TY - JOUR
T1 - Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery
T2 - A randomized, placebo-controlled, multicenter clinical trial
AU - Karkouti, Keyvan
AU - Von Heymann, Christian
AU - Jespersen, Christian M.
AU - Korte, Wolfgang
AU - Levy, Jerrold H.
AU - Ranucci, Marco
AU - Sellke, Frank W.
AU - Song, Howard K.
N1 - Funding Information:
The trial was sponsored by Novo Nordisk A/S (Bagsværd, Denmark) . Dr Karkouti is supported in part by a merit award from the Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada .
Funding Information:
The trial was sponsored by Novo Nordisk A/S (Bagsværd, Denmark). The authors designed the trial protocol, directed the statistical plan, and wrote the manuscript. The sponsor oversaw the trial operations, audited all data, and conducted the statistical analyses. Dr Karkouti signed the clinical trial report, and the authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree with the manuscript as written.
PY - 2013/10
Y1 - 2013/10
N2 - 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).
AB - 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).
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U2 - 10.1016/j.jtcvs.2013.04.044
DO - 10.1016/j.jtcvs.2013.04.044
M3 - Article
C2 - 23820174
AN - SCOPUS:84884418748
SN - 0022-5223
VL - 146
SP - 927
EP - 939
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 4
ER -