, Canada

Background and Aims: Available data suggest that non-vitamin K antagonist oral anticoagulants are a promising treatment option for intracranial hemorrhage (ICrH) survivors with atrial fibrillation (AF). We hypothesize that treatment with edoxaban will reduce the risk of stroke in ICrH survivors with high-risk AF compared with non-anticoagulant medical therapy.

Methods: International, investigator-initiated, randomised, open-label, blinded end-point trial comparing edoxaban 60/30 mg once daily with non-anticoagulant medical therapy (either no antithrombotic or antiplatelet monotherapy) in patients with AF and prior ICrH.

Results: The planned sample size of 1200 participants will be recruited from approximately 300 sites in Africa, Asia, Europe, and North and South America between 2019 and 2023 and followed for a mean of about 2 years until at least 123 primary efficacy outcome events have occurred. The study will have 80% power to detect a 40% reduction in the primary outcome of stroke by edoxaban vs. non-anticoagulant medical therapy. Participants are eligible if they are aged ≥45 years with high-risk AF (CHA₂DS₂-VASc≥2) and previous ICrH (intraventricular, intraparenchymal, convexity subarachnoid or subdural hemorrhages occurring on or off antithrombotic therapy). Patients within 14 days of their ICrH, with secondary causes of ICrH, specific contraindications to edoxaban, absolute indication for non-study assigned antithrombotic treatment, and/or severe renal impairment are not eligible.

Conclusions: ENRICH-AF is the largest planned randomized trial of oral anticoagulation for patients with AF after ICrH. The trial is currently active at 125 sites in 13 countries and it has enrolled 129 participants as of July 5th, 2021.

Trial Registration Number: NCT03950076.