A J Wikkelsø1, H M Edwards2, A Afshari3, J Stensballe4, J Langhoff-Roos5, C Albrechtsen3, K Ekelund3, G Hanke3, E L Secher3, H F Sharif5, L M Pedersen6, A Troelstrup6, J Lauenborg7, A U Mitchell8, L Fuhrmann8, J Svare2, M G Madsen9, B Bødker10, A M Møller8. 1. Department of Anaesthesia and Intensive Care Medicine, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark wikkelso@gmail.com. 2. Department of Obstetrics and Gynaecology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark. 3. Department of Anaesthesia, Mother and Child Section, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark. 4. Department of Anaesthesia, Centre of Head and Orthopaedics, and Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark. 5. Department of Obstetrics, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark. 6. Department of Anaesthesia and Intensive Care Medicine, Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, DK-2650, Denmark. 7. Department of Obstetrics and Gynaecology, Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, DK-2650, Denmark. 8. Department of Anaesthesia and Intensive Care Medicine, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark. 9. Department of Anaesthesia and Intensive Care Medicine, Hillerød Hospital, University of Copenhagen, Dyrehavevej 29, Hillerød DK-3400, Denmark. 10. Department of Obstetrics and Gynaecology, Hillerød Hospital, University of Copenhagen, Dyrehavevej 29, Hillerød DK-3400, Denmark.
Abstract
BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose offibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
RCT Entities:
BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
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