Elective spinal or abdominal surgery with expected major blood loss MedDRA version: 20.0 Level: PT Classification code 10051125 Term: Hypofibrinogenaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Human Fibrinogen Concentrate
Product Code: BT524
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: Human fibrinogen concentrate
CAS Number: 9001-32-5
Sponsors
Biotest AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At screening: 1.Written informed consent 2.Subjects scheduled for elective major spinal 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* 5. Intra-operative tigger for treatment a. Subjects undergoing spinal surgery: Intra-operative clinically relevant bleeding of approximately 1 L, requiring hemostatic treatment during surgery** b. Subjects undergoing cytoreductive PMP surgery: Intra-operative prediction of clinically relevant bleeding of >2 L, requiring hemostatic treatment during surgery*** *Inclusion criterion no. 4 aims to ensure that only subjects without hereditary bleeding disorders are to be included in this study. Subjects with continuous ‘aspirin intake’, subjects under Direct Oral Anti-Coagulants (DOACs), or with a hepatic disease are at higher bleeding risk. Nevertheless, these subjects can be included at the discretion of the investigator. **A clinically relevant bleeding, resulting in a high risk for the need of fibrinogen supplementation with BT524 or FFP during surgery. The amount of clinically relevant blood loss depends on the subject's clinical condition, e.g. underlying disease, significant comorbidities, low body weight, relevant change of a laboratory value. ***Only applicable for subjects in the UK Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
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 BT524 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main purpose of this phase III study is to demonstrate the efficacy of BT524 as a complementary therapy to management of uncontrolled severe hemorrhage in subjects undergoing elective major spinal or abdominal surgery. The primary objective of this study is to demonstrate that BT524 is therapeutically equivalent that means not worse than fresh frozen plasma (FFP) /cryoprecipitate with a non-inferiority margin of 150 mL in reducing intra-operative blood loss by intravenous (IV) administration in subjects with acquired hypofibrinogenaemia undergoing elective major spinal or abdominal surgery. If therapeutic equivalence has been demonstrated, therapeutic superiority of BT524 compared with FFP/cryoprecipitate will also be assessed. ;Secondary Objective: Secondary objectives are to demonstrate the efficacy of BT524 by assessing the correction of the fibrinogen level intra-operatively, the transfusion requirements, post-operative blood loss in the first 24 hours, the number of subjects with rebleeds, the hospital length of stay and the in-hospital mortality. Secondary objectives also comprise the safety of BT524 by documenting the number of adverse events (AE) including changes in laboratory parameters, the virus status, and the frequency and severity of thrombosis and of thromboembolic events (TEEs).;Primary end point(s): Efficacy: Intra-operative blood loss after decision to treat the subject with IMP until the end of surgery as measured by amount of blood from the blood suction unit and amount of blood from surgical cloths and compresses. ;Timepoint(s) of evaluation of this end point: Intra-operative blood loss after decision to treat the subject with IMP until the end of surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Proportion (%) of subjects with successful correction of fibrinogen level 15 minutes after start of first IMP administration •Time to first successful correction of fibrinogen level •Total amount of transfusion products (allogenic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery •Amount of red blood cells (allogenic and autologous RBCs) infused after start of first IMP administration until end of surgery •post-operative blood loss in the first 24 hours •Proportion (%) of subjects with rebleeds after the end of surgery until Day 8 •Hospital length of stay after surgery •In-hospital mortality Safety;Timepoint(s) of evaluation of this end point: Until closing visit (up to 70 days) | — |
Countries
Belgium, Czech Republic, European Union, Germany, Spain, Switzerland, United Kingdom
Contacts
Public ContactCorporate Clinical Research
Biotest AG
Outcome results
None listed