Safety and Efficacy of Early Aspirin Administration After Intravenous Thrombolysis for Acute Ischemic Stroke (TREND‐IVT): Rationale and Design of a Multicenter, Randomized, Placebo‐Controlled Clinical Trial

Background In acute ischemic stroke, early neurological deterioration following intravenous thrombolysis (IVT) is common and is associated with unfavorable outcomes, necessitating antiplatelet therapy. TREND‐IVT (Trial of Early Aspirin After Intravenous Thrombolysis for Acute Ischemic Stroke) aims to evaluate the safety and efficacy of 300 mg aspirin administered within 3 hours after the initiation of IVT compared with standard antiplatelet therapy for improving functional outcomes in patients with acute ischemic stroke. Methods This multicenter, randomized, placebo‐controlled trial in China recruits patients with acute ischemic stroke receiving IVT (alteplase/tenecteplase) who are not scheduled for endovascular therapy. Participants are randomized in a 1:1 ratio to receive either early aspirin or placebo within 3 hours of initiating IVT, followed by guideline‐recommended standard antiplatelet therapy beginning 24 hours after IVT in both groups. The primary outcome is an excellent functional outcome, defined as a modified Rankin Scale (mRS) score 0 to 1 at 90 days. Secondary outcomes will include mRS score 0 to 1 at 30 days, mRS score 0 to 2 at 90 days, ordinal shift analysis of mRS scores at 90 days, and changes in the National Institutes of Health Stroke Scale scores within 7 days. Safety end points will include symptomatic intracerebral hemorrhage, any intracerebral hemorrhage within 48 hours, systemic bleeding, recurrent stroke, other vascular events, mortality, and other adverse events during the 90‐day follow‐up. A sample size of 1184 participants will provide 80% power to detect an 8% intergroup difference in the primary outcome rate (2‐sided α=0.05). Conclusions The trial will evaluate the safety and efficacy of early antiplatelet therapy with oral aspirin in patients with acute ischemic stroke treated with IVT and may provide a promising strategy for improving the functional outcomes in this patient population. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT06548971.