All pregnant women who received prenatal care in the participating centres were given information about www.selleckchem.com/products/CP-690550.html this protocol during routine third-trimester visits. The women gave their written consent before entering the study in accordance with the Declaration of Helsinki. This study was funded and monitored by the French Ministry of Health (Programme Hospitalier National de Recherche Clinique, 2004 no. 1915). The funding source approved the study but had no role in the collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.Study design and patient eligibility criteriaThis academic multicentred, randomised, controlled, open-label study evaluated the efficacy and safety of TA in women with PPH.

The design of the study is presented Figure Figure1.1. In each participating centre, an under-buttocks drape with a graduated collection pouch (Vygon, Ecouen, France) was placed immediately after each vaginal delivery to measure blood loss in the postpartum period. Overestimation of blood loss because of the addition of antiseptic or saline solutions used for washing or bladder catheterization was avoided. Midwives unaware of the group allocation measured the volume of haemorrhage in the graduated collection bag at each time point. Gauze was strictly kept for weighing. Baseline and final blood loss measurement were quantified and verified by weighing the pouch and the gauze.

All patients with PPH >500 mL were managed according to the same timing according to French practice guidelines [16]: bladder catheter, manual removal of retained placenta, genital tract examination, uterine exploration and oxytocin (30 U/30 minutes), followed, and if these procedures were inefficacious, sulprostone was administered (500 ��g in 1 hour) without any procoagulant treatment. Patients with PPH >800 mL were included in the study. Exclusion criteria were age <18 years, absence of informed consent, caesarean section, presence of known haemostatic abnormalities before pregnancy and history of thrombosis or epilepsy.Figure 1Diagram showing the study design. PPH, postpartum haemorrhage; TXA, tranexamic acid.Immediately after inclusion, patients were randomised to receive either TA (TA group) or no antifibrinolytic treatment (control group). The randomisation sequence was generated by a centralized computer, and randomisation was balanced by centre.

In the TA group, a dose of 4 g of TA was mixed with 50 mL of normal saline and administered intravenously over a 1-hour period. After the loading dose infusion, a maintenance infusion of 1 g/hour was initiated and maintained for 6 hours. This high dose was chosen as the best GSK-3 dose for the reduction of bleeding in high-risk cardiac surgery [17,18] and was administered to reduce significant active haemorrhage of more than 800 mL the clinical course of which might be life-threatening.