VPB0492 - LEX-211 (FARES-II): a phase 3, prospective, active-control randomised study of four-factor prothrombin complex concentrate versus frozen plasma in bleeding adult cardiac surgery patients

Background: Cardiac surgery is often complicated by coagulopathic bleeding, leading to transfusion and poor outcomes. Prothrombin complex concentrate (PCC) and frozen plasma (FP) are used for coagulation factor replacement during surgery.

Aims: To demonstrate that four-factor PCC (4F-PCC, Octaplex®, Octapharma) is clinically non-inferior to FP in terms of haemostatic effectiveness, as measured by the need for post-therapy haemostatic interventions.

Methods: LEX-211 (sponsor: Octapharma) will include patients (≥18 years) undergoing cardiac surgery with cardiopulmonary bypass (CPB) who require coagulation factor replacement due to post-CPB bleeding and known/suspected coagulation factor deficiency. Exclusion criteria include heart transplant, insertion/removal of ventricular assist devices, high probability of death within 24 h, severe right heart failure, heparin contraindications, thromboembolic event (TEE) within 3 months and IgA deficiency. Approximately 500 patients will be randomised to PCC (20–25 IU/kg) or FP (10–15 mL/kg) (Figure 1). The primary endpoint is haemostatic response to PCC vs. FP, rated ‘effective’ if no further haemostatic intervention (systemic haemostatic agents, including second dose of study drug, or surgical re-opening for bleeding) is required 60 min–24 h after initiation of first dose. Secondary endpoints include global haemostatic response (60 min–24 h), bleeding (24 h), blood product/coagulation factor usage (24 h, 7 d), surgical re-exploration (24 h) and coagulation parameters (~1 h post-treatment). Safety endpoints include serious treatment-emergent adverse events (e.g., TEE, major adverse cardiac events), mechanical ventilation, ICU stay, hospitalisation and mortality (30 d).

Results: LEX-211 is planned to start in Q2 2022. An unblinded interim analysis (100 evaluable patients/group) will test sample size assumptions and re-estimate if necessary. Completion is expected Q1 2024.

Conclusion(s): The results of this study will inform clinical practice for bleeding cardiac surgery patients requiring coagulation factor replacement, potentially reducing blood product usage, and improving outcomes.