Randomized trial compares intra-arterial alteplase with standard treatment for stroke outcomes, highlighting efficacy in LVO cases.
Background and aims The long-term functional benefit of intra-arterial alteplase following successful endovascular reperfusion in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) remains uncertain. This study compared adjunct intra-arterial alteplase with standard medical treatment alone after mechanical thrombectomy (MT) achieving stable eTICI 2b50–3 reperfusion. Methods PEARL is an investigator-initiated, multicenter, prospective, randomized controlled PROBE trial. AIS patients with anterior-circulation LVO, NIHSS 6–25, within 24 hours of onset, and stable eTICI 2b50–3 after MT were randomized 1:1 to intra-arterial alteplase (0.225 mg/kg; maximum 20 mg) or standard medical treatment. The primary outcome was the distribution of modified Rankin Scale (mRS) scores at 1 year, analyzed using an assumption-free ordinal approach (Wilcoxon–Mann–Whitney test) to derive a generalized odds ratio. Secondary outcomes included treated-artery stroke recurrence and all-cause mortality within 1 year, assessed using Cox proportional hazards models. Results The trial was approved by ethics committees at Sun Yat-sen Memorial Hospital and participating centers and registered at ClinicalTrials.gov (NCT05856851). Between August 2023 and October 2024, 324 patients were enrolled across 28 stroke centers in China. One-year follow-up has been completed in a proportion of participants, with final results to be presented at ESOC 2026. Conclusions The PEARL 1-year outcomes will provide robust evidence on the long-term efficacy of intra-arterial alteplase after successful MT in patients with LVO. Conflict of interest
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