Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease

Inclusion criteria

• Age ≥ 40 years
• Recent brain ischemia attributed to intracranial atherosclerotic stenosis of 30-99% as evidenced by CT or MR angiography, occurring between 7 to 100 days prior to randomization and consisting of either:

• a high-risk TIA defined as TIA with motor and/or speech involvement or
• an ischemic stroke
• Written informed consent consistent with local regulations governing research in human subjects

Exclusion criteria

• Indication for DAPT for > 90 days on guideline recommendations or investigator ́s judgment; e.g., cardiac stenting.
• Indication for chronic anticoagulation based on guideline recommendations or investigator ́s judgment; e.g. patient with prosthetic mechanical valve, venous thromboembolism, hypercoagulable state
• Atrial fibrillation or a history of atrial fibrillation
• Intracranial arterial occlusion (e.g. 100% stenosis) responsible for the acute brain ischemia
• Intracranial arterial stenosis secondary to causes other than atherosclerosis
• Extracranial carotid artery disease ipsilateral to the qualifying brain ischemia with a plan for carotid revascularization
• Intraluminal thrombus
• Subdural hematoma within 12 months of randomization
• Previous spontaneous hemorrhagic stroke (e.g. intracerebral or subarachnoid hemorrhage)
• Traumatic brain hemorrhage within 1 month of randomization
• Contraindication for MRI scan (e.g. pacemaker incompatible with MRI)
• Advanced kidney disease (recent estimated GFR <30 ml per minute)
• Modified Rankin Scale (mRS) >=4 at entry
• Platelet count less than 100,000/mm3 at enrolment or other bleeding diathesis
• Uncontrollable hypertension with systolic BP/ diastolic BP consistently above180/100mmHg after treatment
• Known hypersensitivity to either ASA or rivaroxaban
• Life expectancy less than 6 months
• Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e., human immunodeficiency virus protease inhibitors and the following azole-antimycotics agents: ketoconazole, itraconazole, voriconazole, or posaconazole, if used systemically
• Female of childbearing potential who are not surgically sterile, or, if sexually active not willing to use adequate contraceptive measures with a failure rate less than 1% per year (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, male partner sterilization) before entry and throughout the study, as well as pregnant or breast-feeding women
• Inability to adhere to study procedures
• Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g., employee or student of the investigational site)
• Previous randomization to this study or participating in a study with an investigational drug or medical device at the time of randomization
• Antiphospholipid antibody syndrome