1.
Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery: A randomized, placebo-controlled, multicenter clinical trial
Karkouti K, von Heymann C, Jespersen CM, Korte W, Levy JH, Ranucci M, Sellke FW, Song HK
Journal of Thoracic & Cardiovascular Surgery. 2013;146((4):):927-39.
Abstract
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.
2.
Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery
Gill R, Herbertson M, Vuylsteke A, Olsen PS, von Heymann C, Mythen M, Sellke F, Booth F, Schmidt TA
Circulation. 2009;120((1):):21-7.
Abstract
BACKGROUND Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery. METHODS AND RESULTS In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0. 25; 80 microg/kg, 12%; P=0. 43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0. 03) or required allogeneic transfusions (P=0. 01). CONCLUSIONS On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.
3.
Recombinant activated factor VIIa for the treatment of bleeding in major abdominal surgery including vascular and urological surgery: a review and meta-analysis of published data
von Heymann C, Jonas S, Spies C, Wernecke KD, Ziemer S, Janssen D, Koscielny J
Critical Care. 2008;12((1):):R14.
Abstract
BACKGROUND The purpose of this study was to determine the role of recombinant activated factor VII (rFVIIa) in abdominal, vascular, and urological surgery. METHODS We conducted meta-analyses of case series and placebo-controlled studies reporting on the treatment or prophylaxis of bleeding with rFVIIa regarding 'reduction or cessation of bleeding', 'mortality', and 'thromboembolism'. RESULTS All case reports (n = 15 case reports and 17 patients) documented an effect of rFVIIa in the treatment of bleeding. A meta-analysis of 10 case series revealed a reduction or cessation of bleeding in 39 out of 50 patients after administration of rFVIIa (estimated mean effect 73.2%, 95% confidence interval [CI] 51.0% to 95.4%) and a mean probability of survival of 53.0% (95% CI 26.4% to 79.7%). Among the rFVIIa responders, 19 out of 29 patients (66%) survived versus 1 out of 10 rFVIIa nonresponders (P = 0.003). Six out of 36 patients from the case series had a thromboembolic complication (estimated mean probability 16.5%, 95% CI 1.2% to 31.8%). Compared with a meta-analysis of eight placebo-controlled studies, no increased risk of thromboembolism was seen after administration of rFVIIa. CONCLUSION The meta-analysis of case series showed that, in a mean of 73% patients, rFVIIa achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa. rFVIIa was not associated with an increased risk of thromboembolism compared with placebo.