Reteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE): rationale and design of a multicentre, prospective, randomised, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial

Abstract

Background and purposeReteplase is the third generation of alternative thrombolytic agent. We hypothesis that reteplase will be non-inferior to alteplase in achieving excellent functional outcome at 90 days among eligible patients with acute ischaemic stroke.Methods and designReteplase versus alteplase for acute ischaemic stroke within 4.5 hours (RAISE) trial is a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled phase 3 non-inferiority trial. A total of 1412 eligible patients will be randomly assigned to receive either reteplase at a dose of 18 mg+ 18 mg or alteplase 0.9 mg/kg at a ratio of 1:1. An independent data monitoring committee will review the trail’s progress and safety data.Study outcomesThe primary efficacy outcome of this study is proportion of individuals attaining an excellent functional outcome, defined as modified Rankin Scale (mRS) 0–1 at 90 days. The secondary efficacy outcomes encompass favourable functional outcome defined as mRS 0–2, major neurological improvement on the National Institutes of Health Stroke Scale, ordinal distribution of mRS and Barthel Index score of at least 95 points at 90 days. The primary safety outcomes are symptomatic intracranial haemorrhage at 36 hours within 90 days.DiscussionThe RAISE trial will provide crucial insights into the selection of thrombolytic agents for stroke thrombolysis.Trial registration numberNCT05295173.