Protocol for a Randomized Controlled Trial of Platelet Aggregation Function Guiding Precise Antiplatelet Therapy for Ischemic Stroke: Rationale and Design of the PATH STROKE Study

INTRODUCTION: A significant proportion of patients with ischemic stroke exhibit high on-treatment platelet reactivity (HOPR) on aspirin therapy, which contributes to "aspirin resistance" and an increased risk of recurrent ischemic vascular events. Individualized antiplatelet strategies based upon platelet function testing may improve stroke outcomes. METHOD: The PATH STROKE study is a multicenter, prospective, randomized, controlled, open-label, blinded outcome-assessed (PROBE) trial evaluating platelet function-guided precision antiplatelet therapy compared with standard aspirin monotherapy in patients with non-cardioembolic ischemic stroke. A total of 1,018 patients with a ischemic within the past 1-3 months and receiving aspirin 100 mg daily are eligible to be randomized 1:1 to guided therapy or standard care (control). In the guided group, patients identified with HOPR (maximum aggregation rate ≥35%) undergo stepwise adjustment of antiplatelet therapy switch to clopidogrel or ticagrelor. The standard care group continues to receive aspirin. The primary outcome is HOPR at 30 ± 5 days post-randomization. Secondary outcomes include all major ischemic events, any stroke (ischemic or hemorrhagic), health-related quality of life, and bleeding classified according to the Bleeding Academic Research Consortium (BARC) criteria. CONCLUSION: PATH STROKE is the first clinical trial to evaluate a platelet function-guided, precision medicine, strategy for secondary prevention in ischemic stroke.