Adjusted Fibrinogen Replacement Strategy

Biotest222 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

222

Conditions

Bleeding Disorder Hypofibrinogenemia; Acquired

Interventions

BT524BIOLOGICAL

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.

FFP/CryoBIOLOGICAL

FFP/Cryo was administered intravenously; dosage according to local standards. FFP, 15 mL per kg body weight (BW); Cryoprecipitate, fixed dose of 10 units.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (19)

Site 02

Jette, Belgium

Site 01

Leuven, Belgium

Site 54

Brno, Czechia

Outcomes

Primary Outcomes

Intra-operative Blood Loss

Intra-operative blood loss as measured by amount of blood from blood suction unit and amount of blood from surgical cloths and compresses.

Time frame: From decision to treat the subject with IMP until end of surgery, an average of 5 hours

Secondary Outcomes

Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 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 frame: Prior first dose, 15 minutes after start of first IMP administration

Time to First Successful Correction of Fibrinogen Level

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.

Time frame: prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery

Transfusion Requirements: Cell Salvage

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.

Time frame: After start of first IMP administration until end of surgery, an average of 5 hours

Transfusion Requirements: Allogeneic Platelets

Data from ClinicalTrials.gov

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