Photo by Cristina Granados
Results of a phase 3 trial indicate that a 4-factor prothrombin complex concentrate (4F-PCC) is more effective than plasma for reversing acquired coagulation factor deficiency induced by vitamin K antagonist therapy in adults who require urgent surgery or an invasive procedure.
4F-PCC induced hemostasis in more patients and reduced international normalized ratios (INRs) more quickly than plasma.
And the rates of adverse events (AEs) were similar in the 2 groups.
“[4F-PCC] is more effective than plasma for INR reduction and periprocedural hemostasis in adults who are taking warfarin and require an urgent procedure,” said Joshua N. Goldstein, MD, PhD, of Massachusetts General Hospital in Boston.
He and his colleagues reported these findings in The Lancet.
The study included 181 patients, but only 168 were evaluable for efficacy. Eighty-seven of these patients received 4F-PCC, and 81 received plasma.
Ninety percent of patients treated with 4F-PCC achieved effective hemostasis, compared to 75% of patients treated with plasma (P=0.0142).
Fifty-five percent of patients who received 4F-PCC achieved rapid INR reduction (to ≤ 1.3 at 30 minutes after the end of infusion), compared to 10% of patients treated with plasma (P<0.0001).
In post-hoc analysis, the median time from the start of infusion to the start of the urgent surgical procedure was shorter in the 4F-PCC group than in the plasma group—3.6 hours and 8.5 hours, respectively (P=0.0098).
Eighty-eight patients in each group were evaluable for safety. And the incidence of AEs was similar in the 4F-PCC and plasma groups, at 56% and 60%, respectively.
Treatment-related AEs occurred in 9% of 4F-PCC-treated patients and 17% of plasma-treated patients. In both groups, 3% of these AEs were serious.
The rate of death at day 45 was 3% in the 4F-PCC group and 9% in the plasma group. The rates of thromboembolic AEs were 7% and 8%, respectively.
The rates of fluid overload or similar cardiac events were 3% and 13%, respectively. And the rates of bleeding after the primary outcome assessment were 3% and 5%, respectively.
This study was funded by CSL Behring, makers of 4F-PCC, which is marketed as Kcentra, Beriplex, or Confidex.
