Trial Of Pathogen-reduced Cryoprecipitate vs. Cryoprecipitated AHF to Lower Operative Transfusions (TOP-CLOT): study protocol for a single center, prospective, cluster randomized trial

Background: Intraoperative hemorrhage in cardiac surgery increases risk of morbidity and mortality. Low pre-operative and perioperative levels of fibrinogen, a key clotting factor, are associated with severity of hemorrhage and increased transfusion of blood components. The ability to supplement fibrinogen during hemorrhagic resuscitation is delayed 45-60 min because cryoprecipitated antihemophilic factor (cryo AHF) is stored frozen, due to a short post-thaw shelf life. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) can be kept thawed, at room temperature, for up to 5 days, making it possible to be immediately available for hemorrhaging patients. This trial will investigate if earlier correction of acquired hypofibrinogenemia with IFC in hemorrhaging cardiac surgery patients reduces the total number of perioperatively transfused allogeneic blood products (red blood cells, plasma, and platelets) as compared to cryo AHF.

Methods: This is a single center, prospective, cluster randomized trial with an adaptive design. Acquired hypofibrinogenemia will be assessed by rotational thromboelastometry (ROTEM) and the threshold for cryo AHF/IFC transfusion defined as FIBTEM A10 ≤ 10 mm in bleeding patients. IFC/cryo AHF will be randomized by 1-month blocks. Cardiac surgery patients will be enrolled in the study if they have an eligible procedure and at least one dose of a cryo AHF/IFC product (approximately 2 g fibrinogen) is transfused. Data from the electronic health record, including the blood bank and lab information systems, will be prospectively collected from the health system's data warehouse.

Discussion: This trial aims to provide evidence of the clinical efficacy of utilizing readily available thawed IFC during acute bleeding in the cardiac surgery setting compared to traditional cryo AHF.

Trial registration: ClinicalTrials.gov NCT05711524. Feb 3, 2023.