Bristol-Myers Squibb and Pfizer have discontinued the Phase 3 APPRAISE-2 trial in patients with recent acute coronary syndrome (ACS) treated with apixaban or placebo, in addition to mono or dual-antiplatelet therapy. The study was stopped early based on the recommendation of an independent data monitoring committee because there was clear evidence of a “clinically important increase” in bleeding among patients randomized to apixaban.

The increase in bleeding was not offset by clinically meaningful reductions in ischemic events, according to the companies.

The APPRAISE-2 Trial (Apixaban for Prevention of Acute Ischemic Events-2), one of nine clinical trials evaluating apixaban in patients at risk of ischemic events, was designed to include approximately 10,800 patients with a recent ACS. Patients were randomized to apixaban 5 mg twice daily or placebo. The study was conducted in 40 countries and was coordinated by Duke Clinical Research Institute (DCRI) in Durham, N.C., and Uppsala Clinical Research Center in Sweden.

The companies said they have informed the APPRAISE-2 investigators, ethics review boards and regulatory health authorities of the decision to stop the study. Enrollment will be stopped and patients will be taken off of the study drug. The lead investigators will complete an evaluation of the available data and the results will be made public.

“Our recommendation to discontinue APPRAISE-2 concerns only the population of high-risk ACS patients receiving antiplatelet therapy enrolled in APPRAISE-2,” said Robert A. Harrington, MD, from DCRI, and co-chair of the APPRAISE-2 steering committee. “Recent Phase 3 clinical trials of apixaban have demonstrated promising results in patients with venous thromboembolism and atrial fibrillation.”

Based on the APPRAISE-2 recommendation, the DMC for APPRAISE Japan, a Phase 2 study in ACS patients, also has recommended discontinuation for APPRAISE Japan.