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Completed

NCT Number: NCT03444324

Adjusted Fibrinogen Replacement Strategy

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.

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Key information

Conditions

Bleeding Disorder Afibrinogenemia Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Cardiovascular Diseases Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hypofibrinogenemia; Acquired Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Site 02, Jette, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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:

5.

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Other names: Human Fibrinogen concentrate

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.

Other names: Fresh Frozen Plasma, Cryoprecipitate

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

Sponsors and collaborators

Lead sponsor

Biotest

Industry

Collaborators

  • ICON Clinical Research
  • PRA Health Sciences

Registry information

Official study title

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)

Acronym: AdFIrst

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Feb 23, 2018
Registry last updated
Jun 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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