Supplementary Material for: 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. Individualised 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-endpoint (PROBE) trial evaluating platelet function-guided precision antiplatelet therapy compared with standard aspirin monotherapy in patients with non-cardioembolic ischemic stroke. A total of 1018 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 continue to receive aspirin. The primary outcome is HOPR at 30±5 days post-randomisation. Secondary outcomes include all major ischemic events, any stroke (ischemic or hemorrhagic), health-related quality of life (HRQoL), 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.

Trial registration: The trial is registered at ClinicalTrials.gov (NCT06269432).

引言： 有相当比例的缺血性脑卒中患者在阿司匹林治疗期间会出现治疗中血小板反应性增高（high on-treatment platelet reactivity, HOPR），这会引发“阿司匹林抵抗”，并增加复发性缺血性血管事件的风险。基于血小板功能检测的个体化抗血小板策略或可改善脑卒中预后。

方法： PATH STROKE研究是一项多中心、前瞻性、随机对照、开放标签、终点盲法（PROBE）试验，旨在对比血小板功能指导下的精准抗血小板治疗与标准阿司匹林单药治疗，用于非心源性栓塞性缺血性脑卒中患者。共纳入发病于1~3个月内、每日服用阿司匹林100mg的缺血性脑卒中患者1018例，按1:1比例随机分配至指导治疗组或标准治疗（对照）组。指导治疗组中，确诊为HOPR（最大血小板聚集率≥35%）的患者需逐步调整抗血小板治疗方案，换用氯吡格雷或替格瑞洛；标准治疗组则持续接受阿司匹林治疗。本研究的主要终点为随机化后30±5天时的HOPR水平；次要终点包括所有主要缺血事件、任意类型脑卒中（缺血性或出血性）、健康相关生活质量（health-related quality of life, HRQoL），以及依照出血学术研究联合会（Bleeding Academic Research Consortium, BARC）标准分级的出血事件。

结论： PATH STROKE研究是首个评估血小板功能指导下的精准医疗策略用于缺血性脑卒中二级预防的临床试验。

临床试验注册： 本研究已在ClinicalTrials.gov平台注册（注册号：NCT06269432）。