Adjusted Fibrinogen Replacement Strategy (AdFIrst)

Biotest

Status and phase: Completed; Phase 3

Conditions: Bleeding Disorder; Hypofibrinogenemia; Acquired

Treatments: Biological: FFP/Cryo; Biological: BT524

Study type: Interventional

Funder types: Industry

Identifiers

NCT03444324

995

2017-001163-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 339 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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:

6. Subjects who underwent spinal surgery: Intra-operative clinically relevant bleeding of approximately 1 L, requiring hemostatic treatment during surgery.

7. Subjects who underwent cytoreductive PMP surgery: Intra-operative prediction of clinically relevant bleeding of more than 2 L, 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 TEE in the preceding 6 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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339 participants in 2 patient groups

BT524

Experimental group

Description:

Investigational Human Fibrinogen Concentrate

Treatment:

Biological: BT524

Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo)

Active Comparator group

Description:

Standard of Care

Treatment:

Biological: FFP/Cryo