ABSTRACT
STUDY OBJECTIVE: This study compares the safety and efficacy of a fixed dose of 4-factor prothrombin complex concentrate (4FPCC) to the FDA-approved variable dosing for reversal of warfarin-induced anticoagulation. METHODS: This was a single-center, prospective, open-label, randomized controlled trial with subjects randomized to 4FPCC at a fixed dose of 1500 IU or the FDA-approved variable dosing regimen. The primary efficacy outcome (reversal success) was defined as a post-intervention international normalized ratio (INR) of less than or equal to 1.5. Given that 4FPCC is the standard of care for reversal of warfarin-induced anticoagulation an active-controlled approach was employed with the two dosing regimens compared based on efficacy, cost, and safety outcomes. RESULTS: 71 subjects (34 in the fixed dose group and 37 in the variable dose group) completed the study. There were no significant differences in age, gender, weight, initial INR, or indication for 4FPCC administration between the two treatment groups. Reversal success in the fixed-dose group was 61.8%, while in the variable dose group reversal success was 89.2%. Reversal success in the fixed-dose group was significantly lower than the rate of reversal success in the variable dose group (27.4% lower, p = 0.011). CONCLUSION: The results of this study provide evidence that fixed dosing results in lower reversal success rates as compared to variable dosing of 4FPCC for warfarin-induced anticoagulation.
