Abstract Body: Background and Aims: The potential benefit of intra-arterial alteplase after successful endovascular reperfusion for improving functional outcomes in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) remains unclear. The PEARL trial aims to provide high-level evidence for this intervention.

Methods: PEARL is an investigator-initiated, multicenter, prospective, randomized controlled, open-label, blinded endpoint (PROBE) trial. AIS patients presenting with anterior-circulation LVO and NIHSS scores 6-25 within 24 hours from stroke onset and achieving stable eTICI scores of 2b50-3 after mechanical thrombectomy (MT) were randomly assigned (1:1) to receive either intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) or standard medical treatment alone. Randomization was stratified by center and the use of intravenous thrombolysis. The primary outcome was the proportion of patients achieving a 90-day modified Rankin Scale of 0-1. The trial was designed with an expectation of a 16% difference (56.4% vs 40.4%) in the proportion of excellent outcome (mRS 0-1) at 90 days with a planned sample size of 324 subjects.

Results: The PEARL trial received approval from the Ethics Committee of Sun Yat-sen Memorial Hospital and all participating centers, with registration at ClinicalTrials.gov (NCT05856851). Between August 1, 2023, and October 16, 2024, a total of 324 participants were successfully randomized across 28 stroke centers in China. The final study results will be presented at the ISC-2025.

Conclusions: The PEARL trial is expected to provide robust evidence on the efficacy of intra-arterial alteplase following successful endovascular reperfusion to improve outcomes among LVO patients in China.