(486) Efficacy and Safety of High-Dose Four-Factor Prothrombin Complex Concentrate: LEX-209 Subanalysis

Introduction: The LEX-209 Phase 3 randomized controlled trial of investigational four-factor prothrombin complex concentrate (4F-PCC; Octaplex®/Balfaxar®, Octapharma) demonstrated hemostatic non-inferiority to the FDA-approved control 4F-PCC (Beriplex®/Kcentra®, CSL Behring) in rapid vitamin K antagonist (VKA) reversal before urgent surgery (p < 0.001). The aim of this sub-analysis was to assess the hemostatic efficacy and safety of 4F-PCC in patients from LEX-209 with an international normalized ratio (INR) >6, i.e., those receiving a high 4F-PCC dose.

Methods: LEX-209 (NCT02740335), conducted across 24 United States and European hospitals, included 208 patients aged ≥18 years on VKA therapy with INR ≥2.0 and a significant bleeding risk (≥50 mL expected blood loss). Randomized patients (1:1) received a single intravenous 4F-PCC infusion at a dose of 25, 35, or 50 international units (IU) of factor IX/kg for baseline INR 2– < 4, 4–6, or >6, respectively. The primary endpoint, hemostatic non-inferiority, was assessed by a blinded Independent Endpoint Adjudication Board using a surgeon-assessed objective scale. Further endpoints included INR correction and safety.

Results: A total of 23 patients (15 female and 8 male), with baseline INR >6 (mean±SD, 9.1±3.2), were included in this analysis. Median (range) age was 72 (44–90) years and weight 70 (50–115) kg. The mean±SD dose of 4F-PCC administered was similar in investigational (n=15) and control (n=8) 4F-PCC groups (49.7±1.2 IU and 49.2±2.3 IU of factor IX/kg, respectively). Effective hemostasis was achieved in 100.0% of patients in both groups. INR ≤1.5 at 30 min post-infusion was achieved by all except one of the patients on investigational 4F-PCC (proportion difference -0.067; 95% confidence interval -0.247, 0.114). No drug-related treatment-emergent adverse events or thrombotic events were reported in either group.

Conclusions: Investigational 4F-PCC, administered at the maximum permitted dose, appeared to be safe and effective for rapid VKA reversal in urgent surgery patients with significant bleeding risk. These findings further support the use of high-dose 4F-PCC for surgical patients needing rapid VKA reversal.