AdFIrst - Adjusted Fibrinogen replacement strategy
Research type
Research Study
Full 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)
IRAS ID
285358
Contact name
Asoke Roy
Contact email
Sponsor organisation
Biotest AG
Eudract number
2017-001163-20
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 11 months, 11 days
Research summary
Research Summary
The purpose of the study is to investigate efficacy and safety of the fibrinogen concentrate BT524, when administered to patients with major blood loss during major spinal or abdominal surgery. The study aims to demonstrate that BT524 is at least not worse than the comparator fresh frozen plasma / cryoprecipitate in reducing intra-operative (during surgery) blood loss.
Fibrinogen is the first coagulation (clotting) factor to become critically reduced during intra-operative bleeding. Therefore, rapid fibrinogen supplementation to restore in the blood is an important component to achieve and maintain haemostasis (stopping the flow of blood) in bleeding patients. In this study patients with major blood loss during major spinal or abdominal surgery will be randomised 1:1 to a single intravenous (into the vein) transfusion of the fibrinogen concentrate BT524 or to fibrinogen-containing fresh frozen plasma /cryoprecipitate.
In the UK, this study will enrol both male and female participants, aged 18 and above undergoing elective abdominal (cytoreductive pseudomyxoma peritonei (PMP)) surgery with expected major blood loss. Screening for eligibility will occur during the 6 week period prior to surgery. Follow up will occur during the 5 weeks post-surgery.
Summary of Results
In a recent clinical study, researchers evaluated the efficacy and safety of BT524, a human fibrinogen concentrate, in managing severe bleeding in patients with acquired hypofibrinogenemia undergoing major surgeries on the spine or abdomen. Hypofibrinogenemia is a condition where the blood lacks enough fibrinogen, a crucial protein for blood clotting, which can lead to uncontrolled bleeding.
Study Design: The study was a multicenter, randomized, and controlled study involving 222 adult participants who underwent elective surgeries that carry high bleeding risks, either on the spine or for pseudomyxoma peritonei (PMP), a type of abdominal tumor. Participants were randomly assigned to receive either BT524 or the standard treatments, fresh frozen plasma (FFP) or cryoprecipitate, both commonly used to manage bleeding by replenishing clotting factors.
Key Findings: The main goal of the study was to determine if BT524 was as effective (non-inferior) as FFP/cryoprecipitate in reducing blood loss during surgery. Success was defined by a non-inferiority margin of 150 mL, meaning BT524 could be considered effective if it did not result in significantly more blood loss than the standard treatments. Results showed BT524 met this goal, with an average reduction in blood loss of 279 mL compared to standard therapy. This finding was statistically significant, indicating that BT524 is at least as effective as FFP/cryoprecipitate in controlling bleeding during surgery.
Additional analyses suggested that BT524 provided faster and more effective correction of fibrinogen levels. Maintaining adequate fibrinogen levels is crucial for effective blood clotting and minimizing further bleeding.
Safety Outcomes: BT524 showed a favorable safety profile, with side effects similar in nature and frequency to those of standard treatments. Most adverse effects were mild or moderate, with serious adverse events (SAEs) more common in the FFP/cryoprecipitate group. Importantly, BT524 was associated with fewer thromboembolic events (blood clots), which can be a risk with fibrinogen-related treatments. No deaths or significant complications were linked to BT524, affirming its safety as a supplementary treatment for managing bleeding in these surgical settings.
Implications: The results support BT524 as a safe and effective option for managing severe intra-operative bleeding due to acquired hypofibrinogenemia. This drug may be particularly useful for surgeries with high bleeding risks, such as abdominal and spinal surgeries, due to its rapid action in correcting fibrinogen levels and its favorable safety profile. These findings could broaden the treatment options available for surgical patients with bleeding complications associated with hypofibrinogenemia.
In conclusion, BT524 has shown potential as an effective alternative to traditional plasma products, offering comparable bleeding control with a faster and more sustained correction of fibrinogen levels, and with fewer side effects, including a lower risk of blood clots.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
20/WM/0222
Date of REC Opinion
17 Sep 2020
REC opinion
Further Information Favourable Opinion