Comparison of Anti-Coagulation and Anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA)

• Acute focal symptoms or signs of any duration associated with imaging, pathological or other objective evidence of arterial infarction OR clinical evidence of cerebral, spinal cord or retinal focal arterialischemic injury based on symptoms persisting > 24 hours that occurred within 30 days prior to randomization
• Index stroke in 1 above is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, middle cerebral artery (M1 or M2), vertebral artery (V4), basilar artery, posterior cerebral artery (P1) or anterior cerebral artery (A1)) documented by CTA, MRA or catheter angiography
• Modified Rankin Scale score of ≤ 4
• Ability to swallow pills
• At least 30 years of age, inclusive, at time of consent
• Negative pregnancy test in a female who has had any menses in the last 18 months and has not had surgery that would make her unable to become pregnant
• Subject is willing and able to return for all follow‐up visits required by the protocol
• Subject is available by phone
• Subject understands the purpose and requirements of the study and can make him/herself understood
• Subject has provided informed consent (use of a LAR is not permitted)

Patients meeting any one or more of these exclusion criteria are not eligible:

• Previous treatment of target lesion with a stent, angioplasty or other mechanical device, including mechanical thrombectomy for the qualifying stroke, or plan to perform one of these procedures
• Plan to perform concomitant endarterectomy, angioplasty or stenting of an extracranial vessel tandem to the symptomatic intracranial stenosis
• Intracranial tumor (except meningioma) or any intracranial vascular malformation
• Thrombolytic therapy within 24 hours prior to randomization
• Progressive neurological signs within 24 hours prior to randomization
• History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural)
• Intracranial arterial stenosis due to arterial dissection; MoyaMoya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with CSF pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; postpartum angiopathy; suspected vasospastic process; reversible cerebral vasoconstriction syndrome (RCVS); suspected recanalized embolus
• Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months or left atrial spontaneous echo contrast
• Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel or ticagrelor
• Uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), active peptic ulcer disease, major systemic hemorrhage within 30 days prior to randomization, active bleed or bleeding diathesis, platelets < 100,000, hematocrit < 30, INR > 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, severe liver impairment (AST or ALT > 3 x normal, cirrhosis) or CrCl < 15 mL/min or on dialysis
• Major surgery (including stenting of any vessel; open femoral, aortic or carotid surgery; cardiac surgery) within 30 days prior to randomization or planned within 90 days after randomization
• Any condition other than intracranial arterial stenosis that requires the subject to take any antithrombotic medication other than aspirin (NOTE: exceptions allowed for subcutaneous heparin for deep vein thrombosis [DVT] prophylaxis)
• Dementia or psychiatric problem that prevents the subject from following an outpatient program reliably
• Co‐morbid conditions that may limit survival to less than 12 months
• Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study, or currently breastfeeding (If a subject becomes pregnant during the course of the study, investigational product should be discontinued immediately)
• Current or anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors or CYP3A4 substrates that cannot be stopped for the course of this study
• Enrollment in another study that would conflict with the current study