title: The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial.
abstract: BACKGROUND
  Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage.
  
  
  METHODS
  The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose. The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy.
authors.affiliation: Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. haleema.shakur@lshtm.ac.uk
authors.forename: Haleema
authors.initials: H
authors.lastname: Shakur
authors.forename: Diana
authors.initials: D
authors.lastname: Elbourne
authors.forename: Metin
authors.initials: M
authors.lastname: Gülmezoglu
authors.forename: Zarko
authors.initials: Z
authors.lastname: Alfirevic
authors.forename: Carine
authors.initials: C
authors.lastname: Ronsmans
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Allen
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001942:Breast Feeding; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007044:Hysterectomy; D007275:Injections, Intravenous; D007391:International Cooperation; D015990:Placebo Effect; D006473:Postpartum Hemorrhage / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000601:surgery; D011247:Pregnancy; D012107:Research Design; D013997:Time Factors; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid
references.citation: Obstet Gynecol. 1999 Oct;94(4):595-9
references.pmid: 10511366
references.citation: Lancet. 2006 Sep 30;368(9542):1189-200
references.pmid: 17011946
references.citation: Lancet. 2005 Feb 19-25;365(9460):711-22
references.pmid: 15721478
references.citation: Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001886
references.pmid: 17943760
references.citation: Br J Cancer. 1977 Jan;35(1):1-39
references.pmid: 831755
references.citation: Br J Radiol. 1971 Oct;44(526):793-7
references.pmid: 4940475
references.citation: Int J Gynaecol Obstet. 2006 Sep;94(3):243-53
references.pmid: 16842791
references.citation: Lancet. 1993 Oct 9;342(8876):891-4
references.pmid: 8105166
references.citation: J Clin Pathol Suppl (R Coll Pathol). 1980;14:35-40
references.pmid: 6159375
references.citation: Br J Obstet Gynaecol. 1997 Mar;104(3):278-84
references.pmid: 9091002
references.citation: Ann Intern Med. 2005 Nov 15;143(10):697-706
references.pmid: 16287790
references.citation: Drugs. 1999 Jun;57(6):1005-32
references.pmid: 10400410
references.citation: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2005 Jul;25(7):658-61
references.pmid: 16089150
references.citation: Obstet Gynecol. 1999 Nov;94(5 Pt 1):730-4
references.pmid: 10546719
references.citation: Mymensingh Med J. 2005 Jan;14(1):95-119
references.pmid: 15695967
references.citation: Womens Health Issues. 2009 Jan-Feb;19(1):14-20
references.pmid: 19111783
references.citation: J Clin Pathol Suppl (R Coll Pathol). 1980;14:55-9
references.pmid: 7000848
references.citation: Semin Thromb Hemost. 2003 Apr;29(2):125-30
references.pmid: 12709915
references.citation: BMC Pregnancy Childbirth. 2009 Jul 15;9:29
references.pmid: 19604358
references.citation: BMJ. 1998 Oct 31;317(7167):1170-1
references.pmid: 9794846
references.citation: Br Med Bull. 2003;67:1-11
references.pmid: 14711750
references.citation: Anesthesiology. 1995 Feb;82(2):383-92
references.pmid: 7856897
references.citation: Lancet. 2006 Apr 1;367(9516):1066-1074
references.pmid: 16581405
references.citation: N Engl J Med. 1996 Jul 11;335(2):108-14
references.pmid: 8649471