NIH Halts Low-Dose Rivaroxaban Arm in CAPTIVA Stroke Study Due to Safety and Futility Concerns

The National Institutes of Health (NIH) has announced the discontinuation of the low-dose rivaroxaban treatment arm within the Comparison of Anti-coagulation and Anti-platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) study. This critical decision followed a recommendation from an independent Data Safety and Monitoring Board (DSMB) due to an increase in safety events and strong evidence that the treatment was unlikely to provide benefit.

Discontinuation of Rivaroxaban Arm

The NIH's National Institute of Neurological Disorders and Stroke (NINDS), the trial's funder, accepted the DSMB's recommendation after a thorough review of study data.

Reasons cited for the discontinuation included an observed increase in safety events among participants receiving rivaroxaban and evidence of futility.

Futility is a pre-specified stopping condition indicating that the treatment was unlikely to offer benefit to study participants.

About Rivaroxaban

Rivaroxaban is an anticoagulant medication approved by the U.S. Food and Drug Administration (FDA) for the treatment and prevention of blood clots.

Following the decision, all active study sites with participants randomized to the discontinued rivaroxaban arm have received instructions for drug cessation. Affected participants, including those actively receiving the drug and those who completed their evaluation in this arm, will be contacted by their respective treatment sites.

Overview of the CAPTIVA Study

The CAPTIVA study is structured as a large, two-stage, double-blind randomized trial. Its primary aim is to determine if either of two investigational treatments is more effective than the current standard of care in preventing recurrent strokes.

Participants in the study are individuals aged 30 and older who have experienced a stroke resulting from a 70-99% narrowing (stenosis) of a major intracranial artery. The trial is part of NIH's StrokeNet and is designed to enroll and evaluate up to 1,683 volunteers across more than 100 sites over a four-year period.

Treatment Regimens

Initially, participants were randomized 1:1:1 to one year of treatment with one of the following regimens, in addition to intensive risk factor management and lifestyle coaching:

• Ticagrelor (180 mg loading dose, then 90 mg twice daily) plus aspirin (81 mg daily), which serves as a comparison to the current standard of treatment.
• Low-dose rivaroxaban (2.5 mg twice daily) plus aspirin (81 mg daily), which has been discontinued.
• Clopidogrel (600 mg loading dose, then 75 mg daily) plus aspirin (81 mg daily).

Evaluations for study outcomes, including blood pressure checks and risk factor optimization, are conducted at one month, four months, eight months, and one year post-randomization. The study's design focuses on assessing whether new treatments are superior to existing care, rather than directly comparing the two novel therapies against each other.

The CAPTIVA Study and NIH’s StrokeNet are funded by NIH’s National Institute of Neurological Disorders and Stroke (NINDS).