Four-Factor Prothrombin Complex Superior to Plasma for Rapid VKA Reversal

In results from a Phase 3b trial in 168 patients needing urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA) therapy, 78 patients (90 percent) treated with CSL Behring’s four-factor prothrombin complex concentrate (Kcentra; 4F-PCC) achieved effective hemostasis, compared with 61 patients (75 percent) treated with plasma. 4F-PCC demonstrated both noninferiority and superiority compared with plasma for this primary endpoint.

A co-primary endpoint — rapid reduction of the International Normalized Ratio (INR) to ≤1.3 at 0.5 hours after the end of infusion — was achieved in 48 patients (55 percent) treated with 4FPCC vs. eight patients (10 percent) treated with plasma. The safety profile of 4F-PCC was generally similar to plasma, with 56 percent and 60 percent experiencing adverse events, respectively. While thromboembolic adverse events (7 percent vs. 8 percent) and late bleeding events (3 percent vs. 5 percent) were also similar, just three patients (3 percent) receiving 4F-PCC experienced fluid overload or similar cardiac events, compared with 11 patients (13 percent) of patients receiving plasma therapy.

The investigators concluded that 4F-PCC is noninferior and superior to plasma for rapid INR reversal and effective hemostasis in patients needing VKA reversal for urgent surgical or invasive procedures.