World Maternal Antifibrinolytic Trial (WOMAN)
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.
Drug: Tranexamic acid
Drug: Placebo [Saline]
|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|
- 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 ]
- 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 ]
|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)|
|Active Comparator: Tranexamic acid||
Drug: Tranexamic acid
1-2 grams by intravenous injection
|Placebo Comparator: placebo||
Drug: Placebo [Saline]
Matched to active comparator
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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.
|Contact: Haleema Shakur, MSc, RN||++44 (0)firstname.lastname@example.org|
|University College Hospital||Recruiting|
|Principal Investigator: Oladapo Olayemi, MD|
|Study Director:||Ian G Roberts, MD||London School of Hygiene and Tropical Medicine|