Pharmacy and Poisons Board
Protocol No: ECCT/10/06/01 Date of Protocol: 11-05-2009
Study Title:

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

The WOMAN Trial aims to determine the effect of the early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed.

 
Laymans Summary:

The problem

Each year, worldwide, about 530,000 women die from causes related to pregnancy and childbirth and 99% of these women are from low and middle income countries.  Reducing maternal mortality by three quarters is a United Nations Millennium Development Goal (MDG), but at current rates of progress this is unlikely to be achieved.  Maternal deaths fell by less than 1% per year between 1990 and 2005, well below the 5.5% annual reduction needed to reach the MDG target by 2015.

Excessive bleeding soon after delivery is a major cause of maternal death.  About 14 million mothers have a postpartum haemorrhage each year and about 1% of these women will die.  Many more will have a hysterectomy leading to permanent sterility.  Other consequences of excessive bleeding include the need for a blood transfusion, which is not always available or safe, and severe anaemia which can seriously reduce a mother’s ability to look after her children or to work.  A simple and cost effective drug treatment to reduce blood loss after delivery could therefore have important consequences for global maternal health.

The Aim

The WOMAN trial (World Maternal Antifibrinolytic Trial) aims to determine the effect of the administration of the antifibrinolytic drug tranexamic acid on death and hysterectomy, and on other clinically relevant outcomes in women with diagnosed postpartum haemorrhage.

The intervention

Systemic antifibrinolytic drugs, including tranexamic acid, are widely used in surgery to prevent clot breakdown (fibrinolysis) and thus reduce surgical blood loss.  At present, the use of antifibrinolytic drugs in obstetrics and gynaecology is limited to the treatment of menorrhagia.  Currently there is insufficient reliable evidence to assess the effectiveness of tranexamic acid in obstetric bleeding.  This trial would provide a reliable basis for recommending whether or not tranexamic acid should be administered to women with severe postpartum haemorrhage.

The trial

The WOMAN trial is a large, international, randomised, placebo controlled trial, to quantify the safety and effect on mortality and morbidity of the administration of tranexamic acid in women with postpartum haemorrhage. Women who have clinician diagnosed postpartum haemorrhage after vaginal or caesarean section delivery will be eligible for the trial, except those for whom antifibrinolytic agents are thought to be clearly indicated or clearly contra-indicated.  Treatment will be allocated randomly and numbered drug /placebo packs will be available in participating obstetric departments. The primary outcome will be proportion of women who die or undergo hysterectomy. Outcomes will be assessed at death, discharge or 42 days after randomisation, whichever occurs first.

postpartum Haemorrhage accounts for around 25% of maternal deaths.  If a simple and widely practicable treatment, such as Tranexamic acid, could reduce blood loss following delivery, it could contribute importantly to the goal of reducing maternal mortality.  Tranexamic acid might also reduce the need for hysterectomy, decrease the risk of severe anaemia and avoid the need for blood transfusion.

 
Abstract of Study:

The problem

Each year, worldwide, about 530,000 women die from causes related to pregnancy and childbirth and 99% of these women are from low and middle income countries.  Reducing maternal mortality by three quarters is a United Nations Millennium Development Goal (MDG), but at current rates of progress this is unlikely to be achieved.  Maternal deaths fell by less than 1% per year between 1990 and 2005, well below the 5.5% annual reduction needed to reach the MDG target by 2015.

Excessive bleeding soon after delivery is a major cause of maternal death.  About 14 million mothers have a postpartum haemorrhage each year and about 1% of these women will die.  Many more will have a hysterectomy leading to permanent sterility.  Other consequences of excessive bleeding include the need for a blood transfusion, which is not always available or safe, and severe anaemia which can seriously reduce a mother’s ability to look after her children or to work.  A simple and cost effective drug treatment to reduce blood loss after delivery could therefore have important consequences for global maternal health.

The Aim

The WOMAN trial (World Maternal Antifibrinolytic Trial) aims to determine the effect of the administration of the antifibrinolytic drug tranexamic acid on death and hysterectomy, and on other clinically relevant outcomes in women with diagnosed postpartum haemorrhage.

The intervention

Systemic antifibrinolytic drugs, including tranexamic acid, are widely used in surgery to prevent clot breakdown (fibrinolysis) and thus reduce surgical blood loss.  At present, the use of antifibrinolytic drugs in obstetrics and gynaecology is limited to the treatment of menorrhagia.  Currently there is insufficient reliable evidence to assess the effectiveness of tranexamic acid in obstetric bleeding.  This trial would provide a reliable basis for recommending whether or not tranexamic acid should be administered to women with severe postpartum haemorrhage.

The trial

The WOMAN trial is a large, international, randomised, placebo controlled trial, to quantify the safety and effect on mortality and morbidity of the administration of tranexamic acid in women with postpartum haemorrhage. Women who have clinician diagnosed postpartum haemorrhage after vaginal or caesarean section delivery will be eligible for the trial, except those for whom antifibrinolytic agents are thought to be clearly indicated or clearly contra-indicated.  Treatment will be allocated randomly and numbered drug /placebo packs will be available in participating obstetric departments. The primary outcome will be proportion of women who die or undergo hysterectomy. Outcomes will be assessed at death, discharge or 42 days after randomisation, whichever occurs first.

Postpartum Haemorrhage accounts for around 25% of maternal deaths.  If a simple and widely practicable treatment, such as Tranexamic acid, could reduce blood loss following delivery, it could contribute importantly to the goal of reducing maternal mortality.  Tranexamic acid might also reduce the need for hysterectomy, decrease the risk of severe anaemia and avoid the need for blood transfusion.