Adjusted Fibrinogen Replacement Strategy (AdFIrst)

A Randomized, Active-controlled, Multicenter, Phase III Study Investigating Efficacy and Safety of Intra-operative Use of BT524 (Human Fibrinogen Concentrate) in Subjects Undergoing Major Spinal or Abdominal Surgery (AdFIrst)

The purpose of this study is to investigate efficacy and safety of fibrinogen concentrate BT524, when administered to patients with major blood loss during elective spine surgery.The study aims to demonstrate that BT524 is at least not worse than the comparator fresh frozen plasma in reducing intra-operative blood loss.

Study Overview

• Status: Completed
• Conditions: Bleeding Disorder; Hypofibrinogenemia; Acquired
• Intervention / Treatment: Biological: BT524; Biological: FFP/Cryo

Detailed Description

Fibrinogen is the first coagulation factor to become critically reduced during intra-operative bleeding. Therefore, rapid fibrinogen supplementation to restore physiological plasma levels is an important component to achieve and maintain hemostasis in bleeding patients. In this study, patients with major blood loss during elective spine surgery will be randomized 1:1 to a single intravenous transfusion of the fibrinogen concentrate BT524 or to fibrinogen-containing fresh frozen plasma (FFP).

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Judith Wessels-Kranz, PhD; Phone Number: 6395 00496103801; Email: judith.wessels-kranz@biotest.com
• Study Contact Backup: Name: Joachim Schütze, PhD; Phone Number: 5127 00496103801; Email: joachim.schuetze@biotest.com

Study Locations

• Belgium
  • Jette, Belgium
    • Site 02
  • Leuven, Belgium
    • Site 01
• Czechia
  • Brno, Czechia
    • Site 54
  • Prague, Czechia
    • Site 51
  • Prague, Czechia
    • Site 53
  • Usti Nad Labem, Czechia
    • Site 52
• Germany
  • Bielefeld, Germany
    • Site 15
  • Bonn, Germany
    • Site 11
  • Hannover, Germany
    • Site 12
  • München, Germany
    • Site 14
  • Münster, Germany
    • Site 13
• Poland
  • Warschau, Poland
    • Site 21
• Spain
  • Barcelona, Spain
    • Site 31
  • Barcelona, Spain
    • Site 32
  • Barcelona, Spain
    • Site 33
  • Barcelona, Spain
    • Site34
• Switzerland
  • Liestal, Switzerland
    • Site 41
  • Zürich, Switzerland
    • Site 43
• United Kingdom
  • Basingstoke, United Kingdom
    • Site 71

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

At screening:

1. Written informed consent
2. Subjects scheduled for elective major spine surgery with expected major blood loss
3. Male or female, aged ≥ 18 years

4. No increased bleeding risk as assessed by standard coagulation tests and medical history

   Intra-operative:

5. Intra-operative bleeding > 1,000 mL (total blood loss), resulting in a high risk for the need of FFP transfusion during surgery.

Exclusion Criteria:

1. Pregnancy or unreliable contraceptive measures or lactation period (women only)
2. Hypersensitivity to proteins of human origin or known hypersensitivity reactions to components of the Investigational Medicinal Products (IMP)
3. Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study
4. Treatment with any fibrinogen concentrate and/or fibrinogen-containing product within 30 days prior to infusion of BT524
5. Employee or direct relative of an employee of the Contract Research Organization (CRO), the study site, or Biotest
6. Inability or lacking motivation to participate in the study
7. 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
8. Presence or history of venous/arterial thrombosis or TEE in the preceding 6 months -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BT524; Investigational Human Fibrinogen Concentrate	Biological: BT524; BT524 is administered intravenously, patient specific dosage calculated based on body weight and fibrinogen level.; Other Names: Human Fibrinogen concentrate
Active Comparator: Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo); Standard of Care	Biological: FFP/Cryo; FFP/Cryo is administered intravenously; dosage according to local standards in mL per kg body weight.; Other Names: Fresh Frozen Plasma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Decision to treat until end of surgery, expected average of 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correction of the fibrinogen level	Proportion (%) of subjects with successful correction of fibrinogen level	15 minutes after start of IMP administration
Transfusion requirements	Total amount of transfusion products	After end of IMP administration until end of surgery, expected average of 2 hours
24 hours post-operative blood loss	Drainage volume	1 day after surgery
Subjects with rebleeds	Proportion (%) of subjects	8 days after surgery
Hospital length of stay	Days in hospital after surgery	35 days after surgery
In-Hospital mortality	Number of death during hospital stay	35 days after surgery
Adverse events	Number of adverse events	35 days after surgery
Virus status	Number of subjects with viral infection	35 days after surgery
Thrombosis and of thromboembolic events	Frequency and severity	35 days after surgery

Collaborators and Investigators

• Sponsor: Biotest
• Collaborators: PRA Health Sciences
• Investigators: Principal Investigator: Niels Rahe-Meyer, Prof., Franziskus Hospital, Bielefeld

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): September 25, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Fibrinogen
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders
• Other Study ID Numbers: 995; 2017-001163-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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