Adjusted Fibrinogen Replacement Strategy

Phase 3

Completed

• Conditions: Bleeding Disorder; Hypofibrinogenemia; Acquired
• Interventions: Biological: BT524; Biological: FFP/Cryo

• Registration Number: NCT03444324
• Lead Sponsor: Biotest

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.

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 Timeline

• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2018-02-22
• Study First Posted: 2018-02-23
• Study Start: 2018-04-03
• Primary Completion: 2023-09-25
• Study Completion: 2023-11-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 339

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BT524	BT524	Investigational Human Fibrinogen Concentrate
Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo)	FFP/Cryo	Standard of Care

Primary Outcome Measures

Name	Time	Method
Intra-operative blood loss	From decision to treat the subject with IMP until end of surgery	Intra-operative blood loss as measured by amount of blood from blood suction unit and amount of blood from surgical cloths and compresses.

Secondary Outcome Measures

Name	Time	Method
Proportion (%) of subjects with successful correction of fibrinogen level (FIBTEM A10) 15 minutes after start of first IMP administration	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
Time to first successful correction of fibrinogen level	<=15 minutes, >15 and <=90 minutes, >90 minutes after start of first IMP administration	Correction of the fibrinogen level measured via thromboelastometry (FIBTEM A10) (ROTEM/FIBTEM A10) within 15 minutes after IMP start, between 15 and 90 minutes after IMP start, after 90 minutes after IMP start.
Transfusion requirements, Cell salvage	After start of first IMP administration until end of surgery	Total amount of transfusion products (allogenic blood products) and autologous blood transfusion infused after start of first IMP administration
Transfusion requirements, allogeneic platelets	After start of first IMP administration until end of surgery	Total amount of transfusion products (allogenic blood products) and autologous blood transfusion infused after start of first IMP administration
Transfusion requirements, allogeneic red blood cells	After start of first IMP administration until end of surgery	Total amount of transfusion products (allogenic blood products) and autologous blood transfusion infused after start of first IMP administration
Transfusion requirements, fresh frozen plasma	After start of first IMP administration until end of surgery	Total amount of transfusion products (allogenic blood products) and autologous blood transfusion infused after start of first IMP administration
Transfusion requirements, cryoprecipitate	After start of first IMP administration until end of surgery	Total amount of transfusion products (allogenic blood products) and autologous blood transfusion infused after start of first IMP administration
Amount of red blood cells (RBCs)	After start of first IMP administration until end of surgery	Amount of RBCs (allogenic and autologous RBCs) infused after start of first IMP administration
Post-operative blood loss in the first 24 hours	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
Subjects with rebleeds	End of surgery up to 8 days after surgery	Proportion (%) of subjects with rebleeds after the end of surgery until day 8
Hospital length of stay after surgery	From day of surgery until day of hospital discharge (35 days after surgery)	Length of stay after surgery (days) = date of hospital discharge - date of surgery
In-hospital mortality	From day of surgery to hospital discharge (35 days after surgery)	Number of subjects who died during hospital stay
Number of subjects with serious treatment-emergent adverse events	From day of surgery to closing visit (35 days after surgery)	Total number of subjects with serious adverse events occurring during or after the administration of IMP until the subject's last trial visit
Number of subjects with thrombosis or thromboembolic events (TEEs)	From day of surgery to closing visit (35 days after surgery)	Total number of subjects with thrombosis or TEEs documented as treatment-emergent adverse events of special interest
Change in viral status	Screening visit and Closing Visit (35 days after surgery)	Number of subjects with change in status of viral infections

Trial Locations

Locations (19)

Site 01; 🇧🇪 Leuven, Belgium

Site 02; 🇧🇪 Jette, Belgium

Site 54; 🇨🇿 Brno, Czechia

Site 51; 🇨🇿 Prague, Czechia

Site 15; 🇩🇪 Bielefeld, Germany

Site 11; 🇩🇪 Bonn, Germany

Site 52; 🇨🇿 Usti Nad Labem, Czechia

Site 53; 🇨🇿 Prague, Czechia

Site 14; 🇩🇪 München, Germany

Site 12; 🇩🇪 Hannover, Germany

Site 13; 🇩🇪 Münster, Germany

Site 21; 🇵🇱 Warschau, Poland

Site 31; 🇪🇸 Barcelona, Spain

Site 32; 🇪🇸 Barcelona, Spain

Site 33; 🇪🇸 Barcelona, Spain

Site34; 🇪🇸 Barcelona, Spain

Site 41; 🇨🇭 Liestal, Switzerland

Site 43; 🇨🇭 Zürich, Switzerland

Site 71; 🇬🇧 Basingstoke, United Kingdom