Comparing 4F‑PCC (BE1116) and fresh frozen plasma to treat bleeding during complex heart surgery with cardiopulmonary bypass

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 trial tests whether BE1116 (a 4‑factor prothrombin complex concentrate) works better than fresh frozen plasma to correct clotting problems in adults who bleed during complex heart surgery with cardiopulmonary bypass.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: CSL Behring (industry)
• Locations: 18 sites (Los Angeles, California and 17 other locations)
• Trial ID: NCT07094087 on ClinicalTrials.gov

What this trial studies

This is a phase 3, multicenter, randomized, open‑label, parallel‑group controlled study comparing BE1116 (4F‑PCC) with fresh frozen plasma (FFP) in adults undergoing complex cardiovascular surgery with cardiopulmonary bypass (CPB). Eligible participants are adults having elective complex procedures requiring CPB who develop bleeding and for whom coagulation factor replacement is ordered intraoperatively. Treatment is given in the operating room after protamine reversal when point‑of‑care INR criteria are met, and patients are randomized to receive BE1116 or FFP. The study's primary focus is on correcting coagulation factor deficiencies and monitoring safety outcomes between the two groups.

Who should consider this trial

Good fit: Adults (≥18 years) scheduled for elective complex cardiovascular surgery with CPB who develop intraoperative bleeding and require coagulation factor replacement (meeting the protocol INR criteria) are the ideal candidates.

Not a fit: Patients who do not develop coagulopathic bleeding during CPB, those undergoing excluded procedures (for example heart transplant or most VAD insertions/removals), or those unable to receive PCC or plasma are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, BE1116 could restore clotting faster with smaller infusion volumes than plasma, potentially reducing transfusion burden and related complications.

How similar studies have performed: Previous studies of 4‑factor PCCs for warfarin reversal and perioperative bleeding have shown faster INR correction and lower volume needs than FFP, but large randomized phase‑3 comparisons specifically in complex CPB surgery are limited.

Eligibility criteria

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.

Where this trial is running

Los Angeles, California and 17 other locations

• UCLA Health - Ronald Reagan Medical Center — Los Angeles, California, United States (RECRUITING)
• University of Chicago Medicine — Chicago, Illinois, United States (NOT_YET_RECRUITING)
• University of Maryland Medical Center (UMMC) — Baltimore, Maryland, United States (RECRUITING)
• North Shore University Hospital — Manhasset, New York, United States (NOT_YET_RECRUITING)
• University of Cincinnati — Cincinnati, Ohio, United States (RECRUITING)
• OUHSC (University of Oklahoma Health Sciences Center) — Oklahoma City, Oklahoma, United States (RECRUITING)
• Oregon Health & Sciences University — Portland, Oregon, United States (RECRUITING)
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (RECRUITING)
• UT Southwestern Medical Center — Dallas, Texas, United States (NOT_YET_RECRUITING)
• University of Virginia Health System — Charlottesville, Virginia, United States (NOT_YET_RECRUITING)
• Kingston Health Science Center — Kingston, Ontario, Canada (NOT_YET_RECRUITING)
• London Health Sciences Center - University Campus — London, Ontario, Canada (RECRUITING)
• University of Toronto - St. Michael's Hospital (SMH) - Keenan Research Centre for Biomedical Science — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• Universite de Montreal-Institut de Cardiologie de Montreal (ICM) Montreal Heart Institute (MHI) — Montreal, Quebec, Canada (NOT_YET_RECRUITING)
• Kyushu University Hospital — Fukuoka, Fukuoka, Japan (RECRUITING)
• National Cerebral and Cardiovascular Center — Suita, Osaka, Japan (NOT_YET_RECRUITING)
• Sakakibara Heart Institute — Fuchu-shi, Tokyo, Japan (NOT_YET_RECRUITING)
• Hospital Civil de Guadalajara — Guadalajara, Jalisco, Mexico (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Trial Registration Coordinator

Conditions: Complex Cardiovascular Surgery With Cardiopulmonary Bypass, Cardiopulmonary bypass, Coagulopathic Bleeding, Coagulation factor deficiency, Prothrombin complex concentrates, Fresh frozen plasma