Adjusted Fibrinogen Replacement Strategy

Bleeding Disorder Clinical Trial

— AdFIrst  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03444324
• Other study ID #: 995
• Secondary ID: 2017-001163-20
• Status: Completed
• Phase: Phase 3
• Start date: February 12, 2018
• Est. completion date: October 2, 2023

Study information

• Verified date: November 2023
• Source: Biotest
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate efficacy and safety of fibrinogen concentrate BT524, when administered to patients with major blood loss during elective spine surgery.The study aims to demonstrate that BT524 is at least not worse than the comparator fresh frozen plasma in reducing intra-operative blood loss.

Description:

Fibrinogen is the first coagulation factor to become critically reduced during intra-operative bleeding. Therefore, rapid fibrinogen supplementation to restore physiological plasma levels is an important component to achieve and maintain hemostasis in bleeding patients. In this study, patients with major blood loss during elective spine surgery will be randomized 1:1 to a single intravenous transfusion of the fibrinogen concentrate BT524 or to fibrinogen-containing fresh frozen plasma (FFP).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: October 2, 2023
• Est. primary completion date: September 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

At screening:

1. Written informed consent

2. Subjects scheduled for elective major spine 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. Intra-operative bleeding > 1,000 mL (total blood loss), resulting in a high risk for the need of FFP transfusion during surgery.

Exclusion Criteria:

1. Pregnancy or unreliable contraceptive measures or lactation period (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 -

Related Conditions & MeSH terms

• Bleeding Disorder
• Blood Coagulation Disorders
• Hemostatic Disorders
• Hypofibrinogenemia; Acquired

Intervention

Biological:
• BT524
BT524 is administered intravenously, patient specific dosage calculated based on body weight and fibrinogen level.
• FFP/Cryo
FFP/Cryo is administered intravenously; dosage according to local standards in mL per kg body weight.

Locations

Country	Name	City	State
Belgium	Site 02	Jette
Belgium	Site 01	Leuven
Czechia	Site 54	Brno
Czechia	Site 51	Prague
Czechia	Site 53	Prague
Czechia	Site 52	Usti Nad Labem
Germany	Site 15	Bielefeld
Germany	Site 11	Bonn
Germany	Site 12	Hannover
Germany	Site 14	München
Germany	Site 13	Münster
Poland	Site 21	Warschau
Spain	Site 31	Barcelona
Spain	Site 32	Barcelona
Spain	Site 33	Barcelona
Spain	Site34	Barcelona
Switzerland	Site 41	Liestal
Switzerland	Site 43	Zürich
United Kingdom	Site 71	Basingstoke

Sponsors (2)

Lead Sponsor	Collaborator
Biotest	PRA Health Sciences

Countries where clinical trial is conducted

Belgium,  Czechia,  Germany,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Decision to treat until end of surgery, expected average of 3 hours
Secondary	Correction of the fibrinogen level	Proportion (%) of subjects with successful correction of fibrinogen level	15 minutes after start of IMP administration
Secondary	Transfusion requirements	Total amount of transfusion products	After end of IMP administration until end of surgery, expected average of 2 hours
Secondary	24 hours post-operative blood loss	Drainage volume	1 day after surgery
Secondary	Subjects with rebleeds	Proportion (%) of subjects	8 days after surgery
Secondary	Hospital length of stay	Days in hospital after surgery	35 days after surgery
Secondary	In-Hospital mortality	Number of death during hospital stay	35 days after surgery
Secondary	Adverse events	Number of adverse events	35 days after surgery
Secondary	Virus status	Number of subjects with viral infection	35 days after surgery
Secondary	Thrombosis and of thromboembolic events	Frequency and severity	35 days after surgery