CAPTIVA is a two-stage Phase III, double-blind, randomized trial conducted in subjects age 30 and older with a symptomatic infarct attributed to 70-99% stenosis 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). The study will enroll 1,683 subjects at over 100 StrokeNet and non-StrokeNet sites over a 4-year period. Subjects with will be randomized 1:1:1 to one year of treatment with:
- ticagrelor (180 mg loading dose, then 90 mg twice daily) + aspirin (81 mg daily), or
- low dose rivaroxaban (2.5 mg twice daily) + aspirin (81 mg daily), or
- clopidogrel (600 mg loading dose, then 75 mg daily) + aspirin (81 mg daily)
All subjects will receive intensive risk factor management and lifestyle coaching similar to that in the SAMMPRIS and CREST-2 trials.
All subjects will be evaluated at 1 month, 4 months, 8 months, and 1 year after randomization when they will have their blood pressure measured, risk factors optimized, and will be assessed for study endpoints.
The main intent of CAPTIVA is to establish that at least one of the two novel therapies being evaluated is more effective than the current standard. CAPTIVA is not designed or powered to answer which of the two novel arms is more effective – that would require a much larger sample size. Nevertheless, CAPTIVA will provide important safety and efficacy data on both novel therapies.
Safety Aim: To identify an excess of parenchymal intracerebral hemorrhage (ICH) or non-ICH major hemorrhage in the rivaroxaban or ticagrelor arms of the trial that could lead to an early termination of one or both of those arms. This aim will be evaluated in a prespecified safety analysis marking the conclusion of the first stage of the trial.
Efficacy Aim: To determine if the experimental arm(s) (rivaroxaban or ticagrelor or both) that progress to the second stage are superior to the clopidogrel arm for lowering the 1-year rate of the primary efficacy endpoint (ischemic stroke, ICH, or vascular death) in subjects with 70-99% symptomatic Intracranial Atherosclerotic Stenosis (sICAS).
Exploratory Aim: To estimate the impact of CYP2C19 loss-of-function 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.