New 4F-PCC Proves Effective in Rapid Reversal of Anticoagulation for Urgent Surgery, Clinical Trial Finds

An investigational 4-factor prothrombin complex concentrate (4F-PCC) is as effective and safe as an FDA-approved 4F-PCC for rapidly reversing vitamin K antagonist (VKA) anticoagulation in patients requiring urgent surgery, according to a study published in JAMA Network Open.

“We conducted the first phase 3 randomized clinical trial (LEX-209; Study of Octaplex, a Four-factor Prothrombin Complex Concentrate [4F-PCC] and Beriplex P/N [Kcentra] for the Reversal of Vitamin K Antagonist [VKA] Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk) comparing the use of two 4F-PCCs among patients taking VKA in need of urgent surgery,” explained Ravi Sarode, MD, Division of Transfusion Medicine and Hemostasis, Department of Pathology, University of Texas Southwestern Medical Center, Department of Internal Medicine (Hematology/Oncology), University of Texas Southwestern Medical Center in Dallas, TX, and coauthors.

The study enrolled 208 adults across multiple countries. Participants were randomly assigned to receive either the investigational or control 4F-PCC. It was conducted from June 7, 2017 through November 8, 2021.

The primary objective of hemostatic noninferiority was met, with effective hemostasis achieved in 94.3% of patients receiving the investigational 4F-PCC compared to 94.2% in the control group. Additionally, both groups showed similar rates of achieving an international normalized ratio (INR) of 1.5 or lower 30 minutes after infusion (78.1% vs 71.8%).

Safety profiles were comparable between the 2 groups, with similar rates of treatment-emergent adverse events (81.9% vs 77.7%). The most common adverse events included procedural pain, postoperative wound complications, asthenia, and anemia. Thrombotic events were rare, with 4 events occurring in 3 patients (2.9%) in the investigational group and none in the control group.

“This randomized clinical trial found that the investigational 4F-PCC was hemostatically noninferior to the control 4F-PCC for rapid VKA reversal in patients needing urgent surgery with considerable bleeding risk; the safety profile of these two 4F-PCCs was similar,” concluded the study authors. “These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal,” they added.

Reference

Sarode R, Goldstein JN, Simonian G, et al. Vitamin K antagonist reversal for urgent surgery using 4-factor prothrombin complex concentrates: A randomized clinical trial. JAMA Netw Open. 2024;7(8):e2424758. doi:10.1001/jamanetworkopen.2024.24758