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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

Efficacy and safety of 4F-PCC in adult patients undergoing complex cardiovascular surgery with cardiopulmonary bypass

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

JPN-CHIKEN@csl.com.au

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

+81-3-4213-0191

JPN-CHIKEN@csl.com.au

Recruiting

Feb. 01, 2026

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Adult greater than or equal to (>=) 18 years and has providedwritten informed consent.
2. Undergoing elective complex cardiovascular surgery requiring cardiopulmonary bypass, including procedures of the thoracic aorta (with or without additionalcardiac interventions), aortic valve replacement + coronary arterybypass graft (CABG), complex valve surgeries, mitral valve repair + CABG, and mitral valve replacement + CABG and reoperative CABG. Reoperative procedures are permitted. Excluded surgeries are asfollows: heart transplantation, insertion or removal of ventricularassist devices (except for intra-aortic balloon pumps), and acuterepair of thoracoabdominal aneurysms.
3. Coagulation factor replacement (ie, 4-Factor prothrombin complex concentrate [4F-PCC] or fresh frozen plasma [FFP]) is ordered inthe operating room for the management of bleeding, in accordancewith accepted clinical standards. The following criteria must be met:
- International normalized ratio (INR) >= 1.6 (point-of-care INR testing by Hemochron at least 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 surgicalcomplications), as defined by a Bleeding Severity Scale (BSS) score of >= 2.

Administration of any systemic hemostatic therapy, such ascryoprecipitate, platelets, FFP, PCC (eg, 4F-PCC / 3F-PCC), Factor VIII (FVIII) inhibitor bypassing activity(FEIBA), recombinant activated Factor VIIa (rFVIIa), or othercoagulation factor products, in the 24 hours before study surgery,except when FFP is added to the cardiopulmonary bypass circuit.

Both

Complex cardiovascular surgery with cardiopulmonary bypass

A single dose of BE1116 or FPP will be administered by intravenous infusion intraoperatively.

Cardiopulmonary bypass; Coagulopathic bleeding; Coagulation factor deficiency; Prothrombin complex concentrates; Fresh frozen plasma

Successful correction (yes vs no) of coagulation factor deficiency as measured by an INR of <= 1.4 at 30 minutes after the end of investigational product (IP) infusion.

1 Hemostatic response (effective vs not effective) from 30 minutes to 24 hours after the end of IP infusion.
2 Successful correction (yes vs no) of coagulation factor deficiency as measured by a rotational thromboelastometry (ROTEM) extrinsically activated thromboelastometric test (EXTEM) clotting time (CT)<= 80 seconds or thromboelastography (TEG) reaction time <= 8 minutes at 30 minutes after the end of IP infusion.
3 Change in INR from baseline to 30 minutes, and 6, 24, and 48 hours after the end of IP infusion.
4 Hemostatic response (effective vs not effective) from the start of IP infusion to 24 hours after the start of IP infusion.
5 Change in z-scores for ROTEM EXTEM CT and TEG reaction time from baseline to 30 minutes, and 6 and 24 hours after the end of IP infusion.
6 Change in BSS score from baseline to 30 minutes after the end of IP infusion.
7 Universal Definition for Perioperative Bleeding classes based on events occurring during surgery or within the first postoperative day.
8 Total number of units of allogeneic blood products (ABPs) administered from the start of IP infusion and up to 5 days after surgery.
9 Total number of units of ABPs administered up to 24 hours after the start of IP infusion.
10 Number of units of individual ABPs administered up to 24 hours after the start of IP infusion.
11 Volume of chest tube output up to 24 hours after the end of study surgery.
12 Need for reoperation for bleeding and for other reasons up to 30 days after surgery.
13 Duration of mechanical ventilation up to 30 days after surgery.
14 Duration of primary intensive care unit stay and primary hospital stay up to 30 days after surgery.
15 28-Day and in-hospital mortality .
16 Treatment-emergent adverse events (TEAEs), serious TEAEs, and adverse events of special interest up to 30 days after IP infusion up to 30 days after surgery.
17 Change in plasma concentrations of coagulation FII, FVII, FIX, and FX, and Proteins C and S, from baseline to 30 minutes after the end of IP infusion.
18 Plasma concentrations of coagulation FII, FVII, FIX, and FX, and Proteins C and S, over time up to 48 hours after the end of IP infusion.

Oct. 27, 2025

Yes

Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Supporting information: Protocol and Statistical Analysis Plan (SAP) will also be provided. Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available. Access Criteria: Proposed research should seek to answer a previously unanswered important medical or scientific question. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that have been appropriately anonymized will be available.

United States/Canada/Mexico