Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study )

A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Large Simple Trial Evaluating the Use of BE1116 (4-Factor Prothrombin Complex Concentrate [Kcentra® / Beriplex®]) to Improve Survival in Patients With Traumatic Injury and Acute Major Bleeding

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, large simple trial to investigate the efficacy and safety of a single intravenous (IV) infusion of BE1116 in subjects who have traumatic injury, with confirmed or suspected acute major bleeding and / or predicted to receive a large volume blood product transfusion.

Study Overview

• Status: Terminated
• Conditions: Traumatic Injury
• Intervention / Treatment: Drug: Placebo; Drug: BE1116

• Study Type: Interventional
• Enrollment (Actual): 1366
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Liverpool
    • Sydney, Liverpool, Australia, NSW 2170
      • Liverpool Hospital
  • New Lambton
    • Sydney, New Lambton, Australia, 2305
      • John Hunter Hospital
  • New South Wales
    • Sydney, New South Wales, Australia
      • Royal Prince Alfred Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide
  • Sydney
    • Kogarah, Sydney, Australia
      • St. George Hospital
    • Westmead, Sydney, Australia, 2145
      • Westmead Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth Hospital
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge Addenbrookes University
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry
  • Hull, United Kingdom, HU3 2JZ
    • Hull Royal Infirmary Hull University Teaching Hospitals NHS Trust
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Teaching Hospital
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital
  • London, United Kingdom, SW17 0QT
    • St. Georges Hospital
  • London, United Kingdom, SW7 1LY
    • Imperial College Healthcare
  • Newcastle upon Tyne, United Kingdom, NE14LP
    • Royal Victoria Infirmary
  • Nottingham, United Kingdom, NG7 2UH
    • Queen's Medical Centre, Nottingham University Hospitals NHS Trust
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Sheffield Teaching Hospital
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • UAB Hospital
    • Mobile, Alabama, United States, 36507
      • University of South Alabama
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Chandler Regional Medical Center
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
    • Phoenix, Arizona, United States, 85006
      • Banner - University Medical Center Phoenix
    • Phoenix, Arizona, United States, 85008
      • Valleywise Medical Center
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Scottsdale Osborn Medical Center
    • Tucson, Arizona, United States, 85719
      • University Medical Center Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • UAMS Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90033
      • LAC+USC Medical Center
    • Moreno Valley, California, United States, 92555
      • Riverside University Health System Medical Center
    • Orange, California, United States, 92868
      • UC Irvine
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital and Trauma Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Aurora
    • Colorado Springs, Colorado, United States, 80909
      • UC Health Memorial Hospital Central
    • Denver, Colorado, United States, 80204
      • Denver Health and Hospital Authority
    • Loveland, Colorado, United States, 80538
      • Medical Center of the Rockies
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington University Hospital
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Washington Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Uf Health Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami/Ryder Trauma Center
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Health System
    • Macon, Georgia, United States, 31201
      • Atrium Health - Medical Center of central Georgia
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent's Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Methodist Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Albert B. Chandler Hospital
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center of New Orleans
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Hospital
    • Saint Paul, Minnesota, United States, 55101
      • Health Partners Regions Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center (UMMC)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital
    • St Louis, Missouri, United States, 63104
      • SSM Health St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • UNMC (University of Nebraska Medical Center)
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Health Care
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
    • Trenton, New Jersey, United States, 08638
      • Capital Health Regional Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
    • Mineola, New York, United States, 11501
      • NYU Langone
    • Richmond Hill, New York, United States, 11418
      • Jamaica Hospital Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Sanford Medical Center Fargo
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Toledo, Ohio, United States, 43608
      • Mercy Health - St. Vincent Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Science Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Sciences University Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center Presbyterian
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Brown University (Rhode Island Hospital)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
      • Sanford USD Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Baroness Hospital
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center - UTMCK
    • Memphis, Tennessee, United States, 38103
      • Regional Medical Center
    • Nashville, Tennessee, United States, 37027
      • Vanderbilt Hospital and Clinics
  • Texas
    • Austin, Texas, United States, 78701
      • Dell Seton Medical Center
    • El Paso, Texas, United States, 79905
      • University Medical Center El Paso
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Fort Worth, Texas, United States, 76134
      • JPS Health Network (John Peter Smith Hospital)
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital - Baylor Medical Center - Harris Health Network
    • San Antonio, Texas, United States, 78229
      • University Hospital
    • Tyler, Texas, United States, 75701
      • UT Health Tyler
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • J.W. Ruby Memorial Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• (a) Estimated age ≥ 15 years. Older minimum age is required in some locations. FOR United Kingdom: Estimated or actual age ≥ 16 years FOR Australia: Estimated or actual age ≥ 18 years AND (b) Estimated or actual weight ≥ 50 kg (110 lbs).
• Traumatic injury with confirmed or suspected acute major bleeding and/or Revised Assessment of Bleeding and Transfusion (RABT) score ≥ 2
• Activation of massive transfusion protocol

