World Maternal Antifibrinolytic Trial (WOMAN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by London School of Hygiene and Tropical Medicine
Sponsor:
Collaborator:
Indian Council of Medical Research
Information provided by:
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT00872469
First received: March 30, 2009
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

This trial is a large pragmatic randomised double-blind, placebo controlled trial to quantify the effects of the early administration of tranexamic acid on death, hysterectomy and other relevant outcomes. 15,000 adult women, after delivery who have clinically diagnosed postpartum haemorrhage, are eligible if the responsible doctor is for any reason substantially uncertain whether or not to use an antifibrinolytic agent.


Condition Intervention Phase
Postpartum Haemorrhage
Drug: Tranexamic acid
Drug: Placebo [Saline]
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tranexamic Acid for the Treatment of Postpartum Haemorrhage: An International Randomised, Double Blind, Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • The primary outcome is the proportion of women who die or undergo hysterectomy. The primary cause of death will be described. [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Surgical Interventions including hysterectomy; brace suture; selective arterial embolisation; laparotomy for other reasons; manual removal of placenta; intrauterine tamponade; artery ligation, to achieve haemostasis. [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: Yes ]
  • Need for blood transfusion - blood or blood component units transfused. [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: Yes ]
  • Health Status measured using the EQ-5D. [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: No ]
  • Thromboembolic events (myocardial infarction, strokes, pulmonary embolism, DVT). [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: Yes ]
  • Other relevant medical events [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: Yes ]
  • Length of stay at hospital/time spent at an intensive care unit [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: No ]
  • Need for mechanical ventilation. [ Time Frame: up to 42 days after randomisation ] [ Designated as safety issue: No ]
  • Status of baby/ies [ Time Frame: up to 42 weeks after randomisation of mother ] [ Designated as safety issue: Yes ]
  • Cost-effectiveness analysis [ Designated as safety issue: No ]

Estimated Enrollment: 15000
Study Start Date: May 2009
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tranexamic acid Drug: Tranexamic acid
1-2 grams by intravenous injection
Placebo Comparator: placebo Drug: Placebo [Saline]
Matched to active comparator

  Hide Detailed Description

Detailed Description:

BACKGROUND: Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Almost all (99%) of the deaths are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality accounting for between one quarter and one third of deaths, most of which occur in the postpartum period. About 14 million mothers develop postpartum haemorrhage (PPH) each year and about 1-2% of them will die, with an average interval from onset to death of about 2 to 4 hours. Obstetric haemorrhage is also an important cause of maternal mortality in high income countries where it accounts for about 13% of maternal deaths.

Anti-fibrinolytic agents are widely used in surgery to reduce blood loss and the need for blood transfusion. A systematic review of randomised controlled trials of anti-fibrinolytic agents in elective surgery showed that tranexamic acid (TXA) reduced the risk of blood transfusion by a relative 39% (RR 0.61, 95% CI 0.54 to 0.69). In those requiring transfusion, TXA reduced the transfused blood volume by 1.1 units (95% CI 0.64 to 1.59). Anti-fibrinolytic agents also reduced the need for re-operation due to bleeding (RR=0.52: 95% CI 0.40 to 0.69). There was no evidence of an increased risk of thrombotic events.

TXA significantly reduces uterine blood loss in women with menorrhagia and is "recommended for consideration" as a treatment in intractable postpartum haemorrhage in the UK. However, at present there is little reliable evidence from randomised trials on the effectiveness of TXA in the treatment of PPH. A systematic review of randomised trials of TXA in PPH conducted by the applicants identified three trials of the prophylactic use of TXA, including a total of 460 participants. Although there was a significant reduction in average postpartum blood loss in women treated with TXA [weighted mean reduction 96 ml (95%CI 76ml to 109ml)] the quality of the trials was poor. None had adequate allocation concealment and even in aggregate the trials were too small to assess the effects of TXA on the clinically important end points of mortality, hysterectomy and thrombotic side effects. The most recently updated PPH treatment guidelines prepared by the World Health Organization (WHO) state that TXA may be used in the treatment of PPH if other measures fail, but points out that the quality of evidence on which this recommendation is based is low and recommends that further clinical trials of TXA in PPH are conducted.

AIM: The WOMAN Trial aims to determine the effect of the early administration of tranexamic acid (TXA) on death and hysterectomy in women with a clinical diagnosis of postpartum haemorrhage. The effect of TXA on the need for surgical interventions, blood transfusion, the risk of non-fatal vascular events (either haemorrhagic or occlusive), use of health services and breastfeeding will also be assessed.

OUTCOME: Outcomes will be collected at 42 days after randomisation, at discharge or at death (whichever occurs first).

TEST PRODUCT, DOSE AND MODE OF ADMINISTRATION: A first dose of Tranexamic acid (1 gram by intravenous injection) will be given as soon as possible after randomisation. If clinically indicated due to continued bleeding, a second dose of Tranexamic acid (1 gram by intravenous injection) will be given if within 4 hours of randomisation.

REFERENCE THERAPY, DOSE AND MODE OF ADMINISTRATION: A placebo (sodium chloride 0.9%) matched to the active drug will be administered in the same way as the active product. A placebo is justified in this trial because all women with PPH will receive all other treatments clinically indicated. Tranexamic acid/placebo will be given as an additional treatment.

SETTING: This trial will be co-ordinated from LSHTM and conducted in hospitals in low, middle and high income countries. It is likely that most patient recruitment will be in countries with high rates of mortality and morbidity from postpartum haemorrhage.

DURATION OF TREATMENT AND PARTICIPATION: The first dose will be given immediately after randomisation. If required, the second dose will be given up to 24 hours after randomisation. No further trial treatment will be given after 24 hours of randomisation. Participation will end at discharge, death or at 42 days post randomisation whichever occurs first.

CRITERIA FOR EVALUATION: All patients randomly assigned to one of the treatments will be analysed together, regardless of whether or not they completed or received that treatment on an intention to treat basis.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

All legally adult women with postpartum haemorrhage following vaginal or caesarean section delivery who have a clinical diagnosis of postpartum haemorrhage. The clinical diagnosis of PPH may be based on any of the following:

  • Blood loss after vaginal delivery > 500 mL OR
  • > 1,000 mL after caesarean section OR blood loss sufficient to compromise the haemodynamic status of the woman The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage.
  • Women for whom the responsible doctor considers there is a clear indication for antifibrinolytic therapy should not be randomised.
  • Women for whom there is considered to be a clear contraindication to antifibrinolytic therapy should not be randomised.

Where 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00872469

Contacts
Contact: Haleema Shakur, MSc, RN ++44 (0)20-7958-8113 thewomantrial@lshtm.ac.uk

Locations
Nigeria
University College Hospital Recruiting
Ibadan, Nigeria
Principal Investigator: Oladapo Olayemi, MD         
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Indian Council of Medical Research
Investigators
Study Director: Ian G Roberts, MD London School of Hygiene and Tropical Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Professor Ian Roberts, London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT00872469     History of Changes
Other Study ID Numbers: ISRCTN76912190
Study First Received: March 30, 2009
Last Updated: October 3, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
India: Indian Council of Medical Research
Nigeria: The National Agency for Food and Drug Administration and Control

Keywords provided by London School of Hygiene and Tropical Medicine:
Postpartum haemorrhage
randomised controlled trial
tranexamic acid
antifibrinolytic

Additional relevant MeSH terms:
Hemorrhage
Postpartum Hemorrhage
Pathologic Processes
Obstetric Labor Complications
Pregnancy Complications
Puerperal Disorders
Uterine Hemorrhage
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014