4F-PCC was noninferior to plasma for 24-hour hemostatic efficacy (72.4% vs 65.4%; difference 7.1%, 95% CI -5.8 to 19.9) and superior for rapid INR reduction (62.2% vs 9.6%).
RCT (n=202)
open-label
randomized
Yes
Does 4F-PCC improve hemostatic efficacy and INR correction compared to plasma in patients on vitamin K antagonists presenting with major bleeding?
4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, demonstrating noninferior hemostatic efficacy and superior rapid INR reduction.
Effect estimate: difference 7.1% (95% CI -5.8 to 19.9)
Absolute Event Rate: 72.4% vs 65.4%
BACKGROUND: Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal. METHODS AND RESULTS: In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8-20.0) for the 4F-PCC group and 3.60 (1.9-38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% 95% confidence interval, -5.8 to 19.9). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% 95% confidence interval, 39.4 to 65.9). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event. CONCLUSIONS: 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708435.
Sarode et al. (Sat,) conducted a rct in Major bleeding while taking vitamin K antagonists (n=202). 4-factor prothrombin complex concentrate (4F-PCC) vs. plasma was evaluated on 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion (difference 7.1%, 95% CI -5.8 to 19.9). 4F-PCC was noninferior to plasma for 24-hour hemostatic efficacy (72.4% vs 65.4%; difference 7.1%, 95% CI -5.8 to 19.9) and superior for rapid INR reduction (62.2% vs 9.6%).