CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
GENERAL OR LOCAL ANESTHESIA IN INTRA ARTERIAL THERAPY (“GOLIATH”): A RANDOMIZED TRIAL
C.Z. Simonsen1, A.J. Yoo2, L.H. Sørensen3, N. Juul4, S.P. Johnsen5, G. Andersen1 and M. Rasmussen4
1Aarhus University Hospital, Neurology, Aarhus, Denmark
2Texas Stroke Institute, Radiology, Dallas-Fort Worth, USA
3Aarhus University Hospital, Neuroradiology, Aarhus, Denmark
4Aarhus University Hospital, Neuroanesthesiology, Aarhus, Denmark
5Aarhus University Hospital, Clinical Epidemiology, Aarhus, Denmark
Background and Aims: Endovascular therapy (EVT) is now evidence based. There is uncertainty regarding the effect of the anesthetic approach. Observational studies suggest that general anesthesia (GA) during EVT is associated with worse outcomes compared to conscious sedation (CS).
We aimed to examine whether GA caused greater infarct growth and worse outcomes during EVT by randomizing patients to either GA or CS. Patients were MRI scanned before and 48–72 hours after EVT. Patients were contacted by an independent observer 90 days post-stroke to asses the modified Rankin scale (mRS).
Method:
Inclusion criteria
- anterior circulation large vessel stroke
- 6 hour time window
- mRS 0–2
- presenting infarct volume <70 cc
- Not intubated at arrival/Glasgow Coma Scale>8
Results: A total of 128 patients were included in the study. Sixty-two were randomized to CS; four were converted to GA. (Conversion rate 6%). Analysis was done by “intention to treat”.
The two groups were balanced (Table 1). The GA group took approximately 9 minutes longer to prepare for EVT. Significantly more patients in the GA group experienced a drop in blood pressure. Results concerning infarct growth and 90 day mRS will be presented at the conference.
Table 1: For categorical values, a Chi-square test was performed. Age and time to groin were normally distributed and mean and standard deviation are presented. For the other continuous variables, a Mann-Whitney test was done. Median and interquartile ranges are shown.
Conclusion: The results from this study may guide future decisions regarding the optimal anesthetic regime for EVT.
LB01-003
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
THE EFFECT OF ALTEPLASE ON HEALTH CARE UTILISATION AND QUALITY OF LIFE IN SWEDEN, NORWAY AND SCOTLAND: RESULTS FROM THE 3RD INTERNATIONAL STROKE TRIAL (IST-3)
E. Berge1, J. Smith2, P. Sandercock3, W. Whiteley3, E. Lundström4, K.B. Slot1, L. Kleven1, A.S. Rudberg4 and J. Forbes5
1Oslo University Hospital, Department of Internal Medicine, Oslo, Norway
2University of Oxford, Nuffield Department of Population Health, Oxford, United Kingdom
3UNIVERSITY OF EDINBURGH, Centre for Clinical Brain Sciences, Edinburgh, United Kingdom
4Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden
5University of Limerick, Graduate Entry Medical School, Limerick, Ireland
Background and Aims: Prompt treatment of acute ischaemic stroke with alteplase improves functional outcome. Previous studies of the cost effectiveness of alteplase have used simulated state transition models that have not been validated using within-trial estimates of comparative and cost effectiveness. We aimed to estimate health care utilisation, quality adjusted survival and cost-effectiveness of alteplase in a subset of individual participants in the third International Stroke trial.
Method: IST-3 was an international, multi-centre, randomised open-label trial in patients presenting with acute ischaemic stroke within 6 hours of onset of alteplase + best medical management versus best medical management with blinded assessment of outcome. We obtained linked health care utilisation data on 628 individual participants from Scotland, Norway and Sweden from National electronic health records. Costs were estimated for alteplase therapy and the index and subsequent hospital episodes up to 6 and 18 months post-randomisation. Survival times were adjusted using EQ-5D-3L at baseline, 6 and 18 months to derive quality-adjusted survival times.
Results: Treatment with alteplase reduced health care resource utilization across the 18 month follow-up. The result was driven by a non-trivial reductions in acute hospital inpatient and subsequent day case episodes, which was consistent over the 6 and 18 month follow-up.
Conclusion: We will present the effect of alteplase on quality-adjusted survival and health resource usage in this trial population of older subjects and discuss the generalisability and implications of the results from this unique three-country health economic study.
LB01-004
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
THE ANSTROKE TRIAL
Background and Aims: Retrospective studies have shown worse neurological outcome after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) managed with general anesthesia (GA) during the procedure, compared to patients managed with conscious sedation (CS). However, all these studies suffer from pronounced selection bias.
The AnStroke trial is a single-center, randomized trial, with the aim to compare neurological outcome after EVT in patients randomized to GA or CS.
Three-hundred-twenty-one patients were screened for eligibility from Nov 2013 to July 2016 and 106 were subsequently randomized to GA or CS. Ninety patients, 45 in each group, were finally analyzed in relation to mRS 3 months (primary end-point), NIHSS at 24 hours, three days and at discharge or day 4–7. A MRI was performed day three for infarct volume estimation.
Demographics, administration of intravenous thrombolysis, occlusion site, ASPECT score, collateral circulation, blood glucose, blood gas samples and relevant time intervals were recorded. Invasive blood pressure was noted every 5 minutes and anesthesiologists were involved in all procedures. Anesthesiological and interventional complications were recorded.
The choice of embolectomy technique was at the discretion of the neurointerventionist in charge. The angiographic result was defined according to the modified Thrombolysis In Cerebral Ischemia (mTICI) score.
Results: The neurological outcomes, measured as mRS 3 months (primary outcome), NIHSS and infarction volume, for patients randomized to GA or CS before EVT, will be presented at ESOC May 18 2017.
Conclusion: Please see Results section
LB01-005
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
TIME DELAYS AND ENDOVASCULAR TREATMENT EFFECT: A PRESPECIFIED PATIENT-LEVEL POOLED ANALYSIS OF ALL AVAILABLE TRIALS. The VISTA-Endovascular Collaborators
Background and Aims: Time from onset to treatment has been recognized as an important modifier of the effect of endovascular treatment. However, effect estimates have not been precise and the role of other prognostic factors and imaging parameters in conjunction with time has not been addressed sufficiently in previous trial reports and pooled analyses. We pre-specified an individual pooled data (IPD) analysis to test how time from onset modifies the treatment effect of endovascular therapy.
Method: An individual pooled data (IPD) analysis of all eligible trials in the VISTA-Endovascular repository is underway (Int J Stroke 2015;10:136-44). We tested whether predefined time parameters, including time to groin and time to reperfusion modify treatment effect of EVT (with IV rtPA) versus IV rtPA alone. We considered trials with ≥85% modern devices and ≥20 patients. The primary outcome was the full 90-day modified Rankin Scale at three months (mRS 5–6 combined). We will assess how clinical and imaging parameters affect the relation between time and treatment effect. Sensitivity analyses will expand cohorts to include IV rtPA-ineligible patients, and trials with <85% modern devices and/or <20 patients.
Results: The primary cohort consists of 1683 patients from ESCAPE, EXTEND IA, MR CLEAN, PISTE, REVASCAT, SWIFT PRIME, THERAPY, and THRACE. Preliminary results indicate a strong interaction between treatment effect and time from onset to groin (p = 0.02) as well as time from onset to reperfusion (p = 0.03).
Conclusion: The effect of endovascular treatment is confirmed to be highly time dependent. Full results will be provided at the presentation.
LB01-006
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
Endovascular revascularization with contact aspiration versus stent retriever in acute Ischemic stroke with large vessel occlusion. The ASTER TRIAL. A Randomized Clinical Trial
B. Lapergue1, R. Blanc2, B. Gory3, J. Labreuche4, A. Duhamel4, G. Marnat5, S. Saleme6, V. Costalat7, S. Bracard8, H. Desal9, M. Mazighi2, A. Consoli10 and M. Piotin2
1Foch Hospital University Of Versaille Saint Quentin En Yvelines, Stroke Center, Suresnes, France
2Rothschild Foundation, Department of Interventional Neuroradiology, paris, France
3Hospices Civils de Lyon, Department of Interventional Neuroradiology, Bron, France
4Univ. Lille- CHU Lille- EA 2694 - Santé publique: Epidémiologie et Qualité des Soins, Department of Biostatistics, Lille, France
5CHU Pellegrin, Department of Interventional Neuroradiology, Bordeaux, France
6CHU Dupuytren, Department of Interventional Neuroradiology, Limoges, France
7CHU Hôpital Gui de Chaulac, Department of Interventional Neuroradiology, Montpellier, France
8Hôpital Neurologique, Department of Interventional Neuroradiology, Nancy, France
9Hôpital Guillaume et René Laennec, Department of Interventional Neuroradiology, Nantes, France
10Foch Hospital University Of Versaille Saint Quentin En Yvelines, Department of Interventional Neuroradiology, Suresnes, France
Background and Aims: Benefits of endovascular revascularization with contact aspiration technique versus stent retriever in acute ischemic stroke remains unknown due to lack of evidence from randomized trials. We sought to assess whether thrombectomy with contact aspiration is superior to stent retriever for successful reperfusion among acute stroke patients with large vessel occlusion.
Method: ASTER is a prospective, randomized, controlled, open-label, blinded end-point, clinical trial. Patients with acute ischemic stroke and major occlusion were randomly assigned to frontline contact aspiration group (n = 192) or frontline stent retriever (n = 189) immediately prior mechanical thrombectomy. Primary outcome was the percentage of patients with successful recanalization at the end of angiography.
Results: Between October 2015 and October 2016, a total of 381 patients underwent randomization in 8 comprehensive stroke centers and all were included in intention to treat analysis. The primary efficacy outcome was achieved similarly in aspiration and stent retriever groups (85.4% versus 83.1%; P = 0.53). Similar result was found in sensitivity analysis using mTICI score assessed after frontline strategy alone, or when successful reperfusion was defined as mTICI score 3. Of the clinical efficacy outcomes (early neurological improvement, modified Rankin score at three months), and safety outcomes, we found no significant differences between the two arms.
Conclusion: Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, frontline thrombectomy with contact aspiration vs stent retriever did not result in greater successful reperfusion rate at the end of the procedure. The study findings do not support major differences between contact aspiration and stent retriever frontline reperfusion techniques.
NCT02523261.
LB01-007
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
MODIFIERS OF ENDOVASCULAR TREATMENT EFFECT: A PRESPECIFIED PATIENT-LEVEL POOLED ANALYSIS OF ALL AVAILABLE TRIALS. The VISTA-Endovascular Collaborators
P. Khatri1
1University of Cincinnati, Neurology, Cincinnati, USA
Background and Aims: The stroke field has progressed, from asking “whether” there is benefit, to “who” will benefit from endovascular therapy (EVT). A post-hoc pooling of five trials with predominantly stent retrievers demonstrated benefit for most patients with anterior circulation occlusions, irrespective of baseline characteristics. We reassess these findings in a broader set of trials using our prespecified analysis plan that includes different definitions of key variables and a novel, sequential approach to incorporating future trials.
Method: An individual pooled data (IPD) analysis of all eligible trials in the VISTA-Endovascular registry is underway (Int J Stroke, 2015). We have tested age (continuous), NIHSS (continuous), and ASPECTS (0–4, 5–7, or 8–10) as treatment effect modifiers of EVT (with IV rtPA) vs. IV rtPA alone on the full, 90-day modified Rankin Scale (mRS; 5–6 combined). We will also test intracranial occlusion location and presence of ipsilateral extracranial carotid occlusion. The primary analysis consists of only trials with ≥85% modern devices and ≥20 patients. Sensitivity analyses will expand the cohorts.
Results: As of 11/MAR/2017, all systematic search-identified, randomized trials testing EVT that were completed worldwide had submitted data to the VISTA-Endovascular trial data repository. The primary cohort consists of 1683 patients from ESCAPE, EXTEND IA, MR CLEAN, PISTE, REVASCAT, SWIFT PRIME, THERAPY, and THRACE trials. Preliminary results of the primary cohort verify EVT treatment effect (adjusted OR 1.94; 95% CI 1.55–2.4) and no interaction by age, NIHSS, and ASPECTS in unadjusted testing.
Conclusion: Endovascular treatment effect remains robust. Full results will be provided at the presentation.
