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.

Study Overview

• Status: Recruiting
• Conditions: Complex Cardiovascular Surgery With Cardiopulmonary Bypass
• Intervention / Treatment: Biological: BE1116; Biological: FFP

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: +1 610-878-4697; Email: clinicaltrials@cslbehring.com

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Not yet recruiting
      • Kingston Health Science Center
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Center - University Campus
    • Toronto, Ontario, Canada, M5B 1W8
      • Not yet recruiting
      • University of Toronto - St. Michael's Hospital (SMH) - Keenan Research Centre for Biomedical Science
  • Quebec
    • Montreal, Quebec, Canada, H1T1C8
      • Not yet recruiting
      • Universite de Montreal-Institut de Cardiologie de Montreal (ICM) Montreal Heart Institute (MHI)
• Japan
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Recruiting
      • Kyushu University Hospital
  • Osaka
    • Suita, Osaka, Japan, 564-8565
      • Not yet recruiting
      • National Cerebral and Cardiovascular Center
  • Tokyo
    • Fuchu-shi, Tokyo, Japan, 183-0003
      • Not yet recruiting
      • Sakakibara Heart Institute
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • Not yet recruiting
      • Hospital Civil de Guadalajara
      • Contact: Jamie Lopez Taylor
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Health - Ronald Reagan Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Not yet recruiting
      • University of Chicago Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Medical Center (UMMC)
  • New York
    • Manhasset, New York, United States, 11040
      • Not yet recruiting
      • North Shore University Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • OUHSC (University of Oklahoma Health Sciences Center)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • UT Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Not yet recruiting
      • University of Virginia Health System
      • Contact: John McNeil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fresh frozen plasma	Biological: FFP; A single dose of FFP will be administered as investigational product (IP) by IV infusion intraoperatively.
Experimental: BE1116	Biological: BE1116; A single dose of BE1116 will be administered by intravenous (IV) infusion intraoperatively.; Other Names: 4F-PCC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With and Without a Successful Correction of Coagulation Factor Deficiency	Successful correction ("yes" vs "no") of coagulation factor deficiency as measured by an international normalized ratio (INR) of less than or equal to (≤) 1.4 at 30 minutes after the end of IP infusion.	At Day 1 after IP infusion (30 minutes after the end of infusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Effective or Not Effective Hemostatic Response from 30 Minutes to 24 Hours After the End of IP Infusion	The hemostatic response will be recorded as either effective or not effective. 'Effective' is defined as no hemostatic intervention was required, whereas 'non effective' is defined as a hemostatic intervention was required in the period from 30 minutes to 24 hours after the end of IP infusion. Hemostatic intervention includes surgical re-intervention for bleeding and / or the administration of any systemic hemostatic agents.	Up to 24 hours after the end of IP infusion
Change in INR from Baseline		From baseline (before IP infusion), to 30 minutes, 6 hours, 24 hours, and 48 hours after the end IP infusion
Number of Participants With Effective and Not Effective Hemostatic Response From the Start of IP Infusion to 24 Hours After the Start of IP Infusion	The hemostatic response will be recorded as either effective or not effective. 'Effective' is defined as no hemostatic intervention was required, whereas 'non effective' is defined as a hemostatic intervention was required in the period from the start of IP infusion to 24 hours after the start of IP infusion. Hemostatic intervention includes surgical re-intervention for bleeding and / or the administration of any systemic hemostatic agents.	Up to 24 hours after the start of IP infusion
Number of Participants in Each Universal Definition for Perioperative Bleeding (UDPB) Class	Bleeding is assessed based on 9 events occurring during surgery or within the first postoperative day. These 9 events will be used to determine UDPB class ranging from Class 0 to 5 as follows: Class 0 (insignificant), Class 1 (mild), Class 2 (moderate), Class 3 (severe), and Class 4 (massive).	During surgery (Day 1) and on the first postoperative day (Day 2)
