Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding A Randomized, Plasma-Controlled, Phase IIIb Study
By R. Sarode, T. Milling, M. Refaai, A. Mangione, A. Schneider, B. Durn, J. Goldstein. Circulation, 2013
726 citations recorded by the source corpus.
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.
Subfields: Cardiology and Cardiovascular Medicine, Neurology, Nutrition and Dietetics
View Paper: https://www.semanticscholar.org/paper/7653664710b44080bade2fb4e500159e660697a8
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cardiology and Cardiovascular Medicine
In Neurology
Citations in the corpus
- Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors (2019, neutral): “Restart of oral anticoagulation‖ 100 (28) 31 (9) 37 (11) 32 (9)”
- The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition (2016, methodology): “16 The use of PCC has been shown to be superior to FFP in the rapid reversal of vitamin K 17 antagonists [576-578] with evidence of less haematoma formation in those with head injury 18 [579, 580].”
- Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage (2016, background): “This study compared rates of major bleeding, adverse events, and 3-month functional outcomes (modified Rankin score) among patients who received either FFP alone, 3-factor PCC alone (Bebulin 50 IU/kg IV), or the combination of PCC and FFP [59].”