Investigational 4F-PCC Non-Inferior to Control for Vitamin K Antagonist Reversal

An investigational 4-factor prothrombin complex concentrate (4F-PCC) was hemostatically non-inferior to a licensed control 4F-PCC for the rapid reversal of vitamin K antagonists (VKA) in patients needing urgent surgery, according to study findings published online in JAMA Network Open.

“These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal,” wrote corresponding author Ravi Sarode, MD, of the University of Texas Southwestern Medical Center, Dallas, Texas, and study coauthors.

The phase 3 randomized clinical trial (LEX-209; Study of Octaplex, a 4F-PCC and Beriplex P/N for the Reversal of VKA-Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk) spanned 2 dozen hospitals in the United States, Russia, Georgia, Belarus, Ukraine, and Romania. Some 208 adult patients taking VKA and in need of urgent surgery with a substantial bleeding risk were randomized 1:1 to a single infusion of either the investigational or control 4F-PCC. 

Among the 105 patients in the investigational group, the median 4F-PCC dose was 25 IU/kg, infusion time was 12 minutes, and time from infusion to surgery was 1.42 hours. The baseline median international normalized ratio (INR) was 3.05. For the 103 patients in the control group, the median 4F-PCC dose was 25 IU/kg, infusion time was 13 minutes, time from infusion to surgery start was 1.50 hours, and baseline INR was 3.00.

In the intention-to-treat analysis, 94.3% of patients in the investigational group and 94.2% of patients in the control group achieved effective hemostasis, according to the study. Moreover, 78.1% of patients in the investigational group achieved an INR of 1.5 or lower at 30 minutes after infusion compared with 71.8% of patients in the control group.

Thrombotic events occurred in 2.9% of patients in the investigational group and 0% in the control group. Mortality rates were 4.8% in the investigational group and 1.0% in the control group, although all deaths were considered unrelated to 4F-PCCs, researchers reported. In each treatment group, a single patient discontinued due to adverse events, specifically cardiac disorders unrelated to 4F-PCC.

“The safety profile of the investigational 4F-PCC was similar to that of the control 4F-PCC and as expected in patients requiring VKA reversal to prevent excessive bleeding during surgical procedures,” researchers wrote.

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