LB01-008
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
THROMBOLYSIS OR ANTICOAGULATION FOR CEREBRAL VENOUS THROMBOSIS (TO-ACT): A RANDOMISED CONTROLLED TRIAL
J. Coutinho1, J. Ferro2, S. Zuurbier1, R. de Haan3, J. Reekers4, E. Houdart5, I. Crassard6, P. Canhao2, M.G. Bousser6 and J. Stam1
1Academic Medical Center University of Amsterdam, Neurology, Amsterdam, The Netherlands
2Hospital Santa Maria, Neurology, Lisbon, Portugal
3Academic Medical Center University of Amsterdam, Clinical Epidemiology, Amsterdam, The Netherlands
4Academic Medical Center University of Amsterdam, Radiology, Amsterdam, The Netherlands
5Hopital Lariboisiere, Radiology, Paris, France
6Hopital Lariboisiere, Neurology, Paris, France
Background and Aims: Endovascular treatment (ET) may be beneficial for a subgroup of patients with cerebral venous thrombosis (CVT) who have a high risk of poor outcome, despite anticoagulant treatment. Published experience on ET in patients with CVT is promising, but consists only of non-randomised studies.
Objective: To investigate whether ET improves clinical outcome of patients with CVT.
Method: We performed a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) trial. Eligible were adults with radiologically proven CVT and one or more risk factors associated with poor outcome: mental status disorder, coma, intracerebral hemorrhage, or thrombosis of the deep venous system. We used web-based randomisation to allocate patients in a 1:1 ratio to ET plus anticoagulation in therapeutic dose (intervention) or anticoagulation alone (control). ET consisted of local intra-sinus application of rt-PA or urokinase, mechanical thrombectomy, or a combination of both. The primary endpoint was the modified Rankin Scale (mRS) score at 12 months. Secondary endpoints included the mRS at 6 months, mortality, and recanalisation at 6 months. Major bleeding complications were the principal safety endpoint. The trial was designed to detect a 20% reduction in poor outcome (mRS 2–6), from 40% to 20%.
Results: Between September 2011 and October 2016, 67 patients were randomised (33 intervention and 34 control) in 14 hospitals in 6 countries. After the first interim analysis in November 2016, the trial was terminated because of futility.
Conclusion: Final results of the TO-ACT trial will be presented at the ESO conference.
Funding: Dutch Heart Foundation.
Trial registration: ClinicalTrials.gov, number NCT01204333.
LB01-009
CLINICAL TRIAL RESULTS – ACUTE MANAGEMENT – THROMBOLYSIS OR THROMBECTOMY
Real-World Applicability of Endovascular Therapy in ICA and/or MCA-M1 Occlusions Treated in the 6–24-hour Window: Subgroup Analysis of the Prospective Trevo Registry
R. Nogueira1, D. Liebeskind2, R. Budzik3, R. Gupta4, A. Krajina5, J. English6, B. Baxter7, B. M. Bartolini8, A. Malek9, A. Sarraj10, A. P. Narata11, M. Taqi12, T. Miller13, T. Grobelny14, L. Estrade15, T. Jovin16 and E. Veznedaroglu17
1Grady Memorial Hospital- Emory University School of Medicine, Neurology, Atlanta, USA
2UCLA, Neurology, Los Angeles, USA
3Riverside Medical Center, Radiology, Columbus, USA
4WellStar Health System, Neurology, Marietta, USA
5Charles University Hospital, Radiology, Hradec Králové, Czech Republic
6California Pacific Medical Center, Neurology, San Francisco, USA
7Erlanger Medical Center, Radiology, Chattanooga, USA
8Hôpital La Pitié-Salpêtrière, Radiology, Paris, France
9St. Mary's Medical Center, Neurology, West Palm Beach, USA
10University of Texas - Houston, Neurology, Houston, USA
11Hopital Bretonneau, Neurosurgery, Tours, France
12Los Robles Hospital, Neurology, Thousand Oaks, USA
13University of Maryland, Radiology, Baltimore, USA
14Advocate Health, Radiology, Oak Lawn, USA
15CHU Lille, Radiology, Lille, France
16UPMC, Neurology, Pittsburgh, USA
17Drexel Neurosciences Institute, Neurosurgery, Philadelphia, USA
Background and Aims: The current level-1a evidence for stroke thrombectomy supports a stringent 6-hour time window. The DAWN RCT which assessed the benefit of thrombectomy in strictly-selected patients treated within 6–24-hours was recently stopped after reaching its early efficacy endpoint. We aim to evaluate the safety/efficacy of thrombectomy in a large prospective cohort of late-presenting patients treated outside the more rigid clinical trial setting.
Method: Consecutive Trevo Registry patients fulfilling the basic DAWN trial criteria (ICA and/or MCA-M1 occlusion with pre-morbid mRS0-1) were categorized according to their time-from-last-seen-well to arterial puncture as early (≤6hours) vs. late (6–24hours). Univariate analyses were performed for group comparisons. Multivariate analysis was performed to identify the predictors of good outcomes (pre-specified primary endpoint).
Results: A total of 982 Trevo Registry patients (overall n = 1846; period:November/2013-March/2017) qualified for the analysis. As compared to the early-treated patients (n = 675), patients treated >6hours (n = 307) were slightly younger (median, 67 vs. 69 years, p = 0.032), had slightly milder strokes (mean admission-NIHSS, 14.9 ± 6.6 vs. 16.2 ± 5.8, p = 0.004), less often received IV t-PA (21.2% vs. 71.5%, p < 0.0001), and had higher rates of intracranial-ICA occlusions (29.6% vs. 21.9%, p = 0.002), extracranial carotid disease (9.2% vs. 5.2%, p = 0.024), right-hemispheric occlusions (53.4% vs. 47.4%, p = 0.012) and active smoking (26.6% vs. 18%, p = 0.003). Baseline and procedural characteristics were otherwise similar.
Despite significantly longer time to treatment (mean,14.1 ± 22.2 vs. 3.5 ± 1.3; median[IQR], 9.6[7.3–14.4] vs. 3.5 [2.6–4.4], p < 0.0001; >12hours:37.3% vs. 0%), late-treated patients had similar rates of reperfusion (mTICI 2b-3,95.4% vs. 93.2%, p = 0.20), good outcomes (90-day mRS0-2,59.5% vs. 59.7%, p = 1.0), symptomatic intracranial hemorrhage (1% vs. 1.3%, p = 0.76), and 90-day-mortality (9.5% vs. 9.9%, p = 0.90). Age (OR, 0.975; 95%CI [0.964–0.986]; p < 0.0001) and admission-NIHSS (OR, 0.887 [0.862–0.912]; p < 0.0001) but not time to treatment (OR, 0.997 [0.985–1.009], p = 0.62) were independent predictors of good outcomes.
Conclusion: Our study reinforces the DAWN trial approach and provides favorable generalizability data for thrombectomy within the 6–24-hour window in the “real-world” scenario.
A RANDOMISED, PLACEBO-CONTROLLED PHASE 2 TRIAL OF SUBCUTANEOUS INTERLEUKIN-1 RECEPTOR ANTAGONIST IN ACUTE ISCHAEMIC STROKE (SCIL-STROKE)
C. Smith1, S. Hulme2, A. Vail3, A. Parry-Jones2, S. Allan4, N. Rothwell4, S. Hopkins2 and P. Tyrrell2
1Manchester Academic Health Science Centre, Cardiovascular Domain, Manchester, United Kingdom
2University of Manchester, Faculty of Biology- Medicine and Health, Manchester, United Kingdom
3University of Manchester, Division of Population Health, Manchester, United Kingdom
4University of Manchester, Division of Neuroscience & Experimental Psychology, Manchester, United Kingdom
Background and Aims: The pro-inflammatory cytokine interleukin-1 (IL-1) has a deleterious role in the pathophysiology of cerebral ischaemia. Administration of IL-1 receptor antagonist (IL-1Ra) markedly attenuates experimental brain injury and is safe and well tolerated. Our objective was to investigate whether subcutaneous (SC) IL-1Ra reduces the peripheral inflammatory response in acute ischaemic stroke.
Method: SCIL-STROKE was a single-centre, double-blind, randomised, placebo-controlled phase 2 study of SC IL-1Ra 100 mg administered twice daily for three days in patients presenting within 5 h of ischaemic stroke onset. Randomisation was stratified for baseline NIHSS score and thrombolysis. Blood sampling for measurement of plasma interleukin-6 (IL-6) and other peripheral inflammatory markers was undertaken at 5 time points. The primary outcome was reduction in concentrations of IL-6 to day 3. Secondary clinical outcomes of survival, length of hospital stay and mRS were recorded at 3 months. Thirty patients per group were required for 80% power at the 5% significance level to detect a difference of 0.75 SD in the primary outcome. We planned to recruit up to 80 patients in total over 30 months to allow for loss to follow-up.
Results: Recruitment has completed with n = 80 patients randomised and final 3 month follow-up due in January 2017. This is a placeholder abstract in preparation for presentation of the results of the primary and secondary analyses in a late-breaking clinical trial session.
Conclusion: It is anticipated that this study will inform a definitive phase 3 multi-centre trial of SC IL-1Ra in ischaemic stroke by confirming biological proof-of-concept and providing exploratory clinical outcome data.
A RANDOMISED, PLACEBO-CONTROLLED PHASE 2 TRIAL OF SUBCUTANEOUS INTERLEUKIN-1 RECEPTOR ANTAGONIST IN ACUTE ISCHAEMIC STROKE (SCIL-STROKE)
C. Smith1, S. Hulme2, A. Vail3, A. Parry-Jones2, S. Allan4, N. Rothwell4, S. Hopkins2 and P. Tyrrell2
1Manchester Academic Health Science Centre, Cardiovascular Domain, Manchester, United Kingdom
2University of Manchester, Faculty of Biology- Medicine and Health, Manchester, United Kingdom
3University of Manchester, Division of Population Health, Manchester, United Kingdom
4University of Manchester, Division of Neuroscience & Experimental Psychology, Manchester, United Kingdom
Background and Aims: The pro-inflammatory cytokine interleukin-1 (IL-1) has a deleterious role in cerebral ischaemia. IL-1 induces peripheral inflammatory mediators, such as interleukin-6 (IL-6), which are associated with worse prognosis after ischaemic stroke. Administration of IL-1 receptor antagonist (IL-1Ra) markedly attenuates experimental brain injury. We therefore investigated whether subcutaneous (SC) IL-1Ra reduces the peripheral inflammatory response in acute ischaemic stroke.
Method: SCIL-STROKE was a single-centre, double-blind, randomised, placebo-controlled phase 2 study of SC IL-1Ra (100 mg administered twice daily for 3 days) in patients presenting within 5 h of ischaemic stroke onset. Randomisation was stratified for baseline NIHSS score (<13, ≥13) and thrombolysis. Measurement of plasma IL-6 and other peripheral inflammatory markers was undertaken at five time points. The primary outcome was difference in concentration of natural log (IL-6) as area under the curve (AUC) to Day 3, corrected for baseline pre-randomisation value.
Results: We recruited 80 patients (mean age 72 y, median NIHSS 11.8 [range 4 to 25]) of whom 73% received intravenous thrombolysis. A total of 63 participants (n = 35 placebo; n = 28 IL-1Ra) had sufficient serial blood samples for the primary analysis. IL-1Ra significantly reduced plasma IL-6 (p < 0.001) and similarly reduced plasma C-reactive protein (p < 0.001). IL-1Ra was well-tolerated, with no difference in the mean number of doses received between the allocation groups. There were no safety concerns with IL-1Ra in terms of overall serious adverse events or systemic infections.
Conclusion: Our results confirm biological proof-of-concept and inform design of a definitive phase 3 trial of SC IL-1Ra in ischaemic stroke.
Feasibility and Safety of Mild Therapeutic Hypothermia in Poor-Grade Subarachnoid Hemorrhage: a Prospective Pilot Study
S.C. Kwon1 and W. CHOI2
1Ulsan University Hospital, Neurosurgey, Ulsan, Republic of Korea
2Ulsan University Hospital, Emergency Medicine, Ulsan, Republic of Korea
Background and Aims: Therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic-ischemic brain injury. We studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after clipping or coil embolization.
Method: We enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4–5 and modified Fisher Scale 3–4). Patients were allocated randomly to either the TH group (34.5°C) or control group after successful clipping or coil embolization. Eleven patients received TH for 48 h followed by 48 h of slow rewarming. Vasospasm, delayed cerebral ischemia, functional outcome, mortality, and safety profiles were compared between groups.
Results: In the TH group, 10 of 11 (90.9%) patients had a core body temperature of < 36°C for >95% of the 48-h treatment period. Fewer patients in the TH than control group (n = 11 each) had symptomatic vasospasms (18.1% versus 36.4%, respectively) and delayed cerebral ischemia (36.3% versus 45.6%, respectively), but these differences were not statistically significant. At 3 months, 54.5% of the TH group had a good-to-moderate functional outcome (0–3 on the modified Rankin Scale) compared with 9.0% in the control group (p = 0.08). Mortality at 1 month was 36.3% in the control group compared with 0.0% in the TH group (p = 0.09). Serious adverse events were not significantly different between the groups.
