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Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.

Publication ,  Journal Article
Rahe-Meyer, N; Levy, JH; Mazer, CD; Schramko, A; Klein, AA; Brat, R; Okita, Y; Ueda, Y; Schmidt, DS; Ranganath, R; Gill, R
Published in: Br J Anaesth
July 2016

BACKGROUND: Single-dose human fibrinogen concentrate (FCH) might have haemostatic benefits in complex cardiovascular surgery. METHODS: Patients undergoing elective aortic surgery requiring cardiopulmonary bypass were randomly assigned to receive FCH or placebo. Study medication was administered to patients with a 5 min bleeding mass of 60-250 g after separation from bypass and surgical haemostasis. A standardized algorithm for allogeneic blood product transfusion was followed if bleeding continued after study medication. RESULTS: 519 patients from 34 centres were randomized, of whom 152 (29%) met inclusion criteria for study medication. Median (IQR) pretreatment 5 min bleeding mass was 107 (76-138) and 91 (71-112) g in the FCH and placebo groups, respectively (P=0.13). More allogeneic blood product units were administered during the first 24 h after FCH, 5.0 (2.0-11.0), when compared with placebo, 3.0 (0.0-7.0), P=0.026. Fewer patients avoided transfusion in the FCH group (15.4%) compared with placebo (28.4%), P=0.047. The FCH immediately increased plasma fibrinogen concentration and fibrin-based clot strength. Adverse event rates were comparable in each group. CONCLUSIONS: Human fibrinogen concentrate was associated with increased allogeneic blood product transfusion, an unexpected finding contrary to previous studies. Human fibrinogen concentrate may not be effective in this setting when administered according to 5-minute bleeding mass. Low bleeding rates and normal-range plasma fibrinogen concentrations before study medication, and variability in adherence to the complex transfusion algorithm, may have contributed to these results. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier no. NCT01475669; EudraCT trial no. 2011-002685-20.

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Published In

Br J Anaesth

DOI

EISSN

1471-6771

Publication Date

July 2016

Volume

117

Issue

1

Start / End Page

41 / 51

Location

England

Related Subject Headings

  • Young Adult
  • Middle Aged
  • Male
  • Humans
  • Hemostatics
  • Hemostasis, Surgical
  • Hemorrhage
  • Fibrinogen
  • Female
  • Double-Blind Method
 

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Rahe-Meyer, N., Levy, J. H., Mazer, C. D., Schramko, A., Klein, A. A., Brat, R., … Gill, R. (2016). Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy. Br J Anaesth, 117(1), 41–51. https://doi.org/10.1093/bja/aew169
Rahe-Meyer, N., J. H. Levy, C. D. Mazer, A. Schramko, A. A. Klein, R. Brat, Y. Okita, et al. “Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.Br J Anaesth 117, no. 1 (July 2016): 41–51. https://doi.org/10.1093/bja/aew169.
Rahe-Meyer N, Levy JH, Mazer CD, Schramko A, Klein AA, Brat R, et al. Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy. Br J Anaesth. 2016 Jul;117(1):41–51.
Rahe-Meyer, N., et al. “Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.Br J Anaesth, vol. 117, no. 1, July 2016, pp. 41–51. Pubmed, doi:10.1093/bja/aew169.
Rahe-Meyer N, Levy JH, Mazer CD, Schramko A, Klein AA, Brat R, Okita Y, Ueda Y, Schmidt DS, Ranganath R, Gill R. Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy. Br J Anaesth. 2016 Jul;117(1):41–51.
Journal cover image

Published In

Br J Anaesth

DOI

EISSN

1471-6771

Publication Date

July 2016

Volume

117

Issue

1

Start / End Page

41 / 51

Location

England

Related Subject Headings

  • Young Adult
  • Middle Aged
  • Male
  • Humans
  • Hemostatics
  • Hemostasis, Surgical
  • Hemorrhage
  • Fibrinogen
  • Female
  • Double-Blind Method