Exclusion Criteria:

• Healthcare professional cardiopulmonary resuscitation including chest compressions for ≥ 5 consecutive minutes at any time before randomization
• Isolated penetrating or blunt cranial injury, or exposed brain matter
• Isolated burns estimated to be > 20% total body surface area or suspected inhalational injury
• Known anticoagulation treatment or a history of a TEE, within the past 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BE1116; Administration by IV infusion	Drug: BE1116; 4-Factor Prothrombin Complex administered by intravenous (IV) infusion; Other Names: 4-Factor Prothrombin Complex; Kcentra®; Beriplex®
Placebo Comparator: Placebo; Administration by IV infusion	Drug: Placebo; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With All-cause 6-hour Mortality	Here, the percentage of participants with all-cause mortality has been reported. Percentages were rounded off if the second digit after the decimal point is equal to or more than five.	Up to 6 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With All-cause 24-hour In-hospital Mortality	In-hospital mortality up to 24 hours after randomization was recorded and assessed for the primary hospitalization only. Here, the percentage of participants with all-cause in hospital mortality has been reported. Percentages were rounded off if the second digit after the decimal point is equal to or more than five.	Up to 24 hours after randomization
Proportion of Participants With All-cause In-hospital Mortality Up to 30 Days After Randomization	In-hospital mortality was recorded and assessed for the primary hospitalization only. Here, the percentage of participants with all-cause in hospital mortality has been reported. Percentages were rounded off if the second digit after the decimal point is equal to or more than five.	Up to 30 days after randomization
Proportion of Participants Who Underwent Surgical or Interventional Radiological Procedures to Stop Bleeding Related to the Primary Injury	Here, the percentage of participants with who underwent surgical or interventional radiological procedures to stop bleeding related to the primary injury has been reported. Percentages were rounded off if the second digit after the decimal point is equal to or more than five.	Up to 24 hours after randomization
Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	The number of participants with treatment-emergent SAEs considered related to IP that occurred during primary hospitalization within the 30 days after randomization are summarized by treatment arm.	Up to 30 days after randomization
Number of Participants With In-hospital Overall and Related Thromboembolic Events (TEEs)	The TEEs may be symptomatic or asymptomatic, and arterial or venous (eg, deep vein thrombosis, pulmonary embolism, ischemic stroke [including thromboembolic stroke], myocardial infarction). The observed in-hospital overall and related to IP TEEs are reported here.	Up to 30 days after randomization
Number of Participants With Acute Respiratory Distress Syndrome (ARDS)	ARDS will be assessed using the Berlin definition based on four criteria: timing, chest imaging, origin of edema, oxygenation (mild, moderate or severe) and high-flow nasal oxygen.	Up to 30 days after randomization
Number of Participants With Multiple Organ Failure	Multiple organ failure will be assessed using the Denver post injury multiple organ failure score. The Denver score rates the dysfunction of 4 organ systems (pulmonary, renal, hepatic, and cardiac), which are each graded on a scale from 0 to 3, where 0 represents "mild" and 3 was "severe". Multiple organ failure is defined as a score > 3.	Up to 30 days after randomization
Number of Participants With Acute Kidney Injury (AKI) Requiring Renal Replacement Therapy	Renal replacement therapy included dialysis, hemofiltration, or hemodiafiltration. AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines is diagnosed if any one of the following happens: • Serum creatinine increases by ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 hours • Serum creatinine increases to ≥ 1.5 times the baseline level, within the past 7 days • Urine levels drops to less than 0.5 mL/kg/hour for 6 hours	Up to 30 days after randomization

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Actual): October 29, 2024
• Study Completion (Actual): October 29, 2024

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Hemostatics; Coagulants; factor IX, factor VII, factor X, prothrombin drug combination
• Other Study ID Numbers: BE1116_3006; 2021-005060-21 (EudraCT Number)

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