Chemical Optimization of Cerebral Embolectomy 2 (CHOICE 2) trial: study protocol.

RATIONALE: The potential value of rescue intra-arterial thrombolysis in patients with large vessel occlusion (LVO) stroke treated with mechanical thrombectomy (MT) remains to be validated in randomised trials.

AIM: The Chemical Optimization of Cerebral Embolectomy 2 (CHOICE 2) trial is designed to confirm whether adjunctive intra-arterial alteplase, administered after successful MT, improves clinical outcomes in patients with LVO stroke.

SAMPLE SIZE ESTIMATES: A total of 440 patients (220 per group) randomised in a 1:1 ratio to receive intra-arterial thrombolysis or not intra-arterial thrombolysis provides 80% statistical power to detect a 14% absolute benefit in the primary endpoint (the proportion of patients achieving modified Rankin Scale (mRS) 0-1 at 90 days), assuming a rate of 40% in the control group, a 5% two-sided type I error. The sample size also provides >95% power for detecting an 18% absolute benefit in secondary imaging endpoints, assuming a 58% rate in the control group.

METHODS AND

DESIGN

Multicentre, randomised, open, blinded end-point assessment phase III trial. Eligible patients are adults (≥18 years) with symptomatic LVO who undergo MT with successful or complete reperfusion at end of the procedure. Patients in the intervention group will receive a 15 min intra-arterial infusion of alteplase (1.0 mg/mL, maximum dose 20 mg).

STUDY OUTCOMES: The primary outcome is the proportion of patients achieving excellent functional outcome (mRS 0-1) at 90 days. Key secondary outcomes are the presence of hypoperfusion on brain CT perfusion at 36±24 hours post randomisation, infarct expansion, Barthel Index and quality of life. Mortality and symptomatic intracerebral haemorrhage will also be evaluated.

DISCUSSION: This trial will provide evidence whether rescue intra-arterial thrombolysis improves clinical outcome in patients with LVO stroke who achieve successful or complete angiographic reperfusion following MT.