Total Number of Units of Allogeneic Blood Products (ABPs) Administered	The ABPs include whole blood, cryoprecipitate, platelets, red blood cells (RBCs), and FFP (except the dose administered as IP). For the purposes of this study, a dose of fibrinogen concentrate will be counted as an ABP, because it is administered in lieu of cryoprecipitate.	From the start of IP infusion and up to 24 hours and 5 days after surgery
Number of Units of Individual ABPs Administered	The ABPs include whole blood, cryoprecipitate, platelets, RBCs, and FFP (except the dose administered as IP). For the purposes of this study, a dose of fibrinogen concentrate will be counted as an ABP, because it is administered in lieu of cryoprecipitate.	Up to 24 hours after the start of IP infusion
Volume of Chest Tube Output		Up to 24 hours after the end of surgery
Number of Participants Requiring Reoperation for Bleeding and for Other Reasons		Up to 30 days after surgery
Duration of Mechanical Ventilation	The duration of mechanical ventilation is defined as the number of days on mechanical ventilation after the study surgery. If there are multiple incidences of mechanical ventilation, the duration will be the sum of the number of days for all incidences.	Up to 30 days after surgery
Duration of Primary Intensive Care Unit (ICU) Stay	The duration of primary ICU stay is defined as the number of days in the ICU after the study surgery.	Up to 30 days after surgery
Duration of Primary Hospital Stay	The duration of primary hospital stay is defined as the duration in calendar days from the date of IP administration to the date of primary hospital discharge, or death in the hospital, or end of study (EOS) visit, whichever occurs first.	Up to 30 days after surgery
Number of Deaths		Up to Day 1 during the primary hospital stay, and within 28 days following IP infusion
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)		Up to 30 days after IP infusion
Change in Plasma Concentrations of Coagulation Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX), and Proteins C and S From Baseline		From baseline to 30 minutes after the end of IP infusion
Plasma Concentrations of Coagulation FII, FVII, FIX, and FX and Proteins C and S		Up to 48 hours after the end of IP infusion
Number of Participants With and Without Successful Correction of Coagulation Factor Deficiency	Successful correction ("Yes or No") of coagulation factor deficiency measured by a rotational thromboelastometry (ROTEM) extrinsically activated thromboelastometric test (EXTEM) clotting time (CT) ≤ 80 seconds or thromboelastography (TEG) reaction time ≤ 8 minutes. ROTEM and TEG are viscoelastic coagulation tests that quantify the process of clot formation and degradation.	At Day 1 after IP infusion (30 minutes after the end of infusion)
Change in Z-Scores for ROTEM EXTEM CT and TEG Reaction Time	Measurements on either ROTEM EXTEM CT or TEG reaction time will be collected. To combine these measurements, z-scores will be calculated for each method of measurement. The z-score standardizes each measurement by subtracting the mean and dividing by the standard deviation of the respective method.	From baseline (before IP infusion) to 30 minutes and 24 hours after the end IP infusion
Change in Bleeding Severity Scale (BSS) Score From Baseline	The BSS is a validated intraoperative scale used in clinical studies of hemostatic agents as a measure of bleeding severity. Bleeding is scored on a scale from 0 (no bleeding) to 4 (unidentified or inaccessible spurting or gush). A lower score indicates a better outcome.	From baseline (before IP infusion) to 30 minutes after end of IP infusion

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): December 17, 2026

Study Registration Dates

• First Submitted: July 14, 2025
• First Submitted That Met QC Criteria: July 28, 2025
• First Posted (Actual): July 30, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cardiopulmonary bypass; Fresh frozen plasma; Coagulopathic Bleeding; Coagulation factor deficiency; Prothrombin complex concentrates
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Enzymes and Coenzymes; Blood Proteins; Blood Coagulation Factors; Enzyme Precursors; Protein Precursors; Factor IX
• Other Study ID Numbers: BE1116_3008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.

IPD Sharing 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 has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No