Early and Systematic Administration of Fibrinogen Concentrate in Postpartum Haemorrhage Following Vaginal Delivery: The FIDEL Randomized Controlled Trial

Authors : Ducloy Bouthors, AS; Mercier, FJ.; Grouin, JM; Bayoumeu, F; Corouge, J; Le Gouez, A; Rackelboom, T; Broisin, F; Vial, F; Luzi, A; Capronnier, O; Huissoud, C; Mignon, A.

Affiliations: Pole anesthésie réanimation, maternité Jeanne de Flandre, CHRU Lille, France ; ULR 7365 Université Lille, France; Hôpital Antoine Béclère, Assistance Publique Hôpitaux de Paris, Clamart, France ; Inserm U1219, Population Health, Bordeaux, France ; Hôpital Paule de Viguier, CHU Toulouse, Toulouse, France ; Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France ; Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France ; Maternité Adolphe Pinard, CHU de Nancy, Nancy, France ; CHU Sud. St Pierre-de-la-Réunion, France; Euraxi Pharma, France; INSERM U846, Stem Cell and Brain Research Institute, Bron, France.

Publication : BJOG ; March 2021

Abstract: OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN: Multicentre, double-blind, randomized placebo-controlled trial. SETTING: 30 French hospitals. POPULATION: patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS: Within 30 min after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES: Failure as composite primary efficacy endpoint: at least 4 g/dL of haemoglobin decrease and/or transfusion of at least 2 units of packed red blood cells within 48h following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures, and maternal morbidity-mortality within 6±2 weeks after delivery. RESULTS: 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346mL) and plasma fibrinogen (4.1 ± 0.9g/L) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the Fibrinogen and placebo groups, respectively (OR=0.99) after adjustment for centre and baseline plasma fibrinogen; (95%CI: [0.66;1.47]; p=0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/L in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group, versus two in the placebo group. CONCLUSIONS: As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs, and postpartum anaemia, but prevented plasma fibrinogen decrease without any subsequent thromboembolic events.