Adjusted Fibrinogen Replacement Strategy

NCT03444324 | Completed Phase 3 Results DMC

• 2 other identifiers: 9952017-001163-20
• Study Type: interventional
• Target: 222
• Locations: 7 countries
• Sites: 19

Brief Summary

The main purpose of this study was to demonstrate the efficacy and safety of intraoperative use of fibrinogen concentrate BT524, as a complementary therapy for the management of uncontrolled severe hemorrhage in acquired hypofibrinogenemia. This non-inferiority study focused on the primary objective of demonstrating that BT524 is non-inferior that means not worse than the comparator fresh frozen plasma/cryoprecipitate in reducing intraoperative blood loss when administered intravenously in subjects with acquired hypofibrinogenemia undergoing elective major spinal or abdominal surgery.

Conditions

Bleeding Disorder; Hypofibrinogenemia; Acquired

Keywords

Fibrinogen

Outcome Measures

Primary Outcomes (1)

• Intra-operative Blood Loss

  Intra-operative blood loss as measured by amount of blood from blood suction unit and amount of blood from surgical cloths and compresses.

  From decision to treat the subject with IMP until end of surgery, an average of 5 hours

Secondary Outcomes (14)

• Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration

  Prior first dose, 15 minutes after start of first IMP administration

• Time to First Successful Correction of Fibrinogen Level

  prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery

• Transfusion Requirements: Cell Salvage

  After start of first IMP administration until end of surgery, an average of 5 hours

• Transfusion Requirements: Allogeneic Platelets

  After start of first IMP administration until end of surgery, an average of 5 hours

• Transfusion Requirements: Allogeneic Red Blood Cells

  After start of first IMP administration until end of surgery, an average of 5 hours

Study Arms (2)

BT524

EXPERIMENTAL

Investigational Human Fibrinogen Concentrate

Biological: BT524

Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo)

ACTIVE COMPARATOR

Standard of Care

Biological: FFP/Cryo

Interventions

BT524 BIOLOGICAL

BT524 was administered intravenously at a patient specific dosage depending on the type of surgery, the extent of bleeding and the subject's clinical condition.

Also known as: Human Fibrinogen concentrate

BT524

FFP/Cryo BIOLOGICAL

FFP/Cryo was administered intravenously; dosage according to local standards. FFP, 15 mL per kg body weight (BW); Cryoprecipitate, fixed dose of 10 units.

Also known as: Fresh Frozen Plasma, Cryoprecipitate

Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At screening:
• Written informed consent
• Subjects scheduled for elective major spinal surgery or cytoreductive pseudomyxoma peritonei (PMP) surgery with expected major blood loss
• Male or female, aged ≥ 18 years
• No increased bleeding risk as assessed by standard coagulation tests and medical history
• Intra-operative:
• Subjects who underwent spinal surgery: Intra-operative clinically relevant bleeding of approximately 1 Liter, requiring hemostatic treatment during surgery.
• Subjects who underwent cytoreductive PMP surgery: Intra-operative prediction of clinically relevant bleeding of more than 2 Liter, requiring hemostatic treatment during surgery

You may not qualify if:

• Pregnancy or unreliable contraceptive measures or breast feeding (women only)
• Hypersensitivity to proteins of human origin or known hypersensitivity reactions to components of the Investigational Medicinal Products (IMP)
• Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study
• Treatment with any fibrinogen concentrate and/or fibrinogen-containing product within 30 days prior to infusion of IMP
• Employee or direct relative of an employee of the Contract Research Organization (CRO), the study site, or Biotest
• Inability or lacking motivation to participate in the study
• Medical condition, laboratory finding (e.g., clinically relevant biochemical or hematological findings outside the normal range), or physical exam finding that in the opinion of the investigator precludes participation
• Presence or history of venous/arterial thrombosis or thromboembolic event (TEE) in the preceding 6 months

Sponsors & Collaborators

• Biotest: lead
• PRA Health Sciences: collaborator
• ICON Clinical Research: collaborator

Study Sites (19)

Site 02

Jette, Belgium

Location

Site 01

Leuven, Belgium

Location

Site 54

Brno, Czechia

Location

Site 51

Prague, Czechia

Location

Site 53

Prague, Czechia

Location

Site 52

Ústí nad Labem, Czechia

Location

Site 15

Bielefeld, Germany

Location

Site 11

Bonn, Germany

Location

Site 12

Hanover, Germany

Location

Site 14

München, Germany

Location

Site 13

Münster, Germany

Location

Site 21

Warsaw, Poland

Location

Site 31

Barcelona, Spain

Location

Site 32

Barcelona, Spain

Location

Site 33

Barcelona, Spain

Location

Site34

Barcelona, Spain

Location

Site 41

Liestal, Switzerland

Location

Site 43

Zurich, Switzerland

Location

Site 71

Basingstoke, United Kingdom

Location

Related Publications (1)

• Rahe-Meyer N, Roy A, Trouillier HH, Schimo S, Wessels-Kranz J, Abraha S, Staus A, Balaban U, Hader T, Schuttrumpf J, Aigner S, Bohm H. Efficacy and safety of human fibrinogen concentrate (BT524) in patients with major haemorrhage undergoing major orthopaedic or abdominal surgery (AdFIrst): a randomised, active-controlled, multicentre, partially blinded, phase 3 non-inferiority trial. EClinicalMedicine. 2025 Jun 7;85:103264. doi: 10.1016/j.eclinm.2025.103264. eCollection 2025 Jul.

  PMID: 40741224 DERIVED

MeSH Terms

Conditions

Hemostatic Disorders; Afibrinogenemia

Interventions

cryoprecipitate coagulum

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Coagulation Protein Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Christina Erb
• Organization: Biotest AG

christina.erb@biotest.com

00496103801

Study Officials

• Niels Rahe-Meyer, Prof.

  Franziskus Hospital, Bielefeld

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Study 995 was partially blinded; surgeon, surgical staff and subjects were blinded to treatment allocation throughout the entire surgery. The subject was blinded throughout the study. The Investigational Medicinal Product (IMP), BT524 or FFP/Cryo, was administered by an unblinded anaesthesiologist.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients were randomly assigned to treatment with BT524 or FFP/Cryo.

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: February 23, 2018
• Study Start: April 3, 2018
• Primary Completion: September 25, 2023
• Study Completion: November 21, 2023
• Last Updated: June 13, 2025
• Results First Posted: June 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); CZ (4); CH (2); GB (1); BE (2); DE (5); PL (1)