The effect of tranexamic acid on the risk of death and hysterectomy in women with post-partum haemorrhage: statistical analysis plan for the WOMAN trialReport as inadecuate

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 - Download this document for free, or read online. Document in PDF available to download.


, 17:249

First Online: 17 May 2016Received: 29 September 2015Accepted: 06 April 2016DOI: 10.1186-s13063-016-1332-2

Cite this article as: Shakur, H., Roberts, I., Edwards, P. et al. Trials 2016 17: 249. doi:10.1186-s13063-016-1332-2


BackgroundSevere 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.

MethodsThe 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.

DiscussionThe 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.

Trial registrationCurrent Controlled Trials ISRCTN76912190 Registration date 08 December 2008, NCT00872469 Registration date 30 March 2009 and Pan African Clinical Trials Registry: PACTR201007000192283 Registration date 02 September 2010.

KeywordsPost-partum haemorrhage Tranexamic acid Clinical trial Statistical analysis plan AbbreviationsAEadverse event

CIconfidence interval

CONSORTConsolidated Standards of Reporting Trials

CRASH-2 trialClinical Randomisation of an Antifibrinolytic in Significant Haemorrhage Trial

CTUclinical trials unit

DICdisseminated intravascular coagulation

DMCdata monitoring committee

DVTdeep vein thrombosis

ICH-GCPInternational Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use – Good Clinical Practice

ICUintensive care unit

ITTintention to treat

MySQLMy Structured Query Language

PAIplasminogen activator inhibitors

PEpulmonary embolism

PHPPPH hypertext preprocessor

PPHpost-partum haemorrhage

SAEserious adverse event

SUSARsuspected unexpected serious adverse reaction

SDstandard deviation

TEthromboembolic events

TPAtissue plasminogen activator

TXAtranexamic acid

UKUnited Kingdom

RRrelative risk

VTEvenous thromboembolic event

WOMANWorld Maternal Antifibrinolytic Trial

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Electronic supplementary materialThe online version of this article doi:10.1186-s13063-016-1332-2 contains supplementary material, which is available to authorized users.

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Author: Haleema Shakur - Ian Roberts - Philip Edwards - Diana Elbourne - Zarko Alfirevic - Carine Ronsmans


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