World Maternal Antifibrinolytic Trial_2

NCT03475342 | Completed Phase 3 DMC

• 2 other identifiers: WOMAN_203475342
• Study Type: interventional
• Target: 15,068
• Locations: 4 countries
• Sites: 41

Brief Summary

Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, almost all of which occur in low and middle income countries. When given within three hours of birth, tranexamic acid reduces deaths due to bleeding in women with PPH by almost one third. However, for many women, treatment of PPH is too late to prevent death and severe morbidities. Over one-third of pregnant women in the world are anaemic and many are severely anaemic. We now want to do the WOMAN-2 trial to see if giving tranexamic acid can prevent PPH and other severe outcomes in women with moderate and severe anaemia.

Conditions

Intrapartum - Moderate and Severe Anaemia

Keywords

prevention, postpartum haemorrhage; moderate anaemia; severe anaemia; antifibrinolytic; tranexamic acid; pregnancy; pain; episiotomy

Outcome Measures

Primary Outcomes (1)

• Postpartum Haemorrhage (cause will be described)

  Clinical assessment: This may be an estimated blood loss of more than 500 mL or any blood loss sufficient to compromise haemodynamic stability within 24 hours of delivery. Haemodynamic instability is based on clinical judgement and assessed using clinical signs (low systolic blood pressure, tachycardia, reduced urine output).

  24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier

Secondary Outcomes (19)

• Postpartum blood loss

  24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier

• Haemoglobin

  24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier

• Haemodynamic instability

  24 hours after administration of trial treatment or discharge from hospital, whichever is earlier

• Shock index

  24 hours after administration of trial treatment or discharge from hospital, whichever is earlier

• Quality of Life (maternal)

  Day 42 or discharge from hospital, whichever is earlier

Study Arms (2)

Tranexamic acid

ACTIVE COMPARATOR

One intravenous injection of tranexamic acid. Total dose 1 gram (10mL)

Drug: Tranexamic Acid

Placebo

PLACEBO COMPARATOR

One Injection of the placebo which is 10 mL Sodium Chloride (0.9%)

Other: Placebo

Interventions

Tranexamic Acid DRUG

Ampoules and packaging for both arms will be identical in appearance.

Tranexamic acid

Placebo OTHER

Ampoules and packaging for both arms will be identical in appearance.

Also known as: (Sodium Chloride 0.9%)

Placebo

Eligibility Criteria

• Gender Eligibility Details: Women who have given birth
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with moderate or severe anaemia (haemoglobin level \<100 g/L or packed cell volume \<30%) after giving birth vaginally where the responsible clinician is substantially uncertain whether to use TXA

You may not qualify if:

• Women who are not legally adult (\<18 years) and not accompanied by a guardian
• Women with a known allergy to tranexamic acid or its excipients
• Women who experience postpartum haemorrhage before the umbilical cord is cut or clamped.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Wellcome Trust: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (41)

Mother & Child Hospital

Akure, Nigeria

Location

University of Medical Sciences Teaching Hospital

Akure, Nigeria

Location

Adeoyo Maternity Hospital

Ibadan, Nigeria

Location

Ilorin General Hospital

Ilorin, Nigeria

Location

Muhammad Abdullahi Wase Specialist Hospital

Kano, Nigeria

Location

Ladoke Akintola University of Technology Teaching Hospital

Ogbomoso, Nigeria

Location

State Hospital

Oyo, Nigeria

Location

Ayub Teaching Hospital (Unit A)

Abbottabad, Pakistan

Location

Ayub Teaching Hospital (Unit C)

