Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study protocol and rationale

Abstract

Rationale:

The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.

Aims:

This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.

Sample size:

To detect an estimated 15% difference in the primary outcome between the two groups, a total of 376 patients will be enrolled. This sample size allows for 80% power and a 5% significance level, with an interim analysis planned after half of the sample (188 patients) has completed a 90-day follow-up.

Methods and design:

The Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP) trial is a multicenter, prospective, randomized clinical trial using an open-label treatment design with blinded endpoint assessment (PROBE) conducted in China. Patients with acute basilar artery occlusion will be randomly assigned in a 1:1 ratio to receive either intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or standard care following successful thrombectomy (defined as expanded thrombolysis in cerebral infarction [eTICI] ⩾ 2b50).

Study outcomes:

The primary outcome is the modified Rankin Scale (mRS) score of 0–2 at 90 days. Key secondary outcomes include changes in eTICI scores after intra-arterial thrombolysis (in the experimental group), mRS 0–3 at 90 days, ordinal shift analysis of mRS at 90 days, early neurological improvement at 48 h, and improvement in National Institutes of Health Stroke Scale (NIHSS) scores at 48 h and 7 days or discharge. Safety outcomes include symptomatic intracranial hemorrhage (sICH) rates at 48 h, 90-day mortality, non-intracranial hemorrhagic complications, and non-hemorrhagic serious adverse events.

Discussion:

The IAT-TOP trial will provide crucial evidence regarding the potential benefits of adjunctive intra-arterial alteplase in patients with AIS-LVO in the posterior circulation following successful thrombectomy.

Trial registration:

ClinicalTrials.gov NCT05897554