Clinical trial NCT03444324: Adjusted Fibrinogen Replacement Strategy
Official 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bleeding Disorder
Hypofibrinogenemia; Acquired
Keywords: Fibrinogen
Lead sponsor: Biotest
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
name: ICON Clinical Research
First posted: 2018-02-23
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were randomly assigned to treatment with BT524 or FFP/Cryo.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intra-operative Blood Loss
timeFrame: From decision to treat the subject with IMP until end of surgery, an average of 5 hours
Secondary outcomes:
measure: Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration
timeFrame: Prior first dose, 15 minutes after start of first IMP administration
measure: Time to First Successful Correction of Fibrinogen Level
timeFrame: prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery
measure: Transfusion Requirements: Cell Salvage
timeFrame: After start of first IMP administration until end of surgery, an average of 5 hours
measure: Transfusion Requirements: Allogeneic Platelets
timeFrame: After start of first IMP administration until end of surgery, an average of 5 hours
measure: Transfusion Requirements: Allogeneic Red Blood Cells
timeFrame: After start of first IMP administration until end of surgery, an average of 5 hours
measure: Transfusion Requirements: Fresh Frozen Plasma
timeFrame: After start of first IMP administration until end of surgery, an average of 5 hours
measure: Transfusion Requirements, Cryoprecipitate
timeFrame: After start of first IMP administration until end of surgery, an average of 5 hours
measure: Amount of Red Blood Cells (RBCs)
timeFrame: After start of first IMP administration until end of surgery, an average of 5 hours
measure: Post-operative Blood Loss
timeFrame: From end of surgery (time of last suture) up to 24 hours after the end of surgery
measure: Subjects With Rebleeds
timeFrame: End of surgery up to 8 days after surgery
measure: Hospital Length of Stay After Surgery
timeFrame: From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
measure: In-hospital Mortality
timeFrame: From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
measure: Number of Subjects With Thrombosis or Thromboembolic Events (TEEs)
timeFrame: From day of surgery until closing visit (up to 181 days)
measure: Change in Viral Status
timeFrame: Screening visit (up to 42 days prior to surgery) and closing visit (up to 181 days after surgery)
Other outcomes:
Locations:
city: Jette
country: Belgium
facility: Site 02
city: Leuven
country: Belgium
facility: Site 01
city: Brno
country: Czechia
facility: Site 54
city: Prague
country: Czechia
facility: Site 51
city: Prague
country: Czechia
facility: Site 53
city: Usti Nad Labem
country: Czechia
facility: Site 52
city: Bielefeld
country: Germany
facility: Site 15
city: Bonn
country: Germany
facility: Site 11
city: Hannover
country: Germany
facility: Site 12
city: München
country: Germany
facility: Site 14
city: Münster
country: Germany
facility: Site 13
city: Warschau
country: Poland
facility: Site 21
city: Barcelona
country: Spain
facility: Site 31
city: Barcelona
country: Spain
facility: Site 32
city: Barcelona
country: Spain
facility: Site 33
city: Barcelona
country: Spain
facility: Site34
city: Liestal
country: Switzerland
facility: Site 41
city: Zürich
country: Switzerland
facility: Site 43
city: Basingstoke
country: United Kingdom
facility: Site 71
Study officials:
affiliation: Franziskus Hospital, Bielefeld
name: Niels Rahe-Meyer, Prof.
role: PRINCIPAL_INVESTIGATOR
References: