Oral Abstract
Hematology and Coagulation - Disorders
Sylvia Werner
Senior Director, CRD Hematology
Octapharma, USA Inc., Paramus, NJ, USA
Disclosure information not submitted.
Prothrombin complex concentrates (PCCs) are increasingly used in surgical patients to manage bleeding by enhancing thrombin generation and supporting clot initiation/formation. Elevated international normalized ratio (INR) >1.5 increases postoperative bleeding risk in patients receiving vitamin K antagonists (VKAs) or those with coagulopathy following major surgeries, including cardiopulmonary bypass (CPB). The LEX-209 and LEX-211 Phase 3 randomized controlled trials assessed the efficacy and safety of investigational PCC (Octaplex/Balfaxar) in patients undergoing urgent VKA reversal or cardiac surgery with elevated INR.
Study
Design/Methods:
LEX-209 (NCT02740335) was a double-blind, non-inferiority trial comparing investigational vs. control PCC (Beriplex/Kcentra) in adults (≥18 years) with INR ≥2.0 receiving VKAs prior to urgent surgery. LEX-211 (FARES-II; NCT05523297) was an unblinded, non-inferiority trial comparing investigational PCC vs. frozen plasma (FP) in adults with INR >1.5 following CPB during cardiac surgery. Primary endpoints were hemostatic efficacy (LEX-209) and need for additional hemostatic intervention from 60 min to 24 hours after intervention initiation (LEX-211). Secondary endpoints included INR correction and safety.
Results/Findings:
Overall, 318 patients were treated with investigational PCC (LEX-209: n=105; LEX-211: n=213). Patient baseline characteristics were well balanced between groups in both studies. Table 1 summarizes investigational PCC dosing and infusion timings. In LEX-209, investigational PCC was non-inferior to control PCC, with effective hemostasis achieved postoperatively in 94.3% vs. 94.2% of patients, respectively. INR correction to ≤1.5 at 30 min post-infusion was achieved in 78.1% in the investigational group vs. 71.8% in the control group (proportion difference 0.06; 95% CI, −0.06, 0.18). In LEX-211, investigational PCC was superior to FP in achieving effective hemostasis (p< 0.001) and led to a greater change in INR from within 30 min before to 60 min after investigational medicinal product start (mean decrease of 33.9% vs. 24.9%; least-squares mean −0.15; 95% CI, −0.26, −0.04; p=0.008). Safety profiles were similar between investigational and control PCC groups in LEX-209, while fewer severe treatment-emergent adverse events, including acute kidney injury, were observed for PCC over FP in LEX-211.
Conclusions:
PCC administration demonstrated rapid INR correction in VKA-associated coagulopathy vs. control PCC and significantly greater INR reduction following CPB-associated coagulopathy vs. FP. The investigational PCC was efficacious and well-tolerated, with potential safety benefits over FP, supporting its use in the surgical management of bleeding.