A clinical trial is currently underway at a quaternary care academic medical center in New York City to evaluate the effectiveness of INTERCEPT Fibrinogen Complex (IFC), a pathogen-reduced cryoprecipitate, compared to conventional cryoprecipitated antihemophilic factor (cryo AHF) in patients undergoing cardiothoracic surgery. The study aims to determine if using IFC can reduce the overall need for blood transfusions and improve other clinical outcomes.
Study Design and Objectives
The trial employs a single-center, prospective, cluster-randomized, non-blinded design with adaptive elements. Each month, all patients receiving cryoprecipitate during cardiac surgery will be treated with either IFC or cryo AHF, based on a predetermined randomization scheme. This cluster randomization approach is intended to enhance adherence to the protocol, minimize disruptions to blood bank operations, and prevent delays in patient care.
The primary outcome of the study is the total number of non-cryo AHF/IFC blood components (red blood cells, platelets, plasma) transfused during the patient's admission within the first 30 days following surgery. Secondary outcomes include the number of cryo AHF/IFC or fibrinogen concentrate products used perioperatively, the time from order to transfusion, the number of cryo AHF/IFC units wasted, laboratory measures related to fibrinogen supplementation, volume of chest tube drainage, length of stay in the operating room, ICU, and hospital, need for postoperative ventilator therapy, and overall cost analysis.
Inclusion and Exclusion Criteria
Patients eligible for the study are adults (over 18 years) undergoing cardiovascular surgery who receive intraoperative cryo AHF/IFC during the study period. Cardiovascular surgeries include coronary artery bypass grafting, valve repair or replacement, open thoracic aortic and thoracoabdominal aortic surgery, atrial or ventricular septal defects, and ventricular assist device implantation or revision.
Exclusion criteria include pregnant women, pediatric patients, cardiac transplant recipients, patients transferred after surgery from other hospitals, patients with known coagulopathies or congenital dysfibrinogenemia or afibrinogenemia, and patients who do not receive cryo AHF/IFC in the operating room during the primary procedure.
Interventions and Randomization
Both IFC and cryo AHF are considered clinically equivalent products by the investigators. Cryo AHF is a plasma-derived product from five blood donors and is the conventional method for fibrinogen replacement in the United States. IFC is also plasma-derived but undergoes pathogen reduction using the INTERCEPT Blood System, which inactivates potential pathogens and residual lymphocytes.
Randomization is conducted monthly, with the blood bank staff notified each month regarding which product to use. During IFC months, four doses of thawed IFC20 are readily available. Goal-directed therapy with viscoelastic testing (ROTEM) guides component transfusion decisions, with FIBTEM A10 used to assess fibrinogen levels.
Data Collection and Statistical Analysis
Data will be collected prospectively from the electronic health record, blood bank, and lab information systems. Automated SQL queries will extract data, which will then be stored in a Microsoft SQL database and imported into REDCap. Statistical analysis will include a two-sample t-test on log-transformed values for the primary outcome. The Wilcoxon rank-sum test will be used for secondary endpoints. An interim analysis for futility will be conducted when approximately 60% of the subjects have completed the trial.
Potential Benefits and Implications
This trial addresses the need for improved strategies in managing bleeding during cardiac surgery. By comparing IFC and cryo AHF, the study aims to provide evidence on whether pathogen reduction can lead to reduced transfusion needs, shorter hospital stays, and decreased healthcare costs. The results of this trial could influence transfusion practices and resource allocation in cardiac surgery, potentially benefiting both patients and healthcare systems.
