Background and Goal of Study: Coagulopathic bleeding is a serious complication of cardiac surgery. A key contributor is acquired hypofibrinogenaemia (plasma fibrinogen <1.5–2.0 g/L), the standard treatment for which is cryoprecipitate. Purified fibrinogen concentrate is also used, but few comparative data exist and randomised trials are needed. The primary objective of the FIBrinogen REplenishment in Surgery (FIBRES) study is to demonstrate that a new fibrinogen concentrate (Octafibrin/Fibryga, Octapharma) is non-inferior to cryoprecipitate.
Materials and Methods: This is a pragmatic, multi-centre, active-control, randomised (1:1), single-blinded, non-inferiority, phase 3 trial in adult cardiac surgical patients with clinically significant bleeding due to acquired hypofibrinogenaemia. Patients undergoing cardiopulmonary bypass (CPB) for whom fibrinogen supplementation is ordered within 24 hours will be randomised to receive 4 g fibrinogen concentrate or 10 units cryoprecipitate (dose equivalent). All randomised patients will receive fibrinogen supplementation according to clinical need. Patient consent at randomisation is waived, with written informed consent obtained after. Primary outcome is total red cell, platelet and plasma transfusions within 24 hours of CPB. Secondary outcomes include blood products used within 7 days, major bleeding within 24 hours, fibrinogen levels and adverse events. Enrolment of 1,200 patients will provide >90% power to demonstrate non-inferiority, based on a 20% non-inferiority margin, ≥550 patients/group and ~10% drop-out rate. An interim analysis includes 600 patients. The pragmatic design and treatment algorithm align with standard practice, aiding adherence and generalizability.
Results and Discussion: This is the largest randomised study of fibrinogen concentrate versus cryoprecipitate in adult cardiac surgical patients. Expected completion is late 2018, with results available in early 2019.
Conclusion(s): Non-inferiority of the new fibrinogen concentrate would support its use in cardiac surgical patients experiencing significant bleeding because of acquired hypofibrinogenaemia, an under-studied yet high-risk population.

09 / The FIBRES study: a pragmatic, randomised, active-control, non-inferiority, phase 3 trial comparing a new fibrinogen concentrate vs. cryoprecipitate for the treatment of acquired hypofibrinogenaemia in bleeding cardiac surgical patients