Factor VIII inhibitor bypass activity (FEIBA) for the reduction of transfusion in cardiac surgery: a randomized, double-blind, placebo-controlled, pilot trial
Pilot and feasibility studies. 2021;7(1):137
BACKGROUND Uncontrolled bleeding after cardiac surgery can be life-threatening. Factor eight inhibitor bypassing activity (FEIBA) is a prothrombin complex concentrate empirically used as rescue therapy for correction of refractory bleeding diathesis post-cardiopulmonary bypass (CPB). FEIBA used as rescue therapy for bleeding diathesis after CPB has been associated with a low incidence of complications and a reduction in transfusion requirement and re-exploration. The feasibility and efficacy of early administration of FEIBA after the termination of CPB have not been studied in a prospective randomized trial. METHODS We designed a small randomized, double-blinded, placebo-controlled pilot trial to determine the feasibility of a larger trial testing the hypothesis that FEIBA decreases transfusion requirements after CPB. The study was designed to evaluate the feasibility of a larger pivotal trial to determine the effectiveness of FEIBA in reducing the total volume of blood products transfused perioperatively, and its safety profile. Study participants were adult patients undergoing elective major aortic cardiovascular surgery at a tertiary referral hospital, who were equally randomized to receive a single dose of either FEIBA or matched placebo intraoperatively at the end of CPB. RESULTS Twenty patients were screened and 12 were randomized and included in the analysis. Protocol adherence was high, and all patients received the study drug per intention-to-treat except one patient. There were no protocol deviations or events of unblinding, and adverse events were not different between groups. Patients in the FEIBA group were older and more likely to be female and had higher BMI, lower hematocrit, and longer hypothermic circulatory arrest. There were no differences in post-randomization blood product transfusions (difference FEIBA vs. placebo -899 mL; 95% CI -5206 to 3409) or in the administration of open-label FEIBA. CONCLUSIONS This pilot trial confirmed the adequacy of the trial design that involved the early, blinded administration of FEIBA, by demonstrating excellent protocol adherence. We conclude that a larger trial establishing the effectiveness of early prothrombin complex concentrate administration to reduce the use of blood products in the setting of high-risk cardiac surgery is feasible. TRIAL REGISTRATION ClinicalTrials.gov, NCT02577614 . Registered 16 October 2015.
Safe application of a restrictive transfusion protocol in moderate-risk patients undergoing cardiac operations
Annals of Thoracic Surgery. 2014;97((5):):1630-5.
BACKGROUND Perioperative red blood cell transfusion is associated with adverse outcomes after cardiac operations. Although restrictive transfusion protocols have been developed, their safety and efficacy are not well demonstrated, and considerable variation in transfusion practice persists. We report our experience with a restrictive transfusion protocol. METHODS We analyzed the outcomes in 409 patients undergoing cardiac operations enrolled in a trial conducted at 30 centers worldwide. Blood products were administered on the basis of a transfusion algorithm applied across all centers, with a restrictive transfusion trigger of hemoglobin less than or equal to 6 g/dL. Transfusion was acceptable but not mandatory for hemoglobin 6 to 8 g/dL. For hemoglobin 8 to 10 g/dL, transfusion was acceptable only with evidence for end-organ ischemia. RESULTS The patient population was moderately complex, with 20.5% having combined procedures and 29.6% having nonelective operations. The mean EuroSCORE for the population was 4.3, which predicted a substantial incidence of morbidity and mortality. Actual outcomes were excellent, with observed mortality of 0.49% and rates of cerebrovascular accident, myocardial infarction, and acute renal failure 1.2%, 6.1%, and 0.98%, respectively. The frequency of red blood cell transfusion was 33.7%, which varied significantly by center. Most transfusions (71.9%) were administered for hemoglobin 6 to 8 g/dL; 21.4% were administered for hemoglobin 8 to 10 g/dL with evidence for end-organ ischemia; 65.0% of patients avoided allogeneic transfusion altogether. CONCLUSIONS A restrictive transfusion protocol can be safely applied in the care of moderate-risk patients undergoing cardiac operations. This strategy has significant potential to reduce transfusion and resource utilization in these patients, standardize transfusion practices across institutions, and increase the safety of cardiac operations. Copyright 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery: A randomized, placebo-controlled, multicenter clinical trial
Journal of Thoracic & Cardiovascular Surgery. 2013;146((4):):927-39.
OBJECTIVES Cardiac surgery with cardiopulmonary bypass frequently leads to excessive bleeding, obligating blood product transfusions. Because low factor XIII (FXIII) levels have been associated with bleeding after cardiac surgery, we investigated whether administering recombinant FXIII after cardiopulmonary bypass would reduce transfusions. METHODS In this double-blinded, placebo-controlled, multicenter trial, 409 cardiac surgical patients at moderate risk for transfusion were randomized to receive an intravenous dose of recombinant FXIII, 17.5 IU/kg (n=143), 35 IU/kg (n=138), or placebo (n=128) after cardiopulmonary bypass. Transfusion guidelines were standardized. The primary efficacy outcome was avoidance of allogeneic blood products for 7 days postsurgery. Secondary outcomes included amount of blood products transfused and reoperation rate. Serious adverse events were measured for 7 weeks. RESULTS Study groups had comparable baseline characteristics and an approximately 40% decrease in FXIII levels after cardiopulmonary bypass. Thirty minutes postdose, FXIII levels were restored to higher than the lower 2.5th percentile of preoperative activity in 49% of the placebo group, and 85% and 95% of the 17.5- and 35-IU/kg recombinant FXIII groups, respectively (P<.05 for both treatments vs placebo). Transfusion avoidance rates were 64.8%, 64.3%, and 65.9% with placebo, 17.5 IU/kg, and 35 IU/kg recombinant FXIII (respective odds ratios against placebo, 1.05 [95% confidence interval, 0.61-1.80] and 0.99 [95% confidence interval, 0.57-1.72]). Groups had comparable adverse event rates. CONCLUSIONS Replenishment of FXIII levels after cardiopulmonary bypass had no effect on transfusion avoidance, transfusion requirements, or reoperation in moderate-risk cardiac surgery patients (ClinicalTrials.gov identifier: NCT00914589). Copyright 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.