Conclusion: In patients with poor-grade SAH, TH after successful emergency treatment may reduce the risk of vasospasm and delayed cerebral ischemia, improving the functional outcomes and reducing mortality. A larger randomized controlled trial may be warranted.
EFFECT OF INTENSIVE VERSUS GUIDELINE ANTIPLATELET THERAPY IN MAJOR ISCHAEMIC STROKE: DATA FROM THE TRIPLE ANTIPLATELETS FOR REDUCING DEPENDENCY IN ISCHAEMIC STROKE (TARDIS) TRIAL
P.M. Bath1, L.J. Woodhouse1, K. Flaherty1, D. Havard1, T.J. England1 and N. Sprigg1
1University of Nottingham, Stroke- Division of Clinical Neuroscience, Nottingham, United Kingdom
Background and Aims: The risk of recurrence following an ischaemic stroke (IS) or transient ischaemic attack (TIA) is high, especially immediately after the event. Since one antiplatelet agent is more effective than none, and two are superior to one, more intensive treatment might be even more effective in preventing recurrence providing bleeding does not become a limitation.
Method: TARDIS was an international prospective randomised open-label blinded-endpoint controlled parallel-group trial. Patients with acute non-cardioembolic IS or TIA were randomised to intensive antiplatelet therapy (combined aspirin, clopidogrel and dipyridamole) or guideline antiplatelets (clopidogrel alone, or combined aspirin and dipyridamole) given for 30 days. The primary outcome was recurrent cerebral events and their severity (based on modified Rankin Scale) at 90 days.
Results: 3,096 patients were enrolled from 106 sites in 4 countries between April 2009 and March 2016 (with 71% patients recruited from October 2012). Of these, 884 (29%; Intensive 447, Guideline 437) were enrolled with major stroke (NIHSS > 3). At baseline: mean age 69 (SD 10); male 64%; recruitment from UK 92%; prior stroke 14%; diabetes 21%; onset to randomisation <12 hours 8%, <24 hours 23%.
Conclusion: The results of this analysis will be available for presentation in quarter 2 2016. TARDIS is large enough to influence clinical practice.
Effect of intravenous glyburide on adjudicated edema endpoints in the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial
W.T. Kimberly1, M.B. Bevers2, R. von Kummer3, A.M. Demchuk4, J.M. Romero5, J.J. Elm6, H. Hinson7, B.J. Molyneaux8, J.M. Simard9 and K.N. Sheth10
1Massachusetts General Hospital, Neurology, Boston, USA
2Brigham & Women's Hospital, Neurology, Boston, USA
3Universitätsklinikum Carl Gustav Carus, Neuroradiology, Dresden, Germany
4University of Calgary, Clinical Neurosciences and Radiology, Calgary, Canada
5Massachusetts General Hospital, Neuroradiology, Boston, USA
6Medical University of South Carolina, Public Health Sciences, Charleston, USA
7Oregon Health Sciences University, Neurology, Portland, USA
8University of Pittsburgh Medical Center, Neurology, Pittsburgh, USA
9University of Maryland School of Medicine, Neurosurgery, Baltimore, USA
10Yale New Haven Hospital, Neurology, New Haven, USA
Background and Aims: The GAMES-RP trial tested intravenous (IV) glyburide for the prevention of edema in large hemispheric infarction patients. The primary objective of this analysis was to evaluate the effect of IV glyburide on adjudicated, edema-related endpoints.
Method: GAMES-RP was a prospective, double blind, randomized, placebo controlled phase 2 study that enrolled patients with large hemispheric infarction. Blinded adjudicators assigned designations for edema and edema-related endpoints, including neurological deterioration, malignant edema and edema-related death using a priori definitions.
Results: In the per protocol sample, there was no difference in the incidence of malignant edema (46% in IV glyburide; 47% in placebo, p = 0.94) or edema-related neurological deterioration (45% IV glyburide; 50% placebo, p = 0.66). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (2.4% IV glyburide; 22.2% placebo, p = 0.01). Moreover, in patients who experienced malignant edema or edema-related neurological deterioration, there was less midline shift and reduced MMP-9 levels. The rate of NIHSS increase of ≥ 4 during the infusion period (37% IV glyburide; 71% in placebo, p = 0.043), and the change in level of alertness (NIHSS subscore 1a; 58% versus 94%; p = 0.016] also favored IV glyburide.
Conclusion: IV glyburide was associated with fewer deaths attributed to edema. Interpretation of the rates of malignant edema and neurological deterioration may be confounded by a ceiling effect in severe stroke patients. However, IV glyburide treatment was associated with improvements in midline shift, MMP-9, NIHSS and level of alertness. These data support further study of IV glyburide in a phase 3 trial.
Head positioning in high risk patients: post-hoc subgroup analysis of HeadPoST, an international cluster crossover trial
P. Lavados1, V. Olavarria1, M. Hackett2, A. Brunser1, P. Muñoz-Venturell1, H. Arima3, T. Robinson4, S. Middleton5, L. Billot6, C. Watkins7 and C. Anderson8
1Clinica Alemana - Universidad del Desarrollo - Instituto de Neurociencias, Departamento de Neurología y Psiquiatría, Santiago, Chile
2The George Institute for Global Health- University of Sydney- Sydney, School of Health- University of Central Lancashire- Preston- Lancashire- UK., Sydney, Australia
3The George Institute for Global Health- University of Sydney- Sydney, Department of Preventive Medicine and Public Health- Faculty of Medicine- Fukuoka University- Fukuoka- Japan, Fukuoka, Japan
4NIHR Biomedical Research Unit for Cardiovascular Sciences- University of Leicester, Department of Cardiovascular Sciences, Leicester, United Kingdom
5Nursing Research Institute, St Vincents Health Australia Sydney and Australian Catholic University-, Sydney, Australia
6The George Institute for Global Health- University of Sydney- Sydney, Department of Biostatistics, Sydney, Australia
7University of Central Lancashire- Preston., School of Health, Lancashire, United Kingdom
8The George Institute for Global Health- University of Sydney- Sydney- NSW- Australia. The George Institute China at Peking University Health Science Center- Beijing- PR China, Neurology Department- Royal Prince Alfred Hospital- Sydney- NSW- Australia, Sydney, Australia
Background and Aims: The Head Positioning in Stroke Trial (HeadPoST) aimed to determine comparative effectiveness of lying-flat versus sitting-up (≥30°) in patients with acute stroke. The main results were announced and are in press, showing no between-group differences in any disability outcome or serious adverse events (SAEs) including pneumonia. We aimed to explore the effects in further subgroups at potential high risk of harm from lying flat.
Method: HeadPoST was a prospective, cluster crossover, blinded outcome clinical trial involving 11094 patients from 114 hospitals in 9 countries from 2015 to 2016. An average 49 patients were recruited to each head position phase per centre, managed to a usual care policy of positioning applied early and continued for next 24 hours after admission. Treatment effects were assessed in subgroups: reperfusion therapy (thrombolysis/thrombectomy, n = 1341), large-artery atheroma (n = 2948), intubation/ventilation (n = 361), and 3 dysphagia groups - any (n = 2045), choked/coughed on eating/drinking (n = 1560), and placed on nil-by-mouth regime (n = 976).
Results: There was no significant heterogeneity in the treatment effect in patients with large-artery occlusion or who received reperfusion treatment. However, there was an indication that the effects were different for the later two major dysphagia groups for all 3 endpoints: primary disability outcome (ordinal shift in mRS scores), any SAE and pneumonia. The differential effect consistently favoured the lying-flat position.
Conclusion: Secondary analysis of the HeadPoST study suggest differential treatments between lying-flat and sitting-up in patients with dysphagia who are assesses as high risk of aspiration.
SAFETY AND EFFICACY OF INTRA-ARTERIAL INFUSION OF BONE MARROW DERIVED MONONUCLEAR CELLS IN SUBACUTE ISCHEMIC STROKE: RANDOMIZED OPEN LABELED CLINICAL TRIAL
D. Khurana1, R. Singh1, V. Gupta2, R. Sharma3 and N. Khandelwal2
1Postgraduate Institute of Medical Education and Research, Neurology, Chandigarh, India
2Postgraduate Institute of Medical Education and Research, Radiodiagnosis, Chandigarh, India
3Postgraduate Institute of Medical Education and Research, Transfusion Medicine, Chandigarh, India
Background and Aims: Stem cells activate and amplify endogenous restorative brain plasticity process. Bone marrow derived mononuclear stem cells (BMSCs) induce changes in serum cytokines and growth factors. Safety, improved outcomes and reductions in lesion volume with stem cells has been observed.
Aim:To assess safety and clinical outcome of intraarterial infusion of bone marrow derived mononuclear cells in subacute ischemic stroke patients
Method: Prospective randomized open label blinded end point assessment was carried out on five cases and ten controls. Subacute ischemic stroke (Day 15–28) with NIHSS 7–15 were randomly assigned to receive intraarterial infusion of autologous BMSCs or standard of care. Primary outcome assessed was safety. Secondary outcomes was efficacy based on modified Rankin scale (mRS 0–2) at day 30, 90 and 180 days.
Results: Patients received mean of 4.16x107 CD 34 positive BMSCs injected in ipsilateral M1 MCA. 231 subjects were screened and 22 randomised Six in BMSC and one control withdrew consent after randomization. Mean age was 61.4 + 12.4yrs, Median NIHSS 12. Median time from onset to cell infusion was 22 days (IQR:15.00 – 39.50),from bone marrow aspiration to infusion-3.20 (IQR 0.4) hours.
No adverse event was observed during infusion and follow up. No difference was observed in outcomes based on mRS (0–2 at 180 days),BI or NIHSS(p = .534). Two patients died in control arm. No change seen in infarct volume (−3.3 versus −3.37; P = 0.95) at day 180. No adverse events observed in two arms
Conclusion: Intra-arterial infusion of BMSCs is safe in subacute ischemic strokes. Study was not powered for clinical efficacy which should be tested in adequately powered study.
INTRATHECAL BACLOFEN THERAPY COMPARED TO THE CONVENTIONAL TREATMENT: EFFICACY RESULTS IN THE MANAGEMENT OF POST-STROKE SPASTICITY OF THE SISTERS RANDOMIZED CONTROL TRIAL
M. Creamer1, G. Cloud2, P. Kossmehl3, M. Yochelson4, G. Francisco5, A. Ward6, J. Wissel7, M. Zampolini8, M. Loven9, N. Berthuy10, A. Abouihia10, A. Calabrese10 and L. Saltuari11,12
1Central Florida Pain Relief Centers, ., Orlando, USA
2St George’s University Hospitals NHS Foundation Trust, ., London, United Kingdom
11Landeskrankenhaus Hochzirl, Abteilung für Neurologie, Zirl, Austria
12Research Unit for Neurorehabilitation South Tyrol, ., Bolzano, Italy
Background and Aims: AS03-019 Intrathecal Baclofen (ITB) is an effective treatment for managing severe spasticity in post-stroke patients. SISTERS, a randomized, controlled, open-label multicenter study compared the efficacy of the ITB therapy versus oral anti-spastic medications (Best Medical Treatment, BMT) in severe spasticity patients.
Method: Sixty stroke patients who presented with spasticity in at least two extremities and an Ashworth Scale (AS) score ≥3 in a minimum of two affected muscle groups in the lower limbs were randomized to ITB or BMT arms and evaluated after 6 months of treatment.
Results: At baseline mean (SD) age and time since stroke were 55.89 (9.90) and 4.76 (3.62) years, respectively. After 6 months of treatment the mean AS in the affected lower limbs decreased by 0.99 (0.75) in the ITB group compared to 0.43 (0.72) in the BMT patients (P < 0.05). Decrease of AS in upper extremities was 0.66 (0.59) versus 0.17 (0.70) in ITB and BMT groups, respectively (P < 0.05). In addition, patients in the ITB arm showed an improvement of 2.68 (10.31) in the Functional Independence Measure. Seven serious adverse drug reactions (SADR, constipation, fecaloma, epilepsy, peripheral edema, hypotension, 2 urinary retention) and 4 serious device reactions (device dislocation, infection, catheter occlusion, intracranial hypotension) were observed in the implanted patients (24% and 16% of patients, respectively) versus 1 SADR (epilepsy) in the BMT group (3%). These serious events were successfully resolved.
Conclusion: This is the first clinical evidence showing superior efficacy of ITB therapy compared to conventional oral medication in decreasing spastic hypertonia in post-stroke patients.
