Adjusted Fibrinogen Replacement Strategy (AdFIrst)

May 28, 2025 updated by: Biotest

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 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.

Study Overview

Status

Status

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

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.

Detailed Description

Fibrinogen is the first coagulation factor to become critically reduced during intraoperative bleeding. Therefore, rapid supplementation of fibrinogen to restore physiological plasma levels is an important component in achieving and maintaining hemostasis in bleeding patients. In this study, subjects with major blood loss during elective spinal surgery or abdominal surgery were randomized to receive either intravenous transfusion of the fibrinogen concentrate BT524, or fibrinogen-containing fresh frozen plasma/cryoprecipitate as first hemostatic intervention to rapidly replenish fibrinogen and control bleeding.

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 (Actual)

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.
222

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 Contact Backup

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

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

14 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 spinal surgery or cytoreductive pseudomyxoma peritonei (PMP) 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.

  1. Subjects who underwent spinal surgery: Intra-operative clinically relevant bleeding of approximately 1 Liter, requiring hemostatic treatment during surgery.
  2. Subjects who underwent cytoreductive PMP surgery: Intra-operative prediction of clinically relevant bleeding of more than 2 Liter, requiring hemostatic treatment during surgery

Exclusion Criteria:

  1. Pregnancy or unreliable contraceptive measures or breast feeding (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 IMP
  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 thromboembolic event (TEE) in the preceding 6 months

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: Single

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.
Experimental: BT524
Investigational Human Fibrinogen Concentrate
Biological: BT524
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.
Other Names:
  • Human Fibrinogen concentrate
Active Comparator: Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo)
Standard of Care
Biological: FFP/Cryo
FFP/Cryo was administered intravenously; dosage according to local standards. FFP, 15 mL per kg body weight (BW); Cryoprecipitate, fixed dose of 10 units.
Other Names:
  • Fresh Frozen Plasma
  • Cryoprecipitate

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
Intra-operative Blood Loss
Time Frame: From decision to treat the subject with IMP until end of surgery, an average of 5 hours
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 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
Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration
Time Frame: Prior first dose, 15 minutes after start of first IMP administration
Successful correction of the fibrinogen level is defined as restoring fibrinogen FIBTEM A10 baseline (prior surgery) levels measured by ROTEM (thromboelastometry) 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
Time Frame: prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery
Correction of the fibrinogen level, measured via thromboelastometry (ROTEM/FIBTEM A10), within 15 minutes after IMP start, between 15 and 90 minutes after IMP start, after 90 minutes after IMP start, or unsuccessful correction. The 4 categories were compared between the two treatment arms using a Chi-square test.
prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery
Transfusion Requirements: Cell Salvage
Time Frame: After start of first IMP administration until end of surgery, an average of 5 hours
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
After start of first IMP administration until end of surgery, an average of 5 hours
Transfusion Requirements: Allogeneic Platelets
Time Frame: After start of first IMP administration until end of surgery, an average of 5 hours
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
After start of first IMP administration until end of surgery, an average of 5 hours
Transfusion Requirements: Allogeneic Red Blood Cells
Time Frame: After start of first IMP administration until end of surgery, an average of 5 hours
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
After start of first IMP administration until end of surgery, an average of 5 hours
Transfusion Requirements: Fresh Frozen Plasma
Time Frame: After start of first IMP administration until end of surgery, an average of 5 hours
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
After start of first IMP administration until end of surgery, an average of 5 hours
Transfusion Requirements, Cryoprecipitate
Time Frame: After start of first IMP administration until end of surgery, an average of 5 hours
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
After start of first IMP administration until end of surgery, an average of 5 hours
Amount of Red Blood Cells (RBCs)
Time Frame: After start of first IMP administration until end of surgery, an average of 5 hours
Amount (volume) of RBCs (allogenic and autologous RBCs) infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
After start of first IMP administration until end of surgery, an average of 5 hours
Post-operative Blood Loss
Time Frame: From end of surgery (time of last suture) up to 24 hours after the end of surgery
Post-operative drainage volume in the first 24 hours after end of surgery
From end of surgery (time of last suture) up to 24 hours after the end of surgery
Subjects With Rebleeds
Time Frame: End of surgery up to 8 days after surgery
Proportion (%) of subjects with rebleeds after the end of surgery until day 8
End of surgery up to 8 days after surgery
Hospital Length of Stay After Surgery
Time Frame: From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
Length of stay after surgery (days) = 'date of hospital discharge' minus 'date of surgery'. Where date of discharge is the date of discharge following the IMP treated surgery.
From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
In-hospital Mortality
Time Frame: From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
Number and percentages of subjects who died during hospital stay
From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
Number of Subjects With Thrombosis or Thromboembolic Events (TEEs)
Time Frame: From day of surgery until closing visit (up to 181 days)
Total number of subjects with thrombosis or TEEs documented as treatment-emergent adverse events of special interest
From day of surgery until closing visit (up to 181 days)
Change in Viral Status
Time Frame: Screening visit (up to 42 days prior to surgery) and closing visit (up to 181 days after surgery)
Number of subjects with change in status of viral infections
Screening visit (up to 42 days prior to surgery) and closing visit (up to 181 days after surgery)

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.
Biotest

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ICON Clinical Research
PRA Health Sciences

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.
  • Principal Investigator: Niels Rahe-Meyer, Prof., Franziskus Hospital, Bielefeld

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.
April 3, 2018

Primary Completion (Actual)

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.
September 25, 2023

Study Completion (Actual)

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.
November 21, 2023

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).
December 19, 2017

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.
February 22, 2018

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.
February 23, 2018

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.
June 13, 2025

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 28, 2025

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, 2025

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.
  • 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

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.

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