Tranexamic Acid to Prevent Heavy Bleeding After Childbirth in Women At Higher Risk (I'M-WOMAN)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Tranexamic acid; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amy Brenner; Phone Number: +44 (0)20 7958 8283; Email: imwoman@lshtm.ac.uk
• Study Contact Backup: Name: Ian Roberts; Phone Number: +44 (0)20 7958 8128

Study Locations

• Tanzania
  • Mbeya, Tanzania
    • Recruiting
    • Mbeya Regional Referral Hospital
    • Contact: Soter Vitalis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: UNITAID
• Investigators: Study Director: Amy Brenner, London School oh Hygiene and Tropical Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: September 27, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: bleeding; pregnancy; tranexamic acid; postpartum haemorrhage; intramuscular; antifibrinolytic
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Puerperal Disorders; Uterine Hemorrhage; Postpartum Hemorrhage; Hemorrhage; Molecular Mechanisms of Pharmacological Action; Antifibrinolytic Agents; Fibrin Modulating Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: IMWOMAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators are committed to sharing data for ethical research with justified scientific objectives. Until all planned analyses are completed by the LSHTM CTU Global Health Trials Group, data will be shared through a controlled access approach whereby researchers can make formal applications for data sharing. Afterwards, the anonymised dataset will be shared via the LSHTM CTU Global Health Trials Group data sharing platform at freebird.lshtm.ac.uk. All trial materials including training materials, CRFs and Protocol will be made available on the trial website and team YouTube channel.
• IPD Sharing Time Frame: Once all planned analyses are completed by the LSHTM CTU Global Health Trials Group following trial completion. Data will be shared indefinitely.
• IPD Sharing Access Criteria: As above
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No