CTX HUMAN STEM CELLS IN STROKE RECOVERY: 6 MONTH OUTCOMES OF THE PILOT INVESTIGATION OF STEM CELLS IN STROKE PHASE 2 EFFICACY (PISCES II) STUDY
D. Bulters1, M. Wilmot2, N. Sprigg3, A. Dixit4, N. Ward5, P. Tyrrell6, A. Majid7 and K. Muir8
1University Hospital Southampton, Wessex Neurological Centre, Southampton, United Kingdom
2Queen Elizabeth Hospital Birmingham, Neurology, Birmingham, United Kingdom
3University of Nottingham, Division of Clinical Neurosccience, Nottingham, United Kingdom
4Royal Victoria Infirmary, Stroke Research, Newcastle, United Kingdom
5University College London, Stroke Research Centre, London, United Kingdom
6University of Manchester, Institute of Cardiovascular Science, Manchester, United Kingdom
7University of Sheffield, Department of Neurosciences, Sheffield, United Kingdom
8University of Glasgow, Institute of Neuroscience & Psychology, Glasgow, United Kingdom
Background and Aims: PISCES 2 is an open label single arm study (2012-003482-18) undertaken to determine whether a sufficient proportion of patients with upper limb dysfunction exhibit improvement in arm function following intracranial implantation of CTX cell therapy to justify a randomised controlled trial.
Method: Patients with supratentorial ischaemic stroke resulting in upper limb weakness (NIHSS > 1) and functional impairment (Action Research Arm Test [ARAT] sub-test number 2 [grasp] 0–1) were recruited 1 to 10 months post-stroke onset. A single dose of 20 million CTX cells was injected by stereotactic surgery into the putamen of the affected hemisphere. Patients were assessed prior to, and at 1, 3, 6, and 12 months post-cell administration.
The primary outcome was a ≥ 2 point improvement in ARAT sub-test 2, at 3 months post-cell administration. Secondary outcomes included changes in ARAT total score, modified Rankin Scale, Barthel Index and Fugl-Meyer scale along with safety and tolerability. Responder analysis for minimal clinically important differences of the secondary outcome measures was undertaken.
Results: Twenty three patients were treated at a median of 7 (IQR 6–11.5) months after stroke onset, 52% male, mean age 65 years (range 41–79). Median NIHSS at enrolment was 7 (IQR 5–8).
Results of Responder Analysis
ARAT subtest = 2 point n = 23
ARAT total ≥ 6 point improvement n = 23
mRS ≥ 1 category improvement n = 23
Barthel Index (/100) ≥ 9 point improvement n = 23
Fugl-Meyer ≥ 10 point improvement (motor scale) n = 11
# Responders
3
7
7
8
3
Conclusion: Adverse events related to surgery were reported in most patients. No cell-related effects have been evident to date. Six month outcomes will be presented.
TALOS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO TEST THE VASCULAR AND NEUROPROTECTIVE EFFECTS OF CITALOPRAM IN PATIENTS WITH ACUTE ISCHEMIC STROKE
G. Andersen1, K.L. Kraglund1, J.K. Mortensen1, A.G. Lauritsen1, B. Modrau2, S.A. Simonsen3, H.K. Iversen3, M. Madsen4 and E.L. Grove5
1Aarhus University Hospital, Dept. of Neurology, Aarhus, Denmark
2Aalborg University Hospital, Dept. of Neurology, Aalborg, Denmark
3Rigshospitalet - Glostrup, Dept. of Neurology, Glostrup, Denmark
4Aarhus University Hospital, Dept. of Clinical Medicine, Aarhus, Denmark
5Aarhus University Hospital, Dept. of Cardiology, Aarhus, Denmark
Background and Aims: Selective Serotonin Reuptake Inhibitors (SSRI) are effective and safe in the treatment of post-stroke depression (PSD). SSRI may inhibit platelet aggregation and a neuroprotective effect has been suggested. However, data on the efficacy and safety of early SSRI treatment in patients with acute stroke are lacking.
The aim of this trial was to investigate whether early SSRI after ischaemic stroke has 1) a vascular protective effect and 2) an effect on functional ability at 6 months.
Method: A multicenter, randomized, double-blind, placebo-controlled study. We included 641 first-ever ischaemic stroke patients without depressive symptoms within 7 days after onset. Patients were randomized to citalopram or placebo (1:1) as add-on to standard medical care. The two co-primary outcomes were: 1) a composite end-point of vascular death, TIA/recurrent stroke or myocardial infarction and 2) modified Rankin Score (mRS). Secondary effect variables included the individual components of the combined outcome and PSD, and cognitive function.
Data will be analyzed according to the statistical analysis plan described prior to unblinding, including intention-to-treat and per-protocol analyses.
Results: In total, 545 (85%) patients (mean age 68 yrs, 34% female) received treatment for at least 1 month (per-protocol). Patients started treatment in average 2.1 days (SD 1.64) after index stroke. At baseline, NIHSS was 5.0 (SD 5.2) and mRS was comparable in the two treatment arms.
Final results will be presented at the ESOC.
Conclusion: This trial is the largest RCT so far to examine the efficacy and safety of early SSRI treatment after ischemic stroke.
AS04-003
CLINICAL TRIAL RESULTS – PREVENTION
PRASUGREL VERSUS CLOPIDOGREL IN ISCHEMIC STROKE PATIENTS: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP TRIAL (THE PRASTRO-I)
K. Toyoda1, A. Ogawa2, Y. Ikeda3, S. Uchiyama4, N. Tanahashi5, M. Matsumoto6, I. Nagata7 and K. Minematsu1
1National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine, Suita- Osaka, Japan
2Iwate Medical University, Department of Neurosurgery, Morioka- Iwate, Japan
3Waseda University, Cooperative Major in Advanced Biomedical Science, Tokyo, Japan
4International University of Health and Welfare, Clinical Research Center, Tokyo, Japan
5Saitama Medical University International Medical Center, Department of Neurology, Hidaka- Saitama, Japan
6JCHO Hoshigaoka Medical Center, Department of Neurology, Hirakata- Osaka, Japan
7Kokura Kinen Hospital, Department of Neurosurgery, Kitakyushu, Japan
Background and Aims: Prasugrel, a thienopyridine inhibitor of the platelet P2Y12 receptor, has been widely used for patients with acute coronary syndrome. However, the effects of prasugrel for stroke patients have not been clarified.
Method: The PRASTRO-I study was a phase 3, multicenter, randomized, double-blind, parallel group, trial involving 3747 patients (62 ± 9 years old, 797 women) with noncardioembolic ischemic stroke under the age of 75 years and over the body weight of 50 kg from 224 Japanese institutes (JapicCTI-111582). The patients were randomly assigned between 1 and 26 weeks after symptom onset, in a 1:1 ratio, to receive either prasugrel (3.75 mg once daily) or clopidogrel (75 mg once daily) for 96 weeks. The primary objective was to determine whether prasugrel would be noninferior (below a margin of 1.35) to clopidogrel with respect to the primary composite outcome of ischemic stroke, myocardial infarction, or other vascular death.
Results: The primary outcome occurred in 73 of 1885 (3.9%) patients receiving prasugrel, versus 69 of 1862 (3.7%) patients receiving clopidogrel (RR 1.05, 95% CI 0.76–1.44). Any stroke, as a secondary outcome, occurred in 73 patients (3.9%) for both groups (RR 0.99, 95% CI 0.72–1.36). A composite safety outcome of life-threating bleeding, major bleeding, or clinically relevant bleeding occurred in 115 (6.1%) versus 110 patients (5.9%), respectively (RR 1.02, 95% CI 0.79–1.33).
Conclusion: The study did not demonstrate noninferiority of prasugrel over clopidogrel in Japanese patient with noncardioemboric ischemic stroke, though the rates of efficacy and safety outcomes were similar between groups.
AS04-021
CLINICAL TRIAL RESULTS – PREVENTION
THE FURTHER CARDIOVASCULAR OUTCOMES RESEARCH WITH PCSK9 INHIBITOR IN SUBJECTS WITH ELEVATED RISK (FOURIER) TRIAL: EFFECT OF EVOLOCUMAB ON CEREBROVASCULAR DISEASE
T.R. Pedersen1, R.P. Giuliano2, P. Sever3, A. Keech4, S.M. Wasserman5, N. Honarpour5, H. Wang5, A. Lira Pineda5, T. Liu5 and M.S. Sabatine6
2Brigham and Women-s Hospital and Harvard Medical School, TIMI Study Group- Division of Cardiovascular Medicine, Boston, USA
3Imperial College London, International Cente for Circulatory Health, London, United Kingdom
4Sydney Medical School, NHMRC Clinical Trials Centre, Sydney, Australia
5Amgen, Clinical Research, Thousand Oaks- CA, USA
6Brigham & Women's Hospital and Harvard Medical School, TIMI Study Group- Division of Cardiovascular Medicine, Boston, USA
Background and Aims: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for ischemic cerebrovascular disease. Statins and the combination of statin and ezetimibe have been shown to reduce the risk of non-hemorrhagic stroke as well as other cardiovascular diseases. Evolocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) that reduces LDL-C by ≈ 60%. We tested the hypothesis that evolocumab and optimized statin therapy combined would reduce the incidence of major adverse cardiovascular events including ischemic cerebrovascular events.
Method: FOURIER is a randomized, double blind, placebo-controlled, multinational clinical trial. Patients with a history of myocardial infarction (MI), non-hemorrhagic stroke, or symptomatic peripheral artery disease and either an LDL-C ≥ 70 mg/dl or a non-HDL-C ≥100 mg/dl on optimized statin therapy were randomized in a 1:1 ratio to evolocumab (either 140 mg SC every 2 weeks or 420 mg SC every month according to patient preference) or matching placebo. The primary endpoint is the composite of cardiovascular death, MI, hospitalization for unstable angina, stroke, or coronary revascularization. The key secondary endpoint is the composite of cardiovascular death, MI, or stroke. Ischemic fatal and non-fatal stroke and TIA is another secondary endpoint.
Results: 27,564 patients were enrolled between February 2013 and June 2015. A total of 19% have a history of non-hemorrhagic stroke. The target of accruing at least 1630 adjudicated key secondary endpoints was achieved late 2016.
Conclusion: Details on the efficacy and safety in patients with a history of non-hemorrhagic stroke and on cerebrovascular outcomes will be ready for presentation.
LB04-001
CLINICAL TRIAL RESULTS – PREVENTION
SPACE-2: STENT-PROTECTED ANGIOPLASTY IN ASYMPTOMATIC CAROTID ARTERY STENOSIS VS. ENDARTERECTOMY COMPARED TO BEST MEDICAL TREATMENT. ONE YEAR RESULTS
T. Reiff1, H. Eckstein2, U. Mansmann3, O. Jansen4, G. Fraedrich5, H. Mudra6, D. Böckler7, M. Böhm8, H. Brückmann9, E. Debus10, J. Fiehler11, K. Mathias12, E. B. Ringelstein13, J. Schmidli14, R. Stingele15, R. Zahn16, W. Hacke17 and P. Ringleb17
Background and Aims: (ISRCTN 78592017) Recommendations for treatment of asymptomatic carotid artery Stenosis (ACAS) with endarterectomy (CEA) are based on trials recruiting patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may have led to a decreasing stroke risk in ACAS. The aim of SPACE-2 was to compare the preventive effects of BMT alone, with that of BMT plus CEA or carotid artery stenting (CAS) in patients with ACAS ≥ 70%ECST.
Method: 513 patients were randomised to CEA (n = 203), CAS (n = 197) or BMT (n = 113). The primary efficacy end-point (any stroke or death from any cause within 30 days plus ipsilateral ischaemic stroke within 5 years) and further end-points were analysed.
Results: Study was stopped prematurely because of recruitment problems. One-year-rate of the primary endpoint was not significantly different between groups (BMT 0.9%, CEA 2.5%, CAS 3.1%; p = 0.473). Rates of any stroke (BMT 0.9%, CEA 3.9%, CAS 3.6%, p = 0.312). and mortality did not differ significantly between groups (BMT 3.5%, CEA 2.5%, CAS 1.0%; p = 0.304). Higher rates of restenosis occurred in the stenting group (CAS 5.1% vs. CEA 2.0%, p = 0.108).
Conclusion: These interim results from SPACE-2 did not show that CAS or CEA are superior to BMT in primary stroke prevention in patients with a ACAS up to one year after treatment. CAS did not differ significantly from CEA in terms of safety and efficacy in treating ACAS. Follow-up will be performed up to 5 years. Data may be used for pooled analysis with ongoing trials.
