Condition category
Pregnancy and Childbirth
Date applied
08/12/2008
Date assigned
10/12/2008
Last edited
19/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.womantrial.lshtm.ac.uk/

Contact information

Type

Scientific

Primary contact

Ms Haleema Shakur

ORCID ID

Contact details

Department of Epidemiology and Population Health
London School of Hygiene and Tropical Medicine
Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)20 7299 4684
thewomantrial@lshtm.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00872469

Protocol/serial number

N/A

Study information

Scientific title

Tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind, placebo controlled trial

Acronym

WOMAN

Study hypothesis

The WOMAN trial will provide reliable evidence as to whether the antifibrinolytic agent tranexamic acid can reduce mortality, hysterectomy and other morbidities in women with clinician-diagnosed postpartum haemorrhage (PPH).

Added 22/03/2012:
The WOMAN-ETAC is a sub-study which is nested in a cohort of WOMAN trial participants and aims to evaluate the effect of tranexamic acid on markers of coagulation in a sample of WOMAN trial participants. Two hundred participants in the WOMAN Trial at one centre in Nigeria (University College Hospital, Ibadan) will have venous blood taken after randomisation and before trial treatment is administered and again 30 minutes after the trial treatment is administered.

Standard coagulation parameters (platelets, fibrinogen, PT and aPTT time and D-dimer) and ROTEM® parameters measured after in vitro activation with tissue factor (EXTEM) and inhibition with aprotinin (APTEM) will be determined (maximum lysis, maximum strength [Maximal Clot Firmness (MCF)], time from start to when the waveform reaches 2mm above baseline [Clotting Time (CT)], time from 2mm above baseline to 20mm above baseline [Clot Formation Time (CFT)], time to lysis [CLT (10% difference from MCF)], time to Maximum strength [MCF-t], Clot elasticity [MCE]).

The hypothesis is that the administration of tranexamic acid will reduce markers of fibrinolytic activity in women with a clinical diagnosis of postpartum haemorrhage.

Added 08/01/2015:
WOMAN-ETAPLAT is a nested study of 128 participants in the WOMAN trial which aims to assess the effect of tranexamic acid on platelet function and thrombin generation in a sample of participants in the WOMAN trial. The primary outcome will be the effect of TXA on thrombin generation. Secondary outcomes will include effect of TXA on platelet function, fibrinogen, D-Dimer and coagulation factor V, VIII and vWF levels. Levels of all parameters will be assessed on venous blood samples. Samples will be collected at baseline and at between 30–60 minutes after the first dose of study treatment is given.

Ethics approval

LSHTM Ethics Committee (ref: 5536). All other centres will seek ethics approval before recruiting participants.

Study design

Large pragmatic randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Postpartum haemorrhage

Intervention

Women eligible for inclusion should be randomised, and the trial treatment started, as soon as possible. Randomisation to either active or placebo is done by telephoning a 24-hour freecall service. If telephone randomisation is not feasible a local pack system will be used where the next consecutively numbered treatment pack is taken from a box of eight packs. A loading dose of the trial treatment of tranexamic acid 1 g or placebo will be administered as soon possible, followed by a maintenance dose of tranexamic acid 1 g or placebo over eight hours. Outcome is collected at death, discharge or 6 weeks after randomisation, whichever occurs first.

Intervention type

Drug

Phase

Phase III

Drug names

Tranexamic acid

Primary outcome measures

1. Death (cause of death will be described)
2. Peripartum hysterectomy

The outcome is collected at death, discharge or 6 weeks after randomisation, whichever occurs first.

Added 08/01/2015:

WOMAN-ETAC (sub-study) primary outcome:
The primary outcome is to evaluate the effect of tranexamic acid on fibrinolysis 30 minutes after the first dose is given. Fibrinolysis will be measured with D-dimer, fibrinogen level and using ROTEM parameters previously reported to be associated with fibrinolysis (i.e., MCF, CA10, CA15, CLI30, and CLI60). Levels of all parameters will be assessed on venous blood samples.

WOMAN-ETAPlaT (sub-study) primary outcome:
The primary outcome is the effect of tranexamic acid on thrombin generation at 30-60 minutes after the first dose is given. Thrombin Generation Assay [Lag Time (LT, min), peak height or time to peak (nMol) and area under the curve or endogenous thrombin potential (ETP, measured in nmol/L per min)] Levels of all parameters will be assessed on venous blood samples.

Secondary outcome measures

1. Surgical interventions used to treat obstetric haemorrhage:
1.1. Hysterectomy
1.2. Any brace suture
1.3. Arterial ligation
1.4. Artery selective embolisation
2. Mortality (outcome added 08/01/2015)
3. Transfusion requirements (blood/components)
4. Thromboembolic events:
4.1. Deep venous thrombosis
4.2. Pulmonary thromboembolism
4.3. Stroke
4.4. Myocardial infarction
5. Length of stay in hospital
6. If an Intensive Care Unit is available, time spent in the ICU
7. Suspected Unexpected Serious Adverse Reactions (SUSAR)
8. Status of baby up to 6 weeks of delivery

The outcome is collected at death, discharge or 6 weeks after randomisation, whichever occurs first.

Added 08/01/2015:

WOMAN-ETAC (sub-study) secondary outcome:
As a secondary outcome we will evaluate the relationship between coagulation parameters and mortality.

WOMAN-ETAPlaT (Sub-study) secondary outcome:
Secondary outcomes will include effect of tranexamic acid on platelet function, fibrinogen, D-Dimer and coagulation factor V, VIII and vWF levels.

Overall trial start date

01/03/2009

Overall trial end date

30/05/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Immediately after delivery, all usual care should be given for the prevention of PPH. If bleeding continues and a clinician diagnosis of PPH is made, all usual treatments should be given and at the same time assessment for inclusion in the WOMAN Trial should be done. As most women die within 2 - 4 hours of delivery, it is important to consider inclusion as early as possible. Clinician diagnosis of PPH may be based on any of the following:
1. Blood loss after vaginal delivery greater than 500 ml, or
2. Greater than 1000 ml after caesarian section, or
3. Blood loss enough to compromise the haemodynamic status of the woman

Other inclusion criteria:
4. All women who are clinician-diagnosed with postpartum haemorrhage following vaginal delivery or caesarean section
5. Consent has been obtained in line with local procedures

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

20,000

Participant exclusion criteria

1. The responsible clinician is uncertain as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage
2. The responsible doctor considers there to be a clear indication for antifibrinolytic therapy
3. Women for whom there is considered to be a clear contraindication to antifibrinolytic therapy

When the responsible clinician is substantially uncertain as to whether or not to use an antifibrinolytic, all these women are eligible for randomisation and should be considered for the trial. There are no other pre-specified exclusion criteria.

Recruitment start date

01/03/2009

Recruitment end date

30/05/2016

Locations

Countries of recruitment

Albania, Bangladesh, Burkina Faso, Cameroon, Colombia, Egypt, Ethiopia, Ghana, Jamaica, Kenya, Nepal, Nigeria, Pakistan, Sudan, Tanzania, Uganda, United Kingdom, Zambia

Trial participating centre

London School of Hygiene and Tropical Medicine
London
WC1E 7HT
United Kingdom

Sponsor information

Organisation

London School of Hygiene and Tropical Medicine (LSHTM) (UK)

Sponsor details

Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)20 7299 4684
thewomantrial@lshtm.ac.uk

Sponsor type

University/education

Website

http://www.lshtm.ac.uk/

Funders

Funder type

University/education

Funder name

London School of Hygiene and Tropical Medicine

Alternative name(s)

London School of Hygiene & Tropical Medicine, LSHTM

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

United Kingdom

Funder name

Health Innovation Challenge Fund (Department of Health and Wellcome Trust) - award number HICF-0510-007

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United States of America

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20398351
2016 statistical analysis plan in: http://www.ncbi.nlm.nih.gov/pubmed/27188698

Publication citations

  1. Results

    Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E, Roberts I, The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial., Trials, 2010, 11, 40, doi: 10.1186/1745-6215-11-40.

  2. Statistical analysis plan

    Shakur H, Roberts I, Edwards P, Elbourne D, Alfirevic Z, Ronsmans C, 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, Trials, 2016 , 17, 1, 249, doi: 10.1186/s13063-016-1332-2.

Additional files

Editorial Notes

19/05/2016: Publication reference added. 08/01/2015: the following changes were made to the trial record: 1. The overall trial end date was changed from 31/12/2014 to 30/05/2016. 2. The target number of participants was changed from 15,000 to 20,000. 3. The following countries of recruitment were added: Bangladesh, Burkina Faso, Colombia, Egypt, Ethiopia, Ghana, Jamaica, Kenya, Nepal, Pakistan, Sudan, Tanzania, Uganda, United Kingdom, Zambia 4. The following funders were added: Health Innovation Challenge Fund (Department of Health and Wellcome Trust) - Award number HICF-0510-007; Bill & Melinda Gates Foundation 08/07/2010: the following countries of recruitment were added to this record: Albania, Cameroon.