Tranexamic Acid to Prevent Heavy Bleeding After Childbirth in Women at Higher Risk

Study Overview
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Brief Summary
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Heavy bleeding after childbirth, known as a postpartum haemorrhage (PPH), causes about 70,000 maternal deaths every year. Tranexamic acid (TXA) is a lifesaving treatment for women with PPH. The I'M WOMAN trial is a research study to see whether giving TXA just before childbirth will stop women developing PPH. The trial will assess the effects of intramuscular (IM) and intravenous (IV) tranexamic acid on PPH, side effects and other important maternal health outcomes.

Detailed Description
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Postpartum haemorrhage (PPH) causes about 70,000 maternal deaths every year. Tranexamic acid (TXA) is a lifesaving treatment for women with PPH. The WOMAN trial recruited over 20,000 women with PPH and found that intravenous (IV) TXA given soon after PPH onset, reduces bleeding deaths by about a third. Early TXA also reduces blood loss in surgery and death due to bleeding after traumatic injury. The World Health Organization recommends that all women with PPH should receive TXA as a first line treatment. TXA is more effective when given soon after the bleeding starts. Every fifteen minute delay reduces the survival benefit by about 10%. This suggests that giving TXA around the time of childbirth might prevent PPH. Although several clinical trials have examined the effectiveness of TXA for the prevention of PPH, the results are inconclusive. Trials of tranexamic acid for PPH prevention give the trial treatment after cord clamping, which may be too late to prevent bad bleeding in some women, as bleeding tends to happen soon after childbirth. Because PPH only affects a small proportion of births, the healthcare community need good evidence on the balance of benefits and harms in this population before using TXA to prevent PPH. The I'M WOMAN trial will evaluate the effects of TXA for PPH prevention in women with one or more risk factors for PPH having a vaginal or caesarean birth. The trial will also evaluate the effect of the route of TXA administration. TXA is usually given by slow IV injection. However, recent research shows that TXA is well tolerated and rapidly absorbed after IM injection, achieving therapeutic blood levels within minutes of injection. There may be fewer side effects with IM TXA because peak blood concentrations are lower than with the IV route, as well as practical advantages.

Official Title
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Tranexamic Acid by the Intramuscular or Intravenous Route for the Prevention of Postpartum Haemorrhage in Women at Increased Risk: a Randomised, Double-blind, Placebo-controlled Trial

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic acid
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 years or older who are admitted to hospital to give birth vaginally or by caesarean section, who have one or more known risk factors for PPH Exclusion Criteria: Women who have a clear indication or contraindication for TXA

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intramuscular TXA<br>1g TXA as 2 x 5 ml IM injections (100mg/ml) and slow IV injection of placebo (1 x 10 ml of 0.9% sodium chloride) | Drug: Tranexamic acid<br>* Ampoules and packaging for all arms will be identical in appearance.<br>* Other names: Cyklokapron;Other: Placebo<br>* Ampoules and packaging for all arms will be identical in appearance.<br>* Other names: (Sodium Chloride 0.9%);|
| Active Comparator: Intravenous TXA<br>1g TXA by slow IV injection and 2 x 5 ml IM injections of placebo | Drug: Tranexamic acid<br>* Ampoules and packaging for all arms will be identical in appearance.<br>* Other names: Cyklokapron;Other: Placebo<br>* Ampoules and packaging for all arms will be identical in appearance.<br>* Other names: (Sodium Chloride 0.9%);|
| Placebo Comparator: Placebo<br>Placebo by 1 x slow 10ml IV injection and 2 x 5 ml IM injections | Other: Placebo<br>* Ampoules and packaging for all arms will be identical in appearance.<br>* Other names: (Sodium Chloride 0.9%);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of Postpartum haemorrhage | Clinical assessment: This may be an estimated blood loss of more than 500 mL in vaginal births or more than 1000 ml in caesarean births, or any blood loss sufficient to compromise haemodynamic stability. Haemodynamic instability is based on clinical judgement and assessed using clinical signs (low systolic blood pressure, tachycardia, reduced urine output) | within 24 hours of childbirth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tranexamic acid, postpartum haemorrhage, bleeding, pregnancy, antifibrinolytic, intramuscular