Introduction
The REG1 Anticoagulation System (Regado Biosciences) is a novel, aptamer-based, factor IXa inhibitor, pegnivacogin. Coupled with the reversible agent, anivamersen, this approach was developed for patients undergoing PCI. The safety and efficacy of REG1 compared with established anticoagulants is unknown.
Material and methods
We conducted a Phase 3, randomized (1:1), open-label, multi-center study comparing REG1 to bivalirudin in patients undergoing PCI. The study was designed to include 13,200 patients. The main exclusion criteria were STEMI within 48 hours, contraindication for anticoagulation or high risk for bleeding, and allergy or intolerance to aspirin or all available ADP/P2Y12 inhibitors. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke or unplanned target lesion revascularization at day 3 after randomization. The primary safety endpoint was a BARC 3 or 5 bleeding at day 3. Safety evaluation was conducted by an Independent Data Safety Monitoring Board. A Clinical Events Committee provided an independent and blinded key endpoints assessment.
Results
The study was terminated early due to an excess of serious allergic reactions in the REG1 arm. Final enrollment was 3232 patients from 325 centers. The 2 treatment groups were well-balanced for baseline characteristics. At 3 days there were no differences in the occurrence of the primary endpoint between REG1 and bivalirudin (6.7% vs. 6.4%; OR: 1.05; 95% CI: 0.80 – 1.39; p = 0.72). REG1 was associated with a numerically higher rate of BARC 3 or 5 bleeding (0.4% vs. 0.1%; OR: 3.49; 95% CI: 0.73 – 16.82; p = 0.09) and a significantly higher rate of BARC 2, 3 or 5 bleeding (6.5% vs. 4.1%; OR: 1.65; 95% CI: 1.19 – 2.25; p = 0.002) compared with bivalirudin. Serious allergic events were observed within 24 hours after drug administration in 10/1605 patients who received REG1 (0.6%), including one fatal event and 9 anaphylactic reactions. One patient who received bivalirudin had a serious allergic event (< 0.1%).
Conclusions
REG1 anticoagulation system was associated with similar rates of primary efficacy endpoint at day 3, but higher rates of bleeding and serious allergic events compared with bivalirudin.
