PB0559 - LEX-210: a phase 3, randomized, double-blinded study of four-factor prothrombin complex concentrate in patients with acute major bleeding on direct oral anticoagulant therapy with factor Xa inhibitors

Background: Major bleeding associated with direct oral anticoagulant therapy with Factor Xa Inhibitors (FXaI) may be controlled using hemostatic agents such as prothrombin complex concentrates (PCCs). The efficacy/safety of PCCs for use to manage FXaI-related bleeding requires further investigation.

Aims: To demonstrate the hemostatic efficacy/safety of four-factor PCC (4F-PCC; Octaplex®, Octapharma) in adults with FXaI-related major bleeding.

Methods: LEX-210 (NCT04867837) is a Phase 3, multicenter, prospective, randomized, double-blinded, group-sequential, parallel-group, adaptive design study (sponsor: Octapharma). Patients (≥18 years) with acute major bleeding and FXaI activity equivalent to ≥100 ng/mL are eligible. Exclusion criteria include bleeding that is immediately life-threatening and acute trauma for which FXaI reversal alone would not be expected to control bleeding. Approval from independent ethics committees will be sought prior to study start. Prior written informed consent will be obtained from each patient or the patient’s legally authorized representative. Approximately 200 patients will be enrolled and randomized 1:1 to receive 50 IU/kg or 15 IU/kg 4F-PCC, to demonstrate superior hemostatic efficacy of the higher dose for emergency reversal of FXaI related major bleeding. The primary endpoint is the proportion of patients with effective (excellent/good) or non-effective (poor/none) hemostasis within 24 h of 4F-PCC, as determined by an independent adjudication committee consistent with predefined criteria based on Sarode et al. (Table 1) [1]. Secondary endpoints include change in endogenous thrombin potential (baseline to 1 h after PCC), 30-day rates of thromboembolic events and all cause mortality, adverse events, vital signs, and laboratory parameters.

Results: LEX-210 launched in Q4 2021 and will be performed across ~60 sites in North America and Europe. Completion is anticipated Q1 2024.

Conclusion(s): Results could confirm the hemostatic efficacy/safety of 4F-PCC in the management of FXaI-related major bleeding, potentially offering an alternative treatment for these patients.

References:
1. Sarode R et al. Circulation 2013;128:1234-43.