title: The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trial.
abstract: BACKGROUND
  Severe haemorrhage is a leading cause of maternal death worldwide. Most haemorrhage deaths occur soon after childbirth. Severe post-partum bleeding is sometimes managed by the surgical removal of the uterus (hysterectomy). Death and hysterectomy are important health consequences of post-partum haemorrhage, and clinical trials of interventions aimed at preventing these outcomes are needed.
  
  
  METHODS
  The World Maternal Antifibrinolytic trial aims to determine the effect of tranexamic acid on death, hysterectomy and other health outcomes in women with post-partum haemorrhage. It is an international, multicentre, randomised trial. Approximately 20,000 women with post-partum haemorrhage will be randomly allocated to receive an intravenous injection of either tranexamic acid or matching placebo in addition to usual care. The primary outcome measure is a composite of death in hospital or hysterectomy within 42 days of delivery. The cause of death will be described. Secondary outcomes include death, death due to bleeding, hysterectomy, thromboembolic events, blood transfusion, surgical and radiological interventions, complications, adverse events and quality of life. The health status and occurrence of thromboembolic events in breastfed babies will also be reported. We will conduct subgroup analyses for the primary outcome by time to treatment, type of delivery and cause of haemorrhage. We will conduct an analysis of treatment effect adjusted for baseline risk.
  
  
  CONCLUSIONS
  The World Maternal Antifibrinolytic trial should provide reliable evidence for the efficacy of tranexamic acid in the prevention of death, hysterectomy and other outcomes that are important to patients. We present a protocol update and the statistical analysis plan for the trial.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN76912190 (Registration date 08 December 2008), Clinicaltrials.gov NCT00872469 (Registration date 30 March 2009) and Pan African Clinical Trials Registry: PACTR201007000192283 (Registration date 02 September 2010).
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.affiliation: Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.affiliation: Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Edwards
authors.affiliation: Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Elbourne
authors.affiliation: Division of Perinatal and Reproductive Medicine, University of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool, L8 7SS, UK.
authors.forename: Zarko
authors.initials: Z
authors.lastname: Alfirevic
authors.affiliation: Infectious Diseases Epidemiology Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
authors.forename: Carine
authors.initials: C
authors.lastname: Ronsmans
mesh_terms: D000293:Adolescent; D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects / Q000401:mortality / Q000706:statistics & numerical data*; D007275:Injections, Intravenous; D008428:Maternal Mortality; D015233:Models, Statistical; D006473:Postpartum Hemorrhage / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D011247:Pregnancy; D012107:Research Design / Q000706:statistics & numerical data*; D012307:Risk Factors; D013997:Time Factors; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid
keywords: Clinical trial; Post-partum haemorrhage; Statistical analysis plan; Tranexamic acid