Tirofiban vs standard antiplatelet therapy in acute branch atheromatous disease-related stroke: a multicenter, randomized, open-label, blinded-endpoint, parallel-group, phase III clinical trial

Background Tirofiban is sometimes used empirically for branch atheromatous disease (BAD)-related stroke, but its benefit in this population remains unclear. This study aimed to assess the efficacy and safety of intravenous tirofiban administered within 48 h of onset in patients with acute BAD-related stroke. Methods This multicentre, randomized, open-label, blinded-endpoint clinical trial enrolled patients with BAD-related stroke within 48 h of onset from 25 hospitals in China between 9 November 2023 and 22 November 2025. Eligible patients were randomly assigned to the tirofiban group (intravenously, 0.4 μg/kg per minute for 30 min, followed by a 0.1 μg/kg per minute for 47.5 h) or standard antiplatelet therapy group (oral aspirin with or without clopidogrel) for 48 h. The primary endpoint was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Safety outcomes included major bleeding within 90 days. This trial was registered on ClinicalTrials.gov (NCT06037889). Findings Among 516 patients randomized, 513 were included in the primary analysis (258 with tirofiban and 255 with standard antiplatelet therapy). An excellent functional outcome was observed in 181 of 258 patients (70.2%) in the tirofiban group and 178 of 255 (69.8%) in the standard antiplatelet therapy group (risk ratio, 1.01 [95% CI, 0.90–1.13]; P=0.93). Major bleeding occurred in 0 of 259 participants in the tirofiban-exposed safety population and 1 of 245 (0.4%) in the standard-antiplatelet-exposed safety population. Interpretation Among patients with acute BAD-related stroke, intravenous tirofiban administered within 48 h of onset without concomitant oral antiplatelet therapy was not superior to standard antiplatelet therapy for achieving an excellent functional outcome at 90 days. These findings should not be extrapolated to substantially earlier treatment or to other tirofiban-based antiplatelet strategies. Funding National High Level Hospital Clinical Research Funding, Capital's Funds for Health Improvement and Research, CAMS Innovation Fund for Medical Sciences (CIFMS), Noncommunicable Chronic Diseases-National Science and Technology Major Project, and China Shijiazhuang Pharmaceutical Company (CSPC) NBP Pharmaceurical Co., Ltd.