Ischemic Stroke – CAPTIVA

Name: CAPTIVA (Comparison of Anti-coagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis) 

Contact: Neringa May (CRC, 352-273-6448) Dr. Anna Khanna (PI) 

Enrolling Hours: M-F (daytime) 

Diagnosis: Acute Ischemic Stroke  

Inclusion:  

1. Symptoms or signs of any duration associated with an infarct on brain imaging that occurred within 30 days prior to randomization  
2. Index infarct in 1 above is attributed to 70-99% stenosis (or flow gap on MRA) of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery) documented by CTA, MRA, or catheter angiography.  
3. Modified Rankin Scale score of ≤ 4  
4. Ability to swallow pills  
5. Age 30-80 years, inclusive, at time of consent. 
6. 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 
7. Subject is willing and able to return for all follow-up visits required by the protocol
8. Subject is available by phone  
9. Subject understands the purpose and requirements of the study and can make him/herself understood  
10. Subject has provided informed consent. 

Exclusion: 

1. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform one of these procedures 
2. Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to the symptomatic intracranial stenosis 
3. Intracranial tumor (except meningioma) or any intracranial vascular malformation 
4. Thrombolytic therapy within 24 hours prior to randomization 
5. Progressive neurological signs within 24 hours prior to randomization 
6. History of any intracranial hemorrhage (parenchymal, subarachnoid, subdural, epidural). asymptomatic radiographic microhemorrhages or hemorrhagic conversion of infarction are not exclusions but the latter requires delaying randomization for 2 weeks from onset of qualifying stroke 
7. 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 
8. 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, left atrial spontaneous echo contrast 
9. Known allergy or contraindication to aspirin, rivaroxaban, clopidogrel, or ticagrelor. 
10. 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, uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), severe liver impairment (AST or ALT > 3 x normal, cirrhosis), on dialysis 
11. Major surgery (including open femoral, aortic, or carotid surgery, cardiac) within 30 days prior to randomization or planned within 90 days after randomization 
12. 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 while hospitalized) 
13. Severe neurological deficit that renders the subject incapable of living independently 
14. Dementia or psychiatric problem that prevents the subject from following an outpatient program reliably 
15. Co-morbid conditions that may limit survival to less than 12 months 
16. 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. 
17. 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  
18. Enrollment in another study that would conflict with the current study 
19. Subjects who are known CYP2C19 LOF carriers are not automatically excluded because of the conflicting data on outcomes in previous studies. Study investigators will be required to inform these subjects of these studies and, if these subjects still wish to participate, they may do so understanding that they may get randomized to the clopidogrel arm.