LB04-002
CLINICAL TRIAL RESULTS – PREVENTION
CILOSTAZOL VERSUS ASPIRIN FOR A COGNITIVE OUTCOME IN ISCHEMIC STROKE PATIENTS WITH HIGH RISK OF CEREBRAL HEMORRHAGE: PICASSO-COG TRIAL
B. C.Lee1, J. S. Lim1, K. S. Hong2, M. S. Oh1, J. Lee3, J. M. Choi3, J. S. Lee4, S. U. Kwon5 and K. H. Yu1
1Hallym University Sacred Heart Hospital- Hallym University College of Medicine, Department of Neurology, Anyang, Republic of Korea
2Inje University Ilsan Paik Hospital- Inje University College of Medicine, Department of Neurology, Goyang, Republic of Korea
3Korea University College of Medicine, Department of Biostatistics, Seoul, Republic of Korea
4Clinical Trial Center- Asan Medical Center, Department of Biostatistics, Seoul, Republic of Korea
5Asan Medical Center- University of Ulsan College of Medicine, Department of Neurology, Seoul, Republic of Korea
Background and Aims: Multiple cerebral microbleeds (CMBs) and prior intracerebral hemorrhage (ICH) are associated with higher risk of cognitive decline after stroke. We aimed to investigate the differences of cilostazol and aspirin to prevent cognitive decline in stroke patients with multiple CMBs or prior ICH.
Method: PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage for reducing COGnitive decline (PICASSO-COG) is a randomized controlled trial with 61 institutes from South Korea. Patients with noncardioembolic ischemic stroke within 180 days with previous ICH or multiple CMBs were randomized to cilostazol versus aspirin groups. Mini-mental state examination (MMSE) was conducted at 4 (baseline), 13, 25, 37, and 49 months after index-stroke. Primary outcome was the change in MMSE score over time from baseline, which was analyzed using mixed effects model.
Results: A total 892 subjects were included in the analysis, with a median follow-up of 20.9 months. Mean changes of MMSE from baseline to each follow-up was 0.02 ± 2.45 (1st, n = 888), −0.15 ± 2.65 (2nd, n = 593), −0.24 ± 3.11 (3rd, n = 361), and −0.88 ± 3.06 (4th, n = 138). Changes in MMSE scores over time did not differ between treatment groups (Figure). Subgroup and sensitivity analyses also showed negative results.
Conclusion: There were no significant differences with cilostazol and aspirin to prevent cognitive decline after stroke in patients with high risk of cerebral hemorrhage.
AS06-048
SYSTEMATIC REVIEW AND META-ANALYSIS
RESUMPTION OF ORAL ANTICOAGULATION AFTER INTRACEREBRAL HEMORRHAGE IS ASSOCIATED WITH DECREASED MORTALITY AND FAVORABLE FUNCTIONAL OUTCOME
A. Biffi1, J. B. Kuramatsu2, A. Leasure3, H. Kamel4, C. Kourkoulis1, K. Schwab1, A.M. Ayres1, J. El5, S.M. Greenberg1, A. Viswanathan1, C.D. Anders1, S. Schwab2, J. Rosand1, F.D. Testai6, D. Woo7, H.B. Huttner2 and K.N. Sheth3
1Massachusetts General Hospital, Neurology, Boston- MA, USA
3Yale University School of Medicine, Neurology, New Haven- CT, USA
4Weill Cornell College of Medicine, Neurology, New York- NY, USA
5Medical University of South Carolina, Public Health Sciences, Charleston- SC, USA
6University of Illinois College of Medicine, Neurology and Rehabilitation, Chicago- IL, USA
7University of Cincinnati, Neurology and Rehabilitation Medicine, Cincinnati- OH, USA
Background and Aims: Oral-Anticoagulation-Treatment (OAT) resumption is a dilemma in Intracerebral Hemorrhage (ICH) care, particularly for lobar hemorrhages related to Cerebral-Amyloid-Angiopathy. We sought to determine whether OAT resumption after ICH is associated with decreased mortality and favorable long-term outcome, accounting for ICH location (i.e. lobar vs. non-lobar).
Method: We meta-analyzed individual-patient-data from: 1) the multi-center-RETRACE study conducted in Germany (n = 542); 2) a longitudinal ICH study conducted in Boston (n = 268); 3) the Ethnic/Racial-Variations-of-Intracerebral-Hemorrhage (ERICH) study (n = 217). We determined whether, at one year from ICH, OAT resumption was associated with: 1) mortality; 2) favorable functional outcome (mRS:0–3); stroke incidence. We separately analyzed non-lobar and lobar ICH cases using propensity score matching and multivariable (Cox regression) models.
Results: We included 1027 survivors of OAT-related ICH (641 non-lobar and 386 lobar). Among non-lobar ICH survivors 179/641(28%) resumed OAT, while 88/386(23%) lobar ICH survivors did. In multivariable analyses OAT resumption after non-lobar ICH was associated with decreased mortality (HR = 0.22, 95%CI = 0.16–0.30, p < 0.0001) and improved functional outcome (HR = 5.12, 95%CI = 3.86–6.80, p < 0.0001) at one year. OAT resumption after lobar ICH was also associated with decreased mortality (HR = 0.25, 95%CI = 0.17–0.38, p < 0.0001) and favorable functional outcome (HR = 4.89, 95%CI = 3.25–7.36, p < 0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar ICH (HR = 0.51, 95%CI = 0.32–0.80, p = 0.004) and non-lobar ICH (HR = 0.45, 95%CI = 0.28–0.71, p = 0.0008).
Conclusion: We provide novel evidence of association between OAT resumption, decreased mortality, and favorable outcome following ICH, regardless of hematoma location. We also identified an association between OAT resumption and decreased stroke incidence after both non-lobar and lobar ICH. These findings support conducting randomized clinical trials to explore risks and benefits of OAT resumption after ICH.
AS06-016
SYSTEMATIC REVIEW AND META-ANALYSIS
LONG-TERM ANTITHROMBOTIC TREATMENT IN INTRACRANIAL HEMORRHAGE SURVIVORS WITH ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
E. Korompoki1, F. Filippidis2, P. Nielsen3, A. Del Giudice1, G. Lip4, J. Kuramatsu5, H. Huttner5, J. Fang6, S. Schulman7, J. Martí-Fàbregas8, C. Gathier9, A. Viswanathan10, A. Biffi10, D. Poli11, C. Weimar12, U. Malzahn13, P. Heuschmann14 and R. Veltkamp1
1Imperial College London, Department of Stroke Medicine, London, United Kingdom
2Imperial College London, Department of Primary Care and Public Health, London, United Kingdom
3Aalborg Thrombosis Research Unit- Aalborg University, Department of Clinical Medicine- Faculty of Medicine, Aalborg, Denmark
4University of Birmingham- Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom
5University of Erlangen-Nuremberg, Department of Neurology, Erlangen-Nuremberg, Germany
6Institute for Clinical Evaluative Sciences, ICES, Toronto, Canada
7Thrombosis and Atherosclerosis Research Institute, Department of Medicine- McMaster University, Hamilton- Ontario, Canada
8Hospital de la Santa Creu i Sant Pau- IIB-Sant Pau, Stroke Unit- Department of Neurology, Barcelona, Spain
9Brain Center Rudolf Magnus- University Medical Center Utrecht, Department of Neurology and Neurosurgery, Utrecht, The Netherlands
10Massachusetts General Hospital- Harvard Medical School, Department of Neurology, Boston- Massachusetts, USA
11Careggi Hospital, Thrombosis Center, Florence, Italy
12University Hospital of Duisburg-Essen, Department of Neurology, Duisburg-Essen, Germany
13University Hospital Würzburg, Clinical Trial Center Würzburg, Würzburg, Germany
14Institute of Clinical Epidemiology and Biometry- University Würzburg, Comprehensive Heart Failure Center, Würzburg, Germany
Background and Aims: The risk-benefit ratio of antithrombotic therapies for stroke prevention in intracranial haemorrhage (ICH) survivors with atrial fibrillation (AF) remains unknown. We performed a systematic review and meta-analysis of studies reporting recurrent ICH and ischemic stroke (IS) in ICH survivors with AF during long-term follow-up.
Method: A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the PRISMA statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKA), antiplatelet agents (APA) or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RR) were conducted using the inverse variance method.
Results: 17 articles met inclusion criteria. Seven observational studies enrolling 2452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKA compared to APA (RR = 0.45, 95% CI: 0.27–0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI: 0.29–0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA RR = 1.34; 95% CI: 0.79 to 2.30, p = 0.28; VKA vs no-ATM RR = 0.93, 95% CI: 0.45 to 1.90, p = 0.84).
Conclusion: In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence substantially. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.
AS08-004
THROMBOLYSIS – EXCLUDING CLINICAL TRIAL RESULTS
MILD STROKE DUE TO LARGE ARTERY OCCLUSION. WHEN IS IV THROMBOLYSIS NOT ENOUGH? RESULTS FROM THE SITS-ISTR REGISTRY
M. Mazya1, C. Cooray1, K.R. Lees2, G.A. Ford3, M. Bar4, S. Frol5, T.P. Moreira1, L. Sekaran6, V. Švigelj5, D. Toni7, N. Wahlgren8 and N. Ahmed1
1Karolinska University Hospital, Department of Neurology, Stockholm, Sweden
2University of Glasgow, Institute of Cardiovascular and Medical Sciences-, Glasgow, United Kingdom
3Oxford University Hospitals NHS Foundation Trust, Acute Stroke Service, Oxford, United Kingdom
4University Ostrava, Department of neurology- Faculty Hospital and Faculty of Medicine, Ostrava, Czech Republic
5University Medical Center Ljubljana, Department of Vascular Neurology and Neurological Intensive Care, Ljubljana, Slovenia
6Luton & Dunstable NHSFT University Hospital, Stroke Service, Luton, United Kingdom
7University of Rome- 'La Sapienza', Department of Neurology and Psychiatry, Rome, Italy
8Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden
Background and Aims: We aimed to determine the frequency, risk factors and 3 month outcomes of non-hemorrhagic early neurological deterioration (nhEND) in patients suffering IVT-treated minor stroke, with versus without associated occlusion of large proximal and distal cerebral arteries.
Method: We analysed data from the SITS-International Stroke Thrombolysis Register on 2553 patients with IVT-treated minor stroke (NIH Stroke Scale (NIHSS) scores 0–5) and available arterial occlusion data. nhEND was defined as an increase in NIHSS score ≥ 4 at 24 hours, without parenchymal hematoma on follow-up imaging within 22–36 hours. Adjusted OR were determined for groups with LAO compared to those with no occlusion.
Results: Frequency of nhEND diminished from 30% of patients with terminal internal carotid (ICA-T) or tandem occlusions (ICA + middle cerebral artery (MCA) (adjusted OR: 10.3, p < 0.001), through 17% in extracranial carotid occlusions (aOR 4.3, p < 0.001) and 9% (aOR 2.1, p = 0.06) with proximal MCA-M1 occlusion, to only 3.1% in those without occlusion. Death or dependency (mRS 3–6) at 3 months occurred in 77% (95% CI 60.2–88.6%) of patients with any occlusion and nhEND, in 10.9% (8.2–14.5%) in occlusion without nhEND and in 10.8% (9.2–12.6%) of patients without occlusion.
Conclusion: Patients with apparently minor stroke associated with occlusion of the ICA, with or without tandem MCA involvement, are at high risk of disabling deterioration, despite IVT treatment. Acute vessel imaging is desirable even in minor stroke patients to identify and consider endovascular treatment for those who may be at high risk of preventable deterioration.
Early Prolonged Ambulatory Cardiac Monitoring in Stroke (EPACS): Randomised Clinical Trial using patch-based cardiac monitoring
J. Teo1, A. Kaura2, L. Sztriha1, J. Aeron-Thomas1, F. K. Chan1, P. Rao1, E. McKenzie1, B. Chitando1, J. Lenane3, N. Gall2 and B. Piechowski-Jozwiak1
1King's College Hospital NHS Foundation Trust, Stroke & Neurology, London, United Kingdom
2King's College Hospital NHS Foundation Trust, Cardiology, London, United Kingdom
3iRhythm Technologies Inc., iRhythm Technologies Inc., San Francisco, USA
Background and Aims: Cardioembolism in paroxysmal atrial fibrillation (PAF) is a preventable cause of ischaemic stroke or transient ischaemic attack (TIA), but the transient nature of PAF means that a short-duration Holter monitor misses a significant proportion of cases. Systems for recording beyond 3–7 days have significant limitations: event-triggered loop recorders are cumbersome while implanted loop recorders require a minor surgical procedure. There is a need for patient-friendly long-duration cardiac monitoring systems for stroke patients.
