WOMAN-2: World Maternal Antifibrinolytic Trial_2
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Postpartum Haemorrhage (cause will be described) [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
- Postpartum blood loss [24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier]
Clinical assessment
- Haemaglobin [24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier]
Haemacue (Point of care test)
- Haemodynamic instability [24 hours after administration of trial treatment or discharge from hospital, whichever is earlier]
Defined as per protocol
- Shock index [24 hours after administration of trial treatment or discharge from hospital, whichever is earlier]
Heart rate/systolic blood pressure
- Quality of Life (maternal) [Day 42 or discharge from hospital, whichever is earlier]
Defined as per protocol
- Expected side effects of trial medication [Day 42 or discharge from hospital, whichever is earlier]
nausea, vomiting, diarrhoea
- Exercise tolerance [Day 42 or discharge from hospital, whichever is earlier]
6 minute walk test
- Interventions to control primary postpartum haemorrhage (medical and surgical) [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
- Receipt of blood product transfusion [Day 42 or discharge of mother from hospital, whichever is earlier]
units and type
- Vascular occlusive events [Day 42 or discharge from hospital, whichever is earlier]
Any of the following:pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, myocardial infarction
- Symptoms of anaemia [Day 42 or discharge of mother from hospital, whichever is earlier]
measured using Quality of life Questionnaire and walk test
- Organ disfunction [Day 42 or discharge from hospital, whichever is earlier]
Any of the following: Cardiovascular, Respiratory, Renal, Hepatic, Neurological, Coagulation/ haematologic dysfunction
- Sepsis [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)
- In hospital death [Day 42]
Cause and time of death will be described
- Length of hospital stay. [Day 42 or discharge from hospital, whichever is earlier]
Days
- Admission to and time spent in higher level facility [Day 42 or discharge from hospital, whichever is earlier]
High Dependency and/or Intensive Care Units
- Status of baby/ies [Day 42 or discharge of mother from hospital, whichever is earlier]
alive or dead
- Thromboembolic events in breastfed babies [Day 42 or discharge of mother from hospital, whichever is earlier]
as defined in protocol
- Adverse events [Day 42]
Any untoward medical occurance (other than expected complications)
Eligibility Criteria
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
-
Women who experience postpartum haemorrhage before the umbilical cord is cut or clamped.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Abuja Teaching Hospital, Gwagalada | Abuja | Nigeria | ||
| 2 | Mother & Child Hospital | Akure | Nigeria | ||
| 3 | University of Medical Sciences Teaching Hospital | Akure | Nigeria | ||
| 4 | Adeoyo Maternity Hospital | Ibadan | Nigeria | ||
| 5 | Ilorin General Hospital | Ilorin | Nigeria | ||
| 6 | Muhammad Abdullahi Wase Specialist Hospital | Kano | Nigeria | ||
| 7 | Ladoke Akintola University of Technology Teaching Hospital | Ogbomoso | Nigeria | ||
| 8 | State Hospital | Oyo | Nigeria | ||
| 9 | Ayub Teaching Hospital (Unit A) | Abbottabad | Pakistan | ||
| 10 | Ayub Teaching Hospital Unit B | Abbottabad | Pakistan | ||
| 11 | Bahawalpur Victoria Hospital | Bahawalpur | Pakistan | ||
| 12 | Aziz Bhatti Teaching Hospital | Gujrat | Pakistan | ||
| 13 | MCH PIMS | Islamabad | Pakistan | ||
| 14 | Military Hospital | Islamabad | Pakistan | ||
| 15 | Civil Hospital | Karachi | Pakistan | ||
| 16 | Jinnah Postgraduate Medical Centre | Karachi | Pakistan | ||
| 17 | Jinnah Hospital | Lahore | Pakistan | ||
| 18 | Services Hospital | Lahore | Pakistan | ||
| 19 | Sir Ganga Ram Hospital | Lahore | Pakistan | ||
| 20 | Chandka SMBBMU Sheikh Zaid Woman Hospital | Larkana | Pakistan | ||
| 21 | Nishtar Hospital | Multan | Pakistan | ||
| 22 | Bolan Medical Centre | Quetta | Pakistan | ||
| 23 | Benazir Bhutto Shaheed Hospital | Rawalpindi | Pakistan | ||
| 24 | Federal Government Polyclinic | Rawalpindi | Pakistan | ||
