Literature DB >> 27317703

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

N Rahe-Meyer1, J H Levy2, C D Mazer3, A Schramko4, A A Klein5, R Brat6, Y Okita7, Y Ueda8, D S Schmidt9, R Ranganath10, R Gill11.   

Abstract

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.
© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Entities:  

Keywords:  blood, coagulation; fibrinogen; haemorrhage; surgery, cardiovascular

Mesh:

Substances:

Year:  2016        PMID: 27317703      PMCID: PMC4913420          DOI: 10.1093/bja/aew169

Source DB:  PubMed          Journal:  Br J Anaesth        ISSN: 0007-0912            Impact factor:   9.166


  22 in total

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2.  Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery.

Authors:  C Solomon; U Pichlmaier; H Schoechl; C Hagl; K Raymondos; D Scheinichen; W Koppert; N Rahe-Meyer
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Review 3.  The effects of pre- and postoperative fibrinogen levels on blood loss after cardiac surgery: a systematic review and meta-analysis.

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Review 4.  Safety of fibrinogen concentrate: analysis of more than 27 years of pharmacovigilance data.

Authors:  C Solomon; A Gröner; J Ye; I Pendrak
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5.  Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates.

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6.  Thromboelastometry-guided administration of fibrinogen concentrate for the treatment of excessive intraoperative bleeding in thoracoabdominal aortic aneurysm surgery.

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7.  Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery: a prospective observational study.

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Review 8.  Adverse effects of plasma transfusion.

Authors:  Suchitra Pandey; Girish N Vyas
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9.  Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery.

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Review 10.  Cryoprecipitate therapy.

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6.  Why does a point of care guided transfusion algorithm not improve blood loss and transfusion practice in patients undergoing high-risk cardiac surgery? A prospective randomized controlled pilot study.

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7.  Correlation Between ROTEM FIBTEM Maximum Clot Firmness and Fibrinogen Levels in Pediatric Cardiac Surgery Patients.

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8.  Short-term recovery pattern of plasma fibrinogen after cardiac surgery: A prospective observational study.

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9.  A Low-dose human fibrinogen is not effective in decreasing postoperative bleeding and transfusion requirements during cardiac surgery in case of concomitant clinical bleeding and low FIBTEM values: A retrospective matched study.

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10.  Efficacy of fibrinogen concentrate in major abdominal surgery - A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei.

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Journal:  J Thromb Haemost       Date:  2019-11-26       Impact factor: 5.824

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