Method: Pragmatic randomised controlled trial of cardiac monitoring after an ischaemic stroke or TIA (recruited <3 days of index event) randomised 1:1 to use either a wearable water-proof adhesive cardiac monitoring patch (Zio® Patch, iRhythm Technologies Inc) fitted immediately by the clinician early after the index event or a standard Holter ECG. ISCRTN Registration 50253271. The total patients recruited was 120 patients across two hospital sites with large stroke units:
• Kings College Hospital, London (urban teaching hospital)
• Princess Royal University Hospital (suburban district hospital)
Results: The interim analysis of the first 87 patients should more PAF in the active arm which had not yet reached statistical significance in January 2017. Those in the control arm of Holter ECG's had significant delays to initiate cardiac monitoring due to scheduling delays and patient non-attendance. There were no device-attributable serious adverse events. Late-breaking results with the full target study population will be presented.
Conclusion: The convenience of the patch-based cardiac monitor substantially increased the uptake and efficiency of cardiac monitoring early after ischaemic strokes and TIA, and may have superior PAF detection rate to standard approaches.
AS21-056
IMAGING – HYPERACUTE
COMPARING THE IMPACT OF BASELINE COLLATERAL STATUS ASSESSED BY DIFFERENT COLLATERAL SCORES AND IMAGING MODALITIES ON OUTCOMES IN ACUTE ISCHEMIC PATIENTS: META-ANALYSIS FROM THE HERMES-COLLABORATION
H. Gensicke1, F. Al Ajlan2, B. Campbell3, C. Majoie4, S. Bracard5, K. Muir6, L. S. Román7, A. Van Der Lugt8, D. Liebeskind9, S. Brown10, P. White11, F. Guillemin12, A. Dávalos13, T. Jovin14, J. Saver15, M. Hill2, D. Dippel8, P. Mitchell16, A. Demchuk2 and B. Menon2
1Stroke Center and Department of Neurology, University Hospital Basel, Switzerland
2Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary AB, Canada
3Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
4Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands
5Department of Diagnostic and Interventional Neuroradiology, University Hospital of Nancy, INSERM U 947, Nancy, France
6Institute of Neuroscience & Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK
7Department of Radiology, Hospital Clínic, Barcelona, Spain
8Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands
9Neurovascular Imaging Research Core, Department of Neurology, UCLA, Los Angeles, USA
10Altair Biostatistics, St Louis Park, Minnesota
11Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
12Department of Clinical Epidemiology, INSERM CIC-EC1433, University of Lorraine and University Hospital of Nancy, Nancy, France
13Department of Neurology, Hospital Germans Trias i Pujol, Barcelona, Spain
14Stroke Institute, Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh
15Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California
16Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
Background and Aims: Good leptomeningeal collaterals are associated with smaller infarct volumes, higher rates of recanalization and improved functional outcome after acute stroke treatment (Endovascular therapy [EVT] and/or intravenous tPA [IVT]). However, assessment of collateral status on acute imaging is not standardized and the impact of imaging type and scan quality on collateral grading is poorly understood. The aim of this study is to compare different CTA/MRA based collateral scores and imaging modalities.
Method: Patients from the HERMES collaboration (Highly Effective Reperfusion evaluated in the Multiple Endovascular Stroke Trials) will be included in this pre-specified pooled meta-analysis. Collateral status will be assessed on single and multi-phase CTA and on MRA (TOF or CE) using the following collateral scoring systems: TAN Score, modified TAN Score, Regional Collateral Score for (i) single phase and (ii) multiphase CTA and the Regional Leptomeningeal (ASPECTS) Score. Scan quality will be assessed using multiple parameters including timing of acquisition, coverage, motion artifacts etc. Collateral scores and imaging modalities will be compared to each other in discrimination of imaging (infarct volumes and ASPECTS on follow-up scans) and clinical (dichotomized modified Rankin Scale [mRS) and mRS shift at 90 days) outcomes using Receiver operating curve analysis (ROC), Akaike information criterion (AIC) and Bayesian information criterion (BIC). Sensitivity analyses correcting for acquisition phase will be attempted. Imaging analysis is complete and final results will be presented.
Results: Placeholder abstract
Conclusion: Placeholder abstract
A complete author's list will be send by mail.
LB30-001
ONGOING TRIALS
DIAGNOSIS OF COGNITIVE FUNCTIONS: PROBLEMS AND PROSPECTS
I. Shvetsova1, S. Prokopenko2 and Y. Mozheiko2
1Siberian Clinical Center, Department of neurological diseases with the course of medical rehabilitation, Krasnoyarsk, Russia
2Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Department of neurological diseases with the course of medical rehabilitation, Krasnoyarsk, Russia
Background and Aims: to study pre-clinical abnormalities of visualspatial gnosis using computer method of 3D rotating object recognition.
Method: 90 subjects. Group I – young people with normal cognitive status. Group II – healthy middle-aged people. Group III – patients after stroke with mild cognitive impairment. Cognitive function condition was assessed using the mini-mental state examination (MMSE), frontal assessment battery (FAB) and the clock drawing test (CDT), The Montreal cognitive assessment (MoCA), neuropsychological testing by A. R. Luria. Visuospatial and object perception was assessed using a new, specially designed computer assessment tool of three-dimensional recognition of rotating objects. Diagnostic criteria include the speed of the object recognition in different projections and an angle of the object location in the axes X, Y, Z in the moment of recognition recorded by the software.
Results: Slower speed of recognizing both two- and three-dimensional objects was revealed in Group II and Group III. When presented with three-dimensional objects, healthy middle-aged people demonstrated later recognition, with the value of the angle of view 20–30% larger than Group I. The qualitative and quantitative assessment of the cognitive functions I and II groups of subjects characterized by the norm/ When presented with three-dimensional objects, patients after stroke demonstrated later recognition, with the value of the angle of view 49% (axis X), 41% (axis Y) and 36% (axis Z) larger than Group II.
Conclusion: Diagnostic criteria of this new method correlate with clinical manifestations in post-stroke patients, as well as show the early signs of visuospatial impairment in healthy subjects.
LB30-002
ONGOING TRIALS
The dynamics of intracranial, mean arterial and cerebral perfusion pressure by changing the position of the head patients with subarachnoid hemorrhages
N. Likholetova1 and V. Gorbachev1
1Irkutsk State Medical Academy of Postgraduate Education – Branch Campus of the F, Anaesthesiology, Irkutsk, Russia
Background and Aims: There is not defined the optimal position of the head in patients with subarachnoid hemorrhage (SAH). We stadied dynamics of intracranial (ICP), cerebral perfusion (CPP) and mean arterial pressure (MAP) by changing the position of the head at patients with SAH.
Method: 74 patients with SAH were studied. Multimodal monitoring includes ICP, MAP and CPP measurement. At the beginning baseline values were obtained in a position 30°, then was lowered by horizontal position (0°), after that elevated by 60°, and at the end was lowered to 30°.
Results: ICP in the horizontal position were 33% higher, than at 30 and 60° in the first day. Minimal values of CPP were registered at 30°. In 60° CPP was on 5,5% higher, than at 30° and reached 91 (81,5–99) mm Hg. Also in 0° at patients with SAH by 5% increased MAP. In second day maximal ICP and critically low CPP were registered in 0°. In 60° ICP was elevated for 3% and CPP decreased by 5,5% in 30°. MAP were maximal in the horizontal position. On third day the difference of values between 30° and 60° disappeared. For the fifth days ICP increase in 0°.
Conclusion: The optimum position of the first day should be considered 60°, since in this position does not increase ICP. On the second day the most favorable angle becomes 30°. By the third day of the difference metrics at position 30° and 60° disappear. On the fifth day again become a preferred 30°.
LB30-003
ONGOING TRIALS
The hospital transportation of patients with subarachnoid hemorrage
A. Lokhov1 and V. Gorbachev1
1Irkutsk State Medical Academy of Postgraduate Education – Branch Campus of the F, Anaesthesiology, Irkutsk, Russia
Background and Aims: Transportation of patients with acute cerebral pathology has its own characteristics and principles. Our aim was to optimize transportation of patients with subarachnoid hemorrhages (SAH).
Method: 60 patients with SAH (mean age - 50,39 ± 8,7 years) were studied. Cerebral blood flow (CBF) velocity in middle cerebral artery (MCA) and Lindegaard's index (LI) was estimated to five minutes before transportation and immediately after it through transcranial Doppler. Patients were divided into two groups: 50 patients were transported by the standard clinic practice. 10 patients transported using mechanical ventilation with intravenous nimodipine (1 mg / hr).
Results: In first group CBF in MCA on the operated hemisphere increased by 23.5% (from 131 (118–158) to 149 (135–170) cm / s). On the intact hemisphere CBF increase by 12% (from 120 (110–143) to 130 (117–150) cm / s). LI increase insignificantly. In second group CBF in MCA on the operated hemisphere increased by 4,5%: from 150,5 (136–177) to 153,5 (140–179) cm / s. On the intact hemisphere CBF in MCA increased by 6,2%: from 125 (115–135) to 130 (120–134) cm / s. LI decreased as the operated hemisphere (from 2,9 (2,6–3,0) to 2,7 (2,5–2,8)) and on the intact hemisphere (from 2,3 (1,8–2,7) to 2,1 (1.8–2.4)).
Conclusion: 1. During standard transportation was a significant increase CBF in MCA (23.5%) on the operated hemisphere.
2. Continuous intravenous administration of nimodipine and additional sedation in patients on mechanical ventilation can reduce the CBF increase to 4.5%.
3. Cerebral vasospasm may be regarded as an undesirable effect of transportation.
LB30-004
ONGOING TRIALS
PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke. A randomised, open, phase III, clinical trial with blinded outcome assessment
H. Reinink1, J.de Jonge1, P.M. Bath2, D. van de Beek3, E. Berge4, S. Borregaard5, A. Ciccone6, J. Demotes7, D.W. Dippel8, G. Thomalla9, H.B. van der Worp1, I. Kurkowska-Jastrzębska10, J. Kõrv11, L. Csiba12, K.R. Lees13, M.R. Macleod14, G. Ntaios15 and G. Randall16
1Brain Center Rudolf Magnus - UMC Utrecht, Department of Neurology and Neurosurgery, Utrecht, The Netherlands
2University of Nottingham, Division of Clinical Neuroscience, Nottingham, United Kingdom
3Academic Medical Center- University of Amsterdam, Department of Neurology- Amsterdam neuroscience, Amsterdam, The Netherlands
4Oslo University Hospital, Department of Internal Medicine, Oslo, Norway
5University Medical Center Hamburg-Eppendorf, CTC North GmbH & Co. KG, Hamburg, Germany
6ASST di Mantova Hospital, Department of Neurosciences, Mantua, Italy
7European Clinical Research Infrastructures Network, ECRIN, Paris, France
8Erasmus MC University Medical Center, Department of Neurology, Rotterdam, The Netherlands
9University Medical Center Hamburg-Eppendorf, Department of Neurology- Center for Clinical Neurosciences, Hamburg, Germany
10Interventional Stroke Treatment Centre, Institute of Psychiatry and Neurology, Warsaw, Poland
11University of Tartu, Department of Neurology and Neurosurgery, Tartu, Estonia
12University Medical School, Department of Neurology, Debrecen, Hungary
13University of Glasgow, Medical School and Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom
14University of Edinburgh, Department of Clinical Neurosciences, Edinburgh, United Kingdom
15University of Thessaly, Department of Medicine- Larissa University Hospital- School of Medicine, Larissa, Greece
16Stroke Alliance for Europe, SAFE, Brussels, Belgium
Background and Aims: PRECIOUS: ISRCTN82217627 - Ongoing Trial
Elderly patients are at high risk of complications after stroke, such as infections and fever. These complications are strongly and independently associated with a higher risk of death or dependency. PRECIOUS will assess whether prevention of aspiration, infections, and fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first 4 days after stroke onset improves functional outcome at 90 days in elderly patients with acute stroke.
Method: International, multi-centre, multi-factorial, randomised, controlled, open-label clinical trial with blinded outcome assessment in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated in a 2*2*2 factorial design to any combination of open-label oral, rectal, or intravenous metoclopramide (10 mg thrice daily), intravenous ceftriaxone (2000 mg once daily), oral, rectal, or intravenous paracetamol (1000 mg four times daily), or usual care, started within 12 hours after symptom onset and continued for 4 days or until complete recovery or discharge from hospital, if earlier. Investigators will have the opportunity to censor a single specific stratum in a specific patient before randomisation. The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression.
Results:Planning: First patient included May 2016; final follow-up of the last patient by April 2020
Funding: PRECIOUS is funded by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 634809.