Abbottabad, Pakistan

Location

Ayub Teaching Hospital Unit B

Abbottabad, Pakistan

Location

Bahawalpur Victoria Hospital

Bahawalpur, Pakistan

Location

Aziz Bhatti Teaching Hospital

Gujrat, Pakistan

Location

MCH PIMS

Islamabad, Pakistan

Location

Military Hospital

Islamabad, Pakistan

Location

Civil Hospital

Karachi, Pakistan

Location

Jinnah Postgraduate Medical Centre

Karachi, Pakistan

Location

Koohi Goth Hospital

Karachi, Pakistan

Location

Jinnah Hospital

Lahore, Pakistan

Location

Services Hospital

Lahore, Pakistan

Location

Sir Ganga Ram Hospital Unit 1

Lahore, Pakistan

Location

Sir Ganga Ram Hospital Unit 2

Lahore, Pakistan

Location

Sir Ganga Ram Hospital Unit 3

Lahore, Pakistan

Location

Sir Ganga Ram Hospital Unit 4

Lahore, Pakistan

Location

Chandka SMBBMU Sheikh Zaid Woman Hospital Unit 1

Larkana, Pakistan

Location

Chandka SMBBMU Sheikh Zaid Woman Hospital Units 2 & 3

Lārkāna, Pakistan

Location

Nishtar Hospital Unit 1

Multan, Pakistan

Location

Nishtar Hospital Unit 2

Multan Khurd, Pakistan

Location

Nishtar Hospital Unit 3

Multan Khurd, Pakistan

Location

Bolan Medical Centre

Quetta, Pakistan

Location

Benazir Bhutto Shaheed Hospital

Rawalpindi, Pakistan

Location

Federal Government Polyclinic

Rawalpindi, Pakistan

Location

Holy Family Hospital

Rawalpindi, Pakistan

Location

Mount Meru Regional Referral Hospital

Arusha, Tanzania

Location

Amana Regional Referral Hospital,

Dar es Salaam, Tanzania

Location

Muhimbili National Hospital

Dar es Salaam, Tanzania

Location

Temeke Regional Referral Hospital

Dar es Salaam, Tanzania

Location

Dodoma Regional Referral Hospital

Dodoma, Tanzania

Location

Tumbi Regional Referral Hospital, Kibaha

Kibaha, Tanzania

Location

Mwananyamala Regional Referral Hospital

Kinondoni, Tanzania

Location

Mbeya Zonal Referral Hospital

Mbeya, Tanzania

Location

Women and Newborn Hospital

Lusaka, Zambia

Location

Related Publications (5)

• WOMAN-2 Trial Collaborators. The effect of tranexamic acid on postpartum bleeding in women with moderate and severe anaemia (WOMAN-2): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2024 Oct 26;404(10463):1645-1656. doi: 10.1016/S0140-6736(24)01749-5.

  PMID: 39461792 DERIVED

• Larson NJ, Mergoum AM, Dries DJ, Cook A, Blondeau B, Rogers FB. THE ROLE OF TRANEXAMIC ACID IN POSTPARTUM HEMORRHAGE: A NARRATIVE REVIEW. Shock. 2024 Nov 1;62(5):620-627. doi: 10.1097/SHK.0000000000002455. Epub 2024 Aug 20.

  PMID: 39162220 DERIVED

• Collier T, Shakur-Still H, Roberts I, Balogun E, Olayemi O, Bello FA, Chaudhri R, Muganyizi P; WOMAN-2 Trial Collaborators. Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: Statistical analysis plan for the WOMAN-2 trial: an international, randomised, placebo-controlled trial. Gates Open Res. 2023 Aug 3;7:69. doi: 10.12688/gatesopenres.14529.2. eCollection 2023.

  PMID: 37664793 DERIVED

• Brenner A, Roberts I, Balogun E, Bello FA, Chaudhri R, Fleming C, Javaid K, Kayani A, Lubeya MK, Mansukhani R, Olayemi O, Prowse D, Vwalika B, Shakur-Still H. Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials. Trials. 2022 Mar 18;23(1):220. doi: 10.1186/s13063-022-06140-z.

  PMID: 35303924 DERIVED

• Ker K, Roberts I, Chaudhri R, Fawole B, Beaumont D, Balogun E, Prowse D, Pepple T, Javaid K, Kayani A, Arulkumaran S, Bates I, Shakur-Still H; WOMAN-2 trial collaborators. Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: study protocol for an international, randomised, double-blind, placebo-controlled trial. Trials. 2018 Dec 29;19(1):712. doi: 10.1186/s13063-018-3081-x.

  PMID: 30594227 DERIVED

MeSH Terms

Conditions

Anemia; Postpartum Hemorrhage; Pain

Interventions

Tranexamic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Ian Roberts

  Clinical Trials Unit, London School of Hygiene and Tropical Medicine

  STUDY CHAIR

• Haleema Shakur-Still

  Clinical Trials Unit, London School of Hygiene and Tropical Medicine

  STUDY CHAIR

• Rizwana Chaudhri

  National Coordinating Investigator, Shifa Tameer-e-Millat University, Pakistan

  PRINCIPAL INVESTIGATOR

• Folasade A Bello

  National Coordinating Investigator, College of Medicine, University of Ibadan, Nigeria

  PRINCIPAL INVESTIGATOR

• Bellington Vwalika

  National Coordinating Investigator, University of Zambia School of Medicine, Zambia

  PRINCIPAL INVESTIGATOR

• Projestine Muganyizi

  National Coordinating Investigator, Muhimbili University of Health and Allied Sciences, Tanzania

  PRINCIPAL INVESTIGATOR

• Oladapo Olayemi

  National Coordinating Investigator, College of Medicine, University of Ibadan, Nigeria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking was done by an independent clinical trials supply company. It will involve the removal of the original manufacturer's label and replacement with the clinical trial label bearing the randomisation number, which will be used as the pack identification. Apart from the randomisation number, all pack label texts will be identical for tranexamic acid and placebo.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomised, double blind, placebo controlled trial among 15,000 women with moderate or severe anaemia having given birth vaginally.

Study Record Dates

• First Submitted: February 23, 2018
• First Posted: March 23, 2018
• Study Start: August 24, 2019
• Primary Completion: September 20, 2023
• Study Completion: October 29, 2023
• Last Updated: January 10, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be shared publicly when all planned analyses are completed by the Woman-2 Trial Collaborators.
• Access Criteria: Totally anonymised data (without random allocation, patient, country and site identifiers) will be freely available. Where random allocation codes, country/site identifiers are requested, appropriate pre-specified analysis plan will need to be submitted to the Trial Management Group for review and if necessary, appropriate Ethics Committee approval will be required.

Locations

PA (25); NG (7); ZA (1); TA (8)