Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial

BACKGROUND Postpartum haemorrhage (PPH) is a major cause of maternal morbidity. Bleeding is caused by a combination of physical causes, such as failure of the uterus to contract or operations, and is made worse by impairment of the blood clotting system. A number of studies have shown that low levels of the blood clotting factor fibrinogen are associated with progression of bleeding, the need for invasive interventions and transfusions of red blood cells and fresh frozen plasma (FFP). This trial will investigate whether early infusion of fibrinogen concentrate during a major PPH, with the aim of correcting a low fibrinogen to a level that is normal for delivery, based on the Fibtem test, reduces the total number of allogeneic blood products (red blood cells, FFP, cryoprecipitate and platelets) transfused after study medication until discharge, compared to placebo. METHODS/DESIGN This is a prospective, randomised, double-blind placebo controlled trial. Women will enter an observational phase and if their Fibtem levels fall they will be randomised in the interventional phase. A total of 60 women will be randomised and women are eligible for the trial if they meet all of the following inclusion criteria: age 18 years or over, gestation ≥24 + 0 weeks, haemorrhage of about 1500 ml and on-going bleeding without another complication or haemorrhage of about 1000 ml and caesarean section/uterine atony/placental abruption/placenta praevia/cardiovascular instability or microvascular oozing. Participants with a Fibtem A5 < 16 mm will be randomly allocated to receive either a bolus infusion of fibrinogen concentrate or placebo (isotonic saline). The dose of fibrinogen concentrate or placebo will be calculated based on the woman's ideal body weight for height and the measured Fibtem A5 with the aim of increasing the Fibtem A5 to 23 mm. DISCUSSION The trial aims to provide evidence on the efficacy and safety of fibrinogen concentrate during acute bleeding in an obstetric setting. TRIAL REGISTRATION ISRCTN ref: ISRCTN46295339 (01.07.2013); EudraCT: 2012-005511-11 (28.11.2012), UKCRN ref: 13940.