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

May 8, 2026 updated by: CSL Behring

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With and Without a Successful Correction of Coagulation Factor Deficiency
Time Frame: At Day 1 after IP infusion (30 minutes after the end of infusion)
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
Time Frame: Up 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
Time Frame: From baseline (before IP infusion), to 30 minutes, 6 hours, 24 hours, and 48 hours after the end IP infusion
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
Time Frame: Up 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
Time Frame: During surgery (Day 1) and on the first postoperative day (Day 2)
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
Time Frame: From the start of IP infusion and up to 24 hours and 5 days after surgery
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
Time Frame: Up to 24 hours after the start of IP infusion
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
Time Frame: Up to 24 hours after the end of surgery
Up to 24 hours after the end of surgery
Number of Participants Requiring Reoperation for Bleeding and for Other Reasons
Time Frame: Up to 30 days after surgery
Up to 30 days after surgery
Duration of Mechanical Ventilation
Time Frame: Up to 30 days after surgery
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
Time Frame: Up to 30 days after surgery
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
Time Frame: Up to 30 days after surgery
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
Time Frame: Up to Day 1 during the primary hospital stay, and within 28 days following IP infusion
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)
Time Frame: Up to 30 days after IP infusion
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
Time Frame: From baseline to 30 minutes after the end of IP infusion
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
Time Frame: Up to 48 hours after the end of IP infusion
Up to 48 hours after the end of IP infusion
Number of Participants With and Without Successful Correction of Coagulation Factor Deficiency
Time Frame: At Day 1 after IP infusion (30 minutes after the end of infusion)
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
Time Frame: From baseline (before IP infusion) to 30 minutes and 24 hours after the end IP infusion
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
Time Frame: From baseline (before IP infusion) to 30 minutes after end of IP infusion
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CSL Behring

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Study Director, CSL Behring

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 18, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 17, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Complex Cardiovascular Surgery With Cardiopulmonary Bypass

Clinical Trials on BE1116

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings