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World Maternal Antifibrinolytic Trial_2 (WOMAN-2)

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ClinicalTrials.gov Identifier: NCT03475342
Recruitment Status : Not yet recruiting
First Posted : March 23, 2018
Last Update Posted : March 14, 2019
Sponsor:
Collaborators:
Wellcome Trust
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

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.

Condition or disease Intervention/treatment Phase
Intrapartum - Moderate and Severe Anaemia Drug: Tranexamic Acid Other: Placebo Phase 3

Detailed Description:

Anaemia is a cause and consequence of PPH. A cohort study in Assam, India found that women with moderate or severe anaemia had a greatly increased risk of PPH. Women with moderate anaemia had a 50% increased risk, whereas those with severe anaemia had a ten-fold increased risk of PPH. Anaemic women may be more susceptible to uterine atony due to impaired oxygen transport to the uterus. Anaemic women experience worse outcomes after PPH. An international survey of 275,000 women found that severe maternal outcomes after PPH were nearly three times more common in anaemic than in non-anaemic women. Even moderate bleeding can be life threatening in anaemic women. Excessive bleeding after childbirth worsens maternal anaemia, resulting in a vicious circle of bleeding and adverse outcomes. Fatigue due to anaemia severely limits a mothers' wellbeing and her ability to care for her children. Despite efforts to prevent anaemia, many women labour with perilously low haemoglobin levels

Tranexamic acid (TXA) inhibits fibrinolysis by blocking the lysine binding sites on plasminogen. TXA reduces surgical bleeding and death due to bleeding in trauma patients. The WOMAN trial assessed the effects of TXA in 20,060 women with PPH. When given within three hours of birth, TXA reduced death due to bleeding by nearly one-third (RR=0.69, 95% CI 0.52 to 0.91, p=0.008). However, for many women, treatment is too late to prevent death from PPH. Most PPH deaths occur in the first hours after giving birth and women with anaemia are at greatly increased risk. Whilst there have been some trials of TXA for the prevention of PPH, most have serious flaws and none collected data on maternal health and wellbeing. There is currently no reliable evidence about the effectiveness and safety of TXA for preventing PPH.

The WOMAN-2 trial will determine reliably the effects of TXA in anaemic women who give birth vaginally.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomised, double blind, placebo controlled trial among 10,000 women with moderate or severe anaemia having given birth vaginally.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Prevention
Official Title: Tranexamic Acid for the Prevention of Postpartum Bleeding in Women With Anaemia: an International, Randomised, Double-blind, Placebo Controlled Trial.
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Tranexamic acid
One intravenous injection of tranexamic acid. Total dose 1 gram (10mL)
Drug: Tranexamic Acid
Ampoules and packaging for both arms will be identical in appearance.

Placebo Comparator: Placebo
One Injection of the placebo which is 10 mL Sodium Chloride (0.9%)
Other: Placebo
Ampoules and packaging for both arms will be identical in appearance.
Other Name: (Sodium Chloride 0.9%)




Primary Outcome Measures :
  1. Postpartum Haemorrhage (cause will be described) [ Time Frame: 24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier ]
    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).


Secondary Outcome Measures :
  1. Postpartum blood loss [ Time Frame: 24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier ]
    Clinical assessment

  2. Haemaglobin [ Time Frame: 24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier ]
    Haemacue (Point of care test)

  3. Haemodynamic instability [ Time Frame: 24 hours after administration of trial treatment or discharge from hospital, whichever is earlier ]
    Defined as per protocol

  4. Shock index [ Time Frame: 24 hours after administration of trial treatment or discharge from hospital, whichever is earlier ]
    Heart rate/systolic blood pressure

  5. Quality of Life (maternal) [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    Defined as per protocol

  6. Expected side effects of trial medication [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    nausea, vomiting, diarrhoea

  7. Exercise tolerance [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    6 minute walk test

  8. Interventions to control primary postpartum haemorrhage (medical and surgical) [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    Any of the following: uterotonics, removal of placenta/placenta fragments, intrauterine balloon tamponade, bimanual uterine compression, external aortic compression, non-pneumatic anti-shock garments, uterine artery embolisation, uterine compression suture, hysterectomy and laparotomy to control bleeding

  9. Receipt of blood product transfusion [ Time Frame: Day 42 or discharge of mother from hospital, whichever is earlier ]
    units and type

  10. Vascular occlusive events [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    Any of the following:pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, myocardial infarction

  11. Symptoms of anaemia [ Time Frame: Day 42 or discharge of mother from hospital, whichever is earlier ]
    measured using Quality of life Questionnaire and walk test

  12. Organ disfunction [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    Any of the following: Cardiovascular, Respiratory, Renal, Hepatic, Neurological, Coagulation/ haematologic dysfunction

  13. Sepsis [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    diagnosis is based on the presence of both infection and a systemic inflammatory response syndrome (SIRS). SIRS requires two or more of the following: a) temperature <36°C or >38°C (b) heart rate >90 beats/min (c) respiratory rate >20 breaths/min (d) white blood cell count <4x109/L (<4000/mm³) or >12x109/L (>12,000/mm³)

  14. In hospital death [ Time Frame: Day 42 ]
    Cause and time of death will be described

  15. Length of hospital stay. [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    Days

  16. Admission to and time spent in higher level facility [ Time Frame: Day 42 or discharge from hospital, whichever is earlier ]
    High Dependency and/or Intensive Care Units

  17. Status of baby/ies [ Time Frame: Day 42 or discharge of mother from hospital, whichever is earlier ]
    alive or dead

  18. Thromboembolic events in breastfed babies [ Time Frame: Day 42 or discharge of mother from hospital, whichever is earlier ]
    as defined in protocol

  19. Adverse events [ Time Frame: Day 42 ]
    Any untoward medical occurance (other than expected complications)



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women who have given birth
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03475342


Contacts
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Contact: Haleema Shakur-Still, MSc +44(0)20-7958-8113 woman2@lshtm.ac.uk
Contact: Ian Roberts, MD +44(0)20-7958-8128

Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Wellcome Trust
Bill and Melinda Gates Foundation
Investigators
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Study Chair: Ian Roberts, MD 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
Principal Investigator: Rizwana Chaudhri National Coordinating Investigator, Rawalpindi Medical University, Pakistan
Principal Investigator: Bukola Fawole National Coordinating Investigator, University College Hospital, Nigeria
Principal Investigator: Sam Ononge Maker ere University College of Health, Kampala, Uganda

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03475342     History of Changes
Other Study ID Numbers: WOMAN_2
03475342 ( Other Identifier: ISRCTN )
First Posted: March 23, 2018    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared publicly when all planned analyses are completed by the Woman-2 Trial Collaborators. This will be hosted on freebird.lshtm.ac.uk
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.

URL: http://freebird.lshtm.ac.uk

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by London School of Hygiene and Tropical Medicine:
prevention, postpartum haemorrhage
moderate anaemia
severe anaemia
antifibrinolytic
tranexamic acid
pregnancy

Additional relevant MeSH terms:
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Anemia
Hematologic Diseases
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants