Abstract Body: Background: The usual treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual antithrombotic treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin. Methods: CAPTIVA is an ongoing, prospective, double-blinded, 3-arm clinical trial at over 100 sites in the USA and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with 1) ticagrelor (180 mg loading dose, then 90mg twice daily), 2) low dose rivaroxaban (2.5mg twice daily), or 3) clopidogrel (600mg loading dose, then 75 mg daily). All subjects receive aspirin (81mg daily), intensive risk factor management, and will undergo blinded CYP2C19 genotype analysis. The primary goal of the trial is to determine whether rivaroxaban or ticagrelor or both are superior to clopidogrel for lowering the primary endpoint (ischemic stroke, intracerebral hemorrhage (ICH), or vascular death) within 12 months. An exploratory aim is to estimate the impact of CYP2C19 loss-of-function (LoF) carrier status on any benefit that the ticagrelor or low dose rivaroxaban arms may have in lowering the primary endpoint compared with the clopidogrel arm. A prespecified interim safety analysis will be conducted when the first 450 randomized subjects have been followed for 12 months to evaluate the risk of major hemorrhage in the rivaroxaban and ticagrelor arms. Results: Enrollment began in August 2022 and, as of June 26, 2024, the 450th subject was randomized into the study. As of October 29, 2024, 541 subjects have been randomized. At the time of presentation at the International Stroke Conference (ISC) 2025, further updates will be given. Conclusion: CAPTIVA is evaluating two alternative dual antithrombotic therapies to clopidogrel and aspirin to maximize the chance of establishing more effective antithrombotic therapy for symptomatic ICAS, one of the most common and high-risk cerebrovascular diseases worldwide.