Abstract
INTRODUCTION: Intracranial atherosclerotic disease (ICAD), prevalent in over 65% of Asian populations, is a major cause of global cerebrovascular morbidity and mortality through cerebral hypoperfusion. Despite guideline-directed medical therapy, recurrent ischaemic events remain common due to inadequate collateral circulation. Previous randomised controlled trials (ie, International Extracranial-Intracranial Bypass Study, carotid occlusion surgery study, carotid and middle cerebral artery occlusion surgery study) demonstrated high perioperative risks of extracranial-to-intracranial bypass surgery, while recent single-arm studies suggest that indirect cerebral revascularisation may improve cerebral perfusion with enhanced safety. METHODS AND ANALYSIS: This is a multicentre, randomised, open-label trial designed to enrol 378 participants (189 per group) with symptomatic ICAD (≥70% stenosis/occlusion, American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Score 0-2). Participants will be allocated using minimisation randomisation via an interactive web response system to receive multimodal indirect revascularisation plus intensive medical therapy or intensive medical therapy alone. The primary endpoints are the composite of stroke or death within 30 days and ipsilateral ischaemic stroke within 24 months. Secondary outcomes include transient ischaemic attack reduction, neurological function preservation (modified Rankin Scale), and cerebral perfusion improvements assessed by CT perfusion and MRI. ETHICS AND DISSEMINATION: The study protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (approval number: 2024 Review (2588)). Written informed consent will be obtained from all participants prior to enrolment. The study results will be disseminated through peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2500099882).