LB30-005
ONGOING TRIALS
THE T3 TRIAL: TRIAGE, TREATMENT AND TRANSFER OF PATIENTS WITH STROKE IN EMERGENCY DEPARTMENTS
S. Middleton1, C. Levi2, S. Dale1, N.W. Cheung3, E. McInnes1, J. Considine4, C. D’Este5, D. Cadilhac6,7, J. Grimshaw8,9, R. Gerraty10,11, L. Craig1, V. Schadewaldt1, P. McElduff12, M. Fitzgerald13,14, C. Quinn15, G. Cadigan16, S. Denisenko17, M. Longworth18 and J. Ward19,20
1St Vincent’s Health Australia Sydney SVHAS and Australian Catholic University ACU, Nursing Research Institute, Sydney, Australia
2University of Newcastle, Centre for Translational Neuroscience and Mental Health, Newcastle, Australia
3University of Sydney and Westmead Hospital, Centre for Diabetes and Endocrinology Research, Sydney, Australia
4Deakin University, Nursing and Midwifery Research Centre School of Nursing and Midwifery, Burwood, Australia
5Australian National University, National Centre for Epidemiology and Population Health NCEPH, Canberra, Australia
6Monash University, Stroke and Ageing Research- School of Clinical Sciences, Clayton, Australia
7University of Melbourne, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia
8University of Ottawa, Department of Medicine, Ontario, Canada
9Ottawa Health Research Institute, Clinical Epidemiology Program, Ontario, Canada
10Monash University, Department of Medicine, Clayton, Australia
11Epworth hospital, Neurosciences Clinical Institute, Richmond, Australia
12University of Newcastle, School of Medicine and Public Health, Newcastle, Australia
13Monash University, Central Clinical School, Clayton, Australia
14Swinburne University of Technology, Faculty of Science- Engineering and Technology, Hawthorn, Australia
15Prince of Wales Hospital, Speech Pathology, Sydney, Australia
16Royal Brisbane and Women's Hospital, Statewide Stroke Clinical Network, Hertson, Australia
17Department of Health Victoria, Victorian Stroke Clinical Network, Melbourne, Australia
18Agency for Clinical Innovation, Stroke Services NSW, Sydney, Australia
19University of Ottawa, School of Epidemiology- Public Health and Preventive Medicine, Ontario, Canada
20University of Notre Dame Australia, Nulungu Research Institute, Broome, Australia
Background and Aims: Placeholder abstract number: AS01-007].
The T3 cluster randomised trial aimed to improve Triage, Treatment and Transfer (T3) of patients with acute stroke in emergency departments (EDs)
Method: Our prospective, multicentre, parallel group, cluster randomised trial with blinded outcome assessment, randomised EDs 1:1 to receive either the T3 intervention or no support (control EDs). Our evidence-based intervention targeted: (1) Triage: patients with suspected stroke assigned to Australian Triage Scale category 1 or 2 (seen within 10 minutes); (2) Treatment: screening for tPA eligibility and administration of tPA where applicable; protocols for management of fever, hyperglycaemia and swallowing; and (3) rapid Transfer from ED to the stroke unit, implemented using (i) workshops to determine barriers and solutions; (ii) education; (iii) use of clinical opinion leaders; (iv) email, telephone and site visit reminders. Primary outcome: 90-days post-admission death or dependency (mRS > 2). Secondary outcomes: 90-day: health status (SF-36), functional dependency (Barthel Index), quality of life (EQ-5D); and in-hospital quality-of-care outcomes: triage practices; monitoring and management for thrombolysis, fever, hyperglycaemia, swallowing; and transfer practices.
Results: Of the 26 eligible sites from three states and one territory in Australia, all (100%) agreed to participate with 2253 patients consenting (pre-implementation n = 645; post-implementation n = 1608). Of these, 1875 will be analysed (pre-implementation n = 574; post-implementation n = 1301). In the post-implementation cohort, 749 patients were randomised to the intervention group and 552 to the control group. Data currently are being analysed.
Conclusion: This large trial will provide rigorous evidence for assisted implementation of nurse-initiated ED stroke protocols aiming to improve outcomes for patients with stroke.
LB30-006
ONGOING TRIALS
MR CLEAN-NO IV: INTRAVENOUS TREATMENT FOLLOWED BY INTRAARTERIAL TREATMENT VERSUS DIRECT INTRAARTERIAL TREATMENT FOR ACUTE ISCHEMIC STROKE CAUSED BY A PROXIMAL INTRACRANIAL OCCLUSION
N. LeCouffe1, K. Treurniet2, J. Coutinho1, B. Emmer2, R.van Oostenbrugge3, W.van Zwam4, J. Boiten5, G. Lycklama6, K. Keizer7, L. Yo8, D. Dippel9, Y. Roos1, C. Majoie2. on behalf of the MR CLEAN NO-IV research group10
1Academic Medical Center, Neurology, Amsterdam, The Netherlands
2Academic Medical Center, Radiology, Amsterdam, The Netherlands
3Maastricht University Medical Center, Neurology, Maastricht, The Netherlands
4Maastricht University Medical Center, Radiology, Maastricht, The Netherlands
5MC Haaglanden- the Hague, Neurology, the Hague, The Netherlands
6MC Haaglanden- the Hague, Radiology, the Hague, The Netherlands
7Catharina Hospital, Neurology, Eindhoven, The Netherlands
8Catharina Hospital, Radiology, Eindhoven, The Netherlands
9Erasmus MC University Medical Center Rotterdam, Neurology, Rotterdam, The Netherlands
10MR CLEAN Centers, -, -, The Netherlands
Background and Aims: Several trials have shown that intra-arterial treatment (IAT) following intravenous alteplase (IVT) improves outcome of patients with acute ischemic stroke and a proximal intracranial occlusion. However, small subgroups of included patients had contraindications for IVT. Treatment effect of IAT in these patients was at least as effective as in patients treated with IVT prior to IAT. The question arises whether IVT is beneficial in patients eligible for IAT.
Method: The MR CLEAN-NO IV trial is a multicenter, prospective, randomized, open-label, blinded-endpoint trial, comparing IVT followed by IAT with direct IAT in patients with a confirmed occlusion of the intracranial carotid artery, M1 or proximal M2. The aim is to include 540 patients. The primary endpoint is the modified Rankin Scale score (mRs) at 90 days. Secondary endpoints include eTICI score, mortality and Barthel score at 90 days. Safety endpoints include sICH and embolization in a new territory on angiography during IAT.
The primary effect parameter is the common odds ratio of the mRs, estimated by ordinal logistic regression. We will adjust for age, pre-stroke mRs, time from onset to randomization, stroke severity and collateral score. Both superiority and non-inferiority are assessed. Secondary outcomes will be analyzed using linear, logistic or ordinal regression analyses as appropriate.
Results: Expected enrollment 1st patient July 2017.
Conclusion: We hypothesize that direct IAT may lead to an 8% absolute increase in good outcome due to a reduction in the occurrence of sICH and an increase in the treatment effect of IAT.
LB30-007
ONGOING TRIALS
PROSPECTIVE REGISTRY OF DECOMPRESSIVE SURGERY FOR CVT PATIENTS – DECOMPRESS – 2
J. FERRO1, P. CANHÃO1, J. COUTINHO2, J. STAM3, M.G. BOUSSER4 and S. Aaron5
1CHLN/University of Lisbon, Department of Neurology, LISBON, Portugal
2AMC, Department of Neurology, Amsterdam, The Netherlands
3AMC, Department of Neurolog, Amsterdam, The Netherlands
4CHU Lariboisière, Department of Neurology, PARIS, France
5Christian Medical College of Vellore, Department of Neurology, VELLORE, India
Background and Aims: Background: several retrospective registries showed that decompressive surgery is lifesaving in patients with acute severe cerebral venous thrombosis (CVT) and parenchymal lesions with impeding herniation. However, retrospective design and publication bias may overestimate the effect of the intervention. Objective: to describe in a prospective registry the vital and functional outcome of CVT patients treated by decompressive surgery, and to identify subgroups of CVT patients who benefit most from this surgery.
Method: Inclusion criteria: consecutive cases of CVT with parenchymal lesions treated by decompressive craniectomy or hematoma evacuation. Outcomes measured at 6 and 12 months by an investigator not directly involved in the surgical intervention. The opinion of the patient and main caregiver concerning the results of surgery is registered. Evaluation of cognition, mood, anxiety, Quality of life, caregiver burden and professional life is performed at 6 and 12 months follow up using MMSE, HADS, EuroQol, Expanded Caregiver Strain Index and Post Stroke working Activity Questionnaires.
Results: Sample size: we aim to collect 100 patients with the contribution of 80 recruiting centres. Primary outcome and prognostic variables: the primary outcome is the modified Rankin Scale dichotomised between favourable (0–4) and unfavourable outcome (5 or death) at last available follow up. Prognostic variables are age, delay to surgery, Glasgow Coma Scale score, fixed pupils, lesion characteristics, and type of surgery.
Conclusion: Current status: inclusion started in January 2012. By 30th March 2017, 66 centres (12 recruited) are currently participating in the study and 54 patients are already included.
LB30-008
ONGOING TRIALS
Solitaire™ With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire™ Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke (SWIFT DIRECT)
U. Fischer1, V. Mendes Pereira2, R. Chapot3, A. Siddiqui4, J. Bressan5, M. Froehler6, C. Cognard7, S. Lerch5, A. Furlan8, J. Saver9 and J. Gralla10
1University Hospital and University of Bern- Bern- Switzerland, Department of Neurology, Bern, Switzerland
2University of Toronto- Canada, Department of Neurosurgery, Toronto, Canada
3Alfried Krupp Krankenhaus- Essen- Germany, Department of Neuroradiology, Essen, Germany
4University at Buffalo- USA, Department of Neurosurgery, Buffalo, USA
5Inselspital, Department of Neurology, Bern, Switzerland
6Vanderbilt University Medical Center- USA, Department oof Neurology, Nashville, USA
7University of Toulouse- France, Department of Neuroradiology, Toulouse, France
8UH Cleveland Medical Center- USA, Department of Neurology, Cleveland, USA
9University of California- USA, Department of Neurology, Los Angeles, USA
10University Hospital and University of Bern- Bern- Switzerland, Department of Neuroradiology, Bern, Switzerland
Background and Aims: Whether pre-treatment with intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) with stent retrievers is beneficial has become a matter of debate. In a patient-level pooled analysis of five randomized controlled studies (HERMES collaboration) similar rates of functional independence and mortality at 90 days were observed between patients who received IVT + MT or MT alone. SWIFT DIRECT aims to determine, whether direct MT in patients with proximal vessel occlusion in the anterior circulation is non-inferior to IVT + MT.
Method: The international, multicentre, randomised-controlled, two-arm, open label, blinded endpoint (PROBE) trial SWIFT DIRECT will randomise 404 patients into the experimental arm (direct MT; 202) or control arm (bridging thrombolysis; 202). The trial will only be performed in patients with immediate access to MT. Main inclusion criteria are signed informed consent, age >18 and <86 years, confirmed ischaemic stroke, NIHSS ≥8 and <30 and eligibility for IVT and MT. The primary outcome is functional independence (mRS) ≤2 at 90 days. Main secondary outcomes are: mortality, change in NIHSS score post randomization, time to re-perfusion (TICI ≥ 2b) and quality of life.
Results: We will start recruitment in August 2017 with overall approximately 30 sites in Switzerland, Germany, Austria, France, Spain, Portugal and Canada.
Conclusion: If direct MT in patients with large artery vessel occlusion in the anterior circulation is as safe and efficacious as IVT + MT this would have a relevant impact on future stroke management. Maintaining a high recruitment rate will be crucial for the successful completion of the trial.
LB30-009
ONGOING TRIALS
EARLY VERSUS LATE INITIATION OF DIRECT ORAL ANTICOAGULATION IN POST-ISCHAEMIC STROKE PATIENTS WITH ATRIAL FIBRILLATION (ELAN)
U. Fischer1, M. Paciaroni2, D. Strbian3, S. Seiler4, G. Ntaios5, K. Nedeltchev6, L. Bonati7, P. Michel8, S. Lerch4, G. Thomalla9, S. Trelle10 and J. Dawson11
1Inselspital, Department of Neurology, Bern, Switzerland
2University Hospital Perugia- Perugia- Italy, Department of Internal Medicine, Perugia, Italy
3University Hospital Helsinki- Helsinki- Finland, Department of Neurology, Helsinki, Finland
4University Hospital and University of Bern- Bern- Switzerland, Department of Neurology, Bern, Switzerland
5University of Thessaly- Larissa- Greece, Department of Internal Medicine, Larissa, Greece
6Cantonal Hospital Aarau- Aarau- Switzerland, Department of Neurology, Aarau, Switzerland
7University Hospital Basel- Basel- Switzerland, Department of Neurology, Basel, Switzerland
8University Hospital Lausanne- Lausanne- Switzerland, Department of Neurology, Lausanne, Switzerland
9University Clinics Hamburg-Eppendorf, Department of Neurology, Hamburg, Germany
10University Hospital and University of Bern- Bern- Switzerland, Clinical Trial Unit, Bern, Switzerland
11University of Glasgow- Glasgow- United Kingdom, Department of Neurology, Glasgow, United Kingdom
Background and Aims: When to start anticoagulation in patients with an acute ischaemic stroke and atrial fibrillation (AF) is a relevant unanswered question in clinical practice. Direct oral anticoagulants (DOACs) are highly effective for secondary stroke prevention in these patients, but DOACs were never initiated <7 days after stroke onset in recent trials. The ELAN trial will determine the net benefit of early versus late initiation of DOACs in patients with acute ischaemic stroke related to AF.
Method: The international, multicentre, randomised-controlled, two-arm, assessor-blinded trial ELAN will randomise 2’000 patients into the experimental arm (early treatment; 1’000) or control arm (late treatment, 1’000). T DOACs initiation will vary depending on stroke size. Main inclusion criteria are signed informed consent, age >18 years, confirmed ischaemic stroke and AF and agreement of treating physician to prescribe DOACs. The primary outcome is a composite of major bleeding, recurrent ischaemic stroke, systemic embolism and/or vascular death at 30 ± 7 days after randomisation.
Results: We will start recruitment in July 2017 with currently approximately 80 sites in Switzerland and 7 other European countries.
Conclusion: This pragmatic investigator-initiated international trial will add evidence to the best time of starting DOAC after ischaemic stroke in patients with AF. If earlier initiation of DOACs in patients with ischaemic stroke related to AF is shown to be safe and efficacious, this could have a major impact on better treatment adherence, length of hospital stay and patient outcome.
LB30-010
ONGOING TRIALS
MR CLEAN MED – THE EFFECT OF PERIPROCEDURAL MEDICATION IN PATIENTS UNDERGOING INTRA-ARTERIAL TREATMENT FOR ACUTE ISCHEMIC STROKE: HEPARIN, ANTIPLATELET AGENTS, BOTH OR NEITHER
B. Roozenbeek1, V. Chalos2, A.van Es3, H. Den Hertog4, J. Staals5, L.Van Dijk6, S. Jenniskens7, A.Van der Lugt3, D. Dippel1 and On behalf of the MR CLEAN MED Investigators8
1Erasmus MC, Dept of Neurology, Rotterdam, The Netherlands
2Erasmus MC, Depts of Neurology and Public Health, Rotterdam, The Netherlands
3Erasmus MC, Dept of Radiology, Rotterdam, The Netherlands
4Medisch Spectrum Twente, Dept of Neurology, Enschede, The Netherlands
5Maastricht University Medical Centre, Department of Neurology and Cardiovascular Research Institute Maastricht CARIM, Maastricht, The Netherlands
6Hagaziekenhuis, Dept of Radiology, The Hague, The Netherlands
7Radboud University Medical Center, Dept of Radiology, Nijmegen, The Netherlands
8Collaboration for new treatments of acute stroke in the Netherlands, CONTRAST consortium, ., The Netherlands
Background and Aims: Rapid intra-arterial treatment in patients with acute ischemic stroke with confirmed proximal intracranial occlusion has been proven safe and effective. Still, many patients do not recover despite recanalization. Yet, it is unknown whether periprocedural anticoagulant medication in patients with acute ischemic stroke treated with intra-arterial treatment can improve clinical outcome. The objective of this study is to assess the effect of acetylsalicylic acid and unfractionated heparin, alone, or in combination, in patients with acute ischemic stroke who undergo intra-arterial treatment.
Method: MR CLEAN MED is a multicenter, prospective, randomized, open-label, blinded-endpoint trial using a 2x3 factorial design. We planned to enroll 1,500 patients with a clinical diagnosis of acute ischemic stroke and confirmed intracranial anterior circulation occlusion, who will undergo intra-arterial treatment with or without prior intravenous thrombolysis according to standard care. Study interventions: intravenous treatment with moderate dose unfractionated heparin (loading dose of 5000 IU followed by 1,250 IU/hour x 6 hours), low dose unfractionated heparin (loading dose of 5000 IU followed by 500 IU/hour x 6 hours) and acetylsalicylic acid (300 mg). Primary outcome is the score on the modified Rankin Scale 90 days after inclusion in the study. Safety endpoints include the occurrence of symptomatic intracerebral hemorrhage.
Results: Expected enrollment of 1st patient: July 2017.
Conclusion: We hypothesize that despite the potentially increased risk of (symptomatic) intracerebral hemorrhage, periprocedural unfractionated heparin and/or acetylsalicylic acid will improve functional outcome of patients with acute ischemic stroke treated with intra-arterial treatment.
Sponsored by the Dutch Heart Foundation.
LB30-011
ONGOING TRIALS
Multicenter Randomized Clinical Trial of Endovascular Stroke treatment in The Netherlands for Late arrivals: MR CLEAN-LATE
R.J. Goldhoorn1, R.van Oostenbrugge1, W.van Zwam1, G. Lycklama2, C. Majoie3, M. Uyttenboogaart4, M.van Walderveen5, W. Schonewille6 and M. Wermer7
1Maastricht UMC+, Neurology, Maastricht, The Netherlands
2MC Haaglanden, radiology, The Hague, The Netherlands
3Academic Medical Center, radiology, Amsterdam, The Netherlands
4University Medical Center Groningen, neurology, Groningen, The Netherlands
5University Medical Center Leiden, radiology, Leiden, The Netherlands
6St. Antonius Hospital, Neurology, Nieuwegein, The Netherlands
7University Medical Center Leiden, neurology, Leiden, The Netherlands
Background and Aims: Intra-arterial treatment (IAT) for acute ischemic stroke caused by an anterior circulation proximal intracranial occlusion, in whom the procedure can be started within 6 hours from onset, has been proven safe and effective. Currently there is no proven effective recanalization therapy beyond this 6 hour tme window. We hypothesize that IAT is effective for patients treated between 6 and 12 hours after symptom onset or last seen well less than 12 hours, after selection based on collateral flow.
Method: The MR CLEAN-LATE trial is a multicenter, prospective, randomized, open-label, blinded-endpoint trial, comparing IAT with no IAT between 6 and 12 hours after symptom onset, in acute anterior circulation ischemic stroke caused by a proximal intracranial anterior circulation occlusion (distal intracranial carotid artery or middle (M1/M2) or anterior (A1/A2) cerebral artery confirmed by neuro-imaging (CTA or MRA)). Only patients with poor, moderate, or good collateral flow will be included. The aim is to include 500 patients. Inclusion of poor collateral status will be restricted to 100 patients. The primary endpoint is the modified Rankin Scale score (mRs) at 90 days. Secondary outcomes include mortality at 90 days, hemorrhage and stroke severity at 24 hours and 5–7 days, recanalization on CTA at 24 hours and infarct size on NCCT at 5–7 days or just before discharge.
Results: Expected enrollment of the 1st patient: July 2017.
Conclusion: We expect to demonstrate a treatment effect with a shift on the mRS leading to at least an 8% difference in good outcome in favor of IAT.
LB30-012
ONGOING TRIALS
The benefit of EXtending oral antiCOAgulant treatment after acute Cerebral Vein Thrombosis (EXCOA-CVT): a cluster observational study
B. Miranda1 and J. Ferro1
1Centro Hospitalar Lisboa Norte - Hospital de Santa Maria, Neurology, Lisboa, Portugal
Background and Aims: After cerebral vein thrombosis (CVT) there is an increased risk of further venous thromboembolic events (VTEs). Guidelines suggest oral anticoagulation (OAC) for 3 to 12 months after a first episode of CVT, depending on event-related features and thrombophilic characteristics. Recommendations are extrapolated from extracerebral vein thrombosis, which may be inaccurate as the risk of thrombotic recurrence is different.
EXCOA-CVT is a prospective study with a cluster-randomised allocation design that aims to compare a policy of standard (3–6 months) versus extended (12 months) OAC in the prevention of VTEs after CVT.
Method: Participating centres are asked whether they have preference for any of the policy treatment options. Centres with no preference are randomly allocated for one of the two options. Adult subjects with confirmed CVT are treated according to the approach allocated to their centre as soon as their acute clinical situation is stable and not more than 1 month after CVT diagnosis. Those with conditions judged by the investigator to be absolute indication for prolonged OAC are excluded. Follow-up is performed at 6, 12, 18 (telephone-interview) and 24 months. Primary efficacy outcome is any symptomatic and confirmed VTE (recurrent CVT or other systemic VTE) or death associated with venous thromboembolism. Primary safety endpoints include bleeding events (major/minor and according to the site), and death from any cause.
Results: At present, a total of 386 subjects with CVT have been included from 29 active centres.
Conclusion: The results of this study will provide crucial evidence regarding optimal duration of OAC after CVT.
LB30-013
3ONGOING TRIALS
POSTURAL STABILITY IN PATIENT AFTER ISCHEMIC STROKE
M. Mierzwa-Molenda1
1Regional Hospital in Kielce, Rehabilitation, Kielce, Poland
Background and Aims: The aim of the study is to compare postural stability between ischemic stroke patients and control group.
Method: A total of 13 ischemic stroke patients and 15 age-matched patients without stroke incident as control group were recruited in this study. All patients were evaluated by the Postural Stability test on stability platform.
Results: There were a significant difference in Global Stability Index (%) in stroke patients compared to control group.
Conclusion: There were significantly worse in parameters of PS test in stroke patients group.
LB33-001
WOMEN AND STROKE
DAWN in full daylight (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention)
T.G. Jovin1, R.G. Nogueira1for the DAWN investigators
1Grady Memorial Hospital, emory University School of Medicine, USA
Background: The efficacy of mechanical thrombectomy for acute stroke due to large vessel occlusion (LVO) initiated beyond 6 hours of time last seen well (TLSW) has not been demonstrated by randomized trials.
Aim: To establish whether subjects considered to have substantial areas of salvageable brain based on age-adjusted clinical core mismatch (CCM) who can undergo thrombectomy with the Trevo device within 6–24 hours from TLSW have better outcomes at 3 months compared to subjects treated with standard medical therapy alone. Age-adjusted CCM was defined by age (≤80 or >80 years), baseline NIHSS (10–20 or ≥21) and core size (0–20 cc’s in subjects older than 80 and, in subjects younger than 80, 0–30 cc’s with NIHSS 10–20 and 31–50 cc with NIHSS ≥ 21).
Method: Prospective, randomized, multicenter, Bayesian adaptive-enrichment, open label trial with blinded endpoint assessment. Subjects were randomized in a 1:1 ratio to receive thrombectomy or medical management alone. Sequential interim analyses allowing adaptation of enrolment criteria or stopping new enrolment for futility or predicted success was planned to occur every 50 randomized patients starting at 150 to a maximum of 500 patients. The primary endpoint was the modified Rankin Scale (mRS) score at 90 days analyzed as a utility weighted score and (due to regulatory considerations) also as a dichotomized variable. The primary safety outcome was stroke-related mortality at 90 days.
Results: Trial enrolment was stopped at the DSMB’s recommendation due to crossing of pre-specified probability thresholds for predicted success. Full results will be provided at the presentation.
LB1000
Official Welcome & Large Clinical Trials
PFO Closure in the Gore REDUCE Clinical Trial: Primary Results
S.E. Kasner1, L. Søndergaard2, J.F. Rhodes3 and L. Thomassen4
1Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
2Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
3Department of Cardiology, Nicklaus Children's Hospital, Miami, FL, USA
4Department of Neurology, Haukeland University Hospital, Bergen, Norway
Background and Aims
The efficacy of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke has been uncertain despite multiple randomized trials completed to date. The Gore REDUCE Clinical Study (REDUCE) aimed to establish superiority of PFO closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke.
Method
REDUCE was a randomized, controlled, open-label trial that randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus PFO closure (with Gore® Helex® Septal Occluder or Gore® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. A standardized approach to antiplatelet therapy was defined by protocol. Subjects were prospectively followed for at least 2 and up to 5 years. Neuroimaging was required for all subjects at baseline and at 2 years or study exit.
A blinded Clinical Endpoint Committee (CEC) reviewed and adjudicated all suspected stroke, TIA, and death events. A blinded MRI core laboratory compared baseline and 2-year MRI to determine the presence of new silent brain infarction.
The two co-primary endpoints for the study were freedom from recurrent clinical ischemic stroke through at least 2 years after randomization and incidence of new brain infarct (defined as the composite of clinical ischemic stroke and silent brain infarct) through 2 years. The primary analyses were performed on the intention-to-treat population using an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, with adjustment for testing multiplicity.
The CEC completed adjudication of all potential clinical endpoints on 17 April 2017 and the primary analysis was performed on 24 April 2017. The primary endpoint results of REDUCE will be presented
