Efficacy and Safety of 4F-PCC (4-Factor Prothrombin Complex Concentrate) in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass (CPB)

A Phase 3, Multicenter, Randomized, Open-label, Controlled Study to Investigate the Efficacy and Safety of 4-Factor Prothrombin Complex Concentrate in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass

This is a phase 3, multicenter, randomized, open-label, parallel-group, controlled study to assess the efficacy and safety of BE1116 compared with fresh frozen plasma (FFP) in adult participants undergoing complex cardiovascular surgery with CPB. The primary purpose of the study is to compare the efficacy of BE1116 and FFP in correcting coagulation factor deficiencies in bleeding participants undergoing complex cardiovascular surgery with CPB.

Inclusion Criteria:

• Adult greater than or equal to (≥) 18 years and has provided written informed consent.
• Undergoing elective complex cardiovascular surgery requiring CPB, including procedures of the thoracic aorta (with or without additional cardiac interventions), aortic valve replacement + coronary artery bypass graft (CABG), complex valve surgeries, mitral valve repair + CABG, and mitral valve replacement + CABG and reoperative CABG. Reoperative procedures are permitted. Excluded surgeries are as follows: heart transplantation, insertion or removal of ventricular assist devices (except for intra-aortic balloon pumps), and acute repair of thoracoabdominal aneurysms.
• Coagulation factor replacement (ie, 4F-PCC or FFP) is ordered in the operating room for the management of bleeding, in accordance with accepted clinical standards. The following criteria must be met:
• INR ≥ 1.6 (point-of-care INR testing by Hemochron ≥ 5 to 10 minutes after protamine infusion for heparin reversal). If a participant needs a second dose of protamine, a new INR measurement should be performed to confirm eligibility.
• Significant microvascular hemorrhage (ie, not due to surgical complications), as defined by a BSS score of ≥ 2.

Exclusion Criteria:

• Administration of any systemic hemostatic therapy, such as cryoprecipitate, platelets, FFP, PCC (eg, 4-factor / 3-factor PCC [4F-PCC / 3F-PCC]), Factor VIII (FVIII) inhibitor bypassing activity (FEIBA), recombinant activated Factor VIIa (rFVIIa), or other coagulation factor products, in the 24 hours before study surgery, except when FFP is added to the CPB circuit.