Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.
From the Haemostasis and Transfusion Committee
Published: 3 May 2016
Authors: N. Rahe-Meyer, J. H. Levy, C. D. Mazer, A. Schramko, A. A. Klein, R. Brat, Y. Okita, Y. Ueda, D. S. Schmidt, R. Ranganath, R. Gill
Title: Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy
Study description: This prospective randomized, placebo-controlled, double-blind study investigated the impact of fibrinogen supplementation depending on the 5 minute bleeding mass on haemostasis after cardiac surgery involving cardiopulmonary bypass.
Main Objective: Transfusion requirements within 24 hours.
- The authors described significantly higher requirements of allogeneic blood products within 24 hours after surgery (5 vs. 3 units, p=0.026) compared to the placebo group despite a mean fibrinogen concentrate dosage of 6.29 g in the study
- Avoidance of allogeneic blood transfusion was higher in the placebo group (28.4% vs. 15.4%, p=0.047).
- No difference in thromboembolic events or other safety endpoints was observed
- This study describes unexpected results compared to previous single centre studies on the use of fibrinogen concentrate to improve haemostasis after cardiac surgery. These results need to be interpreted with caution as a documented variability in clinical practice, a high rate of transfusion protocol violations (32%) and the lack of fibrinogen deficiency (mean fibrinogen before supplementation = 1.9 g/l) may have influenced the results and demonstrate the difficulties to generalize results from a single centre to a multi centre setting.
There remain questions to be answered:
- At what fibrinogen or MCF threshold levels is the supplementation of fibrinogen concentrate beneficial?
- What is the appropriate dose of Fibrinogen and how can it be determined?
- Is there is enough evidence from other papers to support the use of this product when it is not licensed for use in this setting?