WOrld Maternal ANtifibrinolytic Trial
| ISRCTN | ISRCTN76912190 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76912190 |
| ClinicalTrials.gov number | NCT00872469 |
| Secondary identifying numbers | N/A |
- Submission date
- 08/12/2008
- Registration date
- 10/12/2008
- Last edited
- 11/06/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Ms Haleema Shakur
Scientific
Scientific
Department of Epidemiology and Population Health
London School of Hygiene and Tropical Medicine
Keppel Street
London
WC1E 7HT
United Kingdom
| Phone | +44 (0)20 7299 4684 |
|---|---|
| thewomantrial@lshtm.ac.uk |
Study information
| Study design | Large pragmatic randomised double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind, placebo controlled trial |
| Study acronym | WOMAN |
| Study objectives | 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(s) | LSHTM Ethics Committee, ref: 5536 All other centres will seek ethics approval before recruiting participants |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/03/2009 |
| Completion date | 30/05/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 20,000 |
| Key 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 |
| Key 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. |
| Date of first enrolment | 01/03/2009 |
| Date of final enrolment | 30/05/2016 |
Locations
Countries of recruitment
- Albania
- Bangladesh
- Burkina Faso
- Cameroon
- Colombia
- Egypt
- England
- Ethiopia
- Ghana
- Jamaica
- Kenya
- Nepal
- Nigeria
- Pakistan
- Sudan
- Tanzania
- Uganda
- United Kingdom
- Zambia
Study participating centre
London School of Hygiene and Tropical Medicine
London
WC1E 7HT
United Kingdom
WC1E 7HT
United Kingdom
Sponsor information
London School of Hygiene and Tropical Medicine (LSHTM) (UK)
University/education
University/education
Keppel Street
London
WC1E 7HT
England
United Kingdom
| Phone | +44 (0)20 7299 4684 |
|---|---|
| thewomantrial@lshtm.ac.uk | |
| Website | http://www.lshtm.ac.uk/ |
"ROR" |
https://ror.org/00a0jsq62 |
Funders
Funder type
University/education
London School of Hygiene and Tropical Medicine
Private sector organisation / Universities (academic only)
Private sector organisation / Universities (academic only)
- Alternative name(s)
- London School of Hygiene & Tropical Medicine, LSHTM
- Location
- United Kingdom
Health Innovation Challenge Fund (Department of Health and Wellcome Trust) - award number HICF-0510-007
No information available
Bill and Melinda Gates Foundation
Government organisation / Trusts, charities, foundations (both public and private)
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 16/04/2010 | Yes | No | |
| Statistical Analysis Plan | statistical analysis plan | 17/05/2016 | No | No | |
| Statistical Analysis Plan | WOMAN-ETAPlaT sub-study statistical analysis plan | 15/12/2016 | No | No | |
| Protocol article | WOMAN-ETAC sub-study protocol and statistical analysis plan | 16/12/2016 | Yes | No | |
| Results article | results | 01/05/2017 | Yes | No | |
| Results article | exploratory subgroup analysis results | 07/06/2018 | Yes | No |
Editorial Notes
11/06/2018: Publication reference added.
27/04/2017: Publication references added.
21/03/2017: Publication reference added.
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.
