Plain English Summary
Not provided at time of registration
Trial website
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 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 measure
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 (if study stopped)
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
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
Universities (academic only)
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, Gates Foundation, 比尔及梅琳达·盖茨基金会, बिल एंड मिलिंडा गेट्स फाउंडेशन, BMGF, B&MGF
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both publically funded and privately funded)
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
Basic results (scientific)
Publication list
2010 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/20398351
2016 statistical analysis plan in: http://www.ncbi.nlm.nih.gov/pubmed/27188698
2016 WOMAN-ETAC sub-study protocol and statistical analysis plan in: https://www.ncbi.nlm.nih.gov/pubmed/28317031
2016 WOMAN-ETAPlaT sub-study statistical analysis plan in: https://www.ncbi.nlm.nih.gov/pubmed/28413832
2017 results in: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30638-4/fulltext
2018 exploratory subgroup analysis results in: http://www.ncbi.nlm.nih.gov/pubmed/29879947
Publication citations
-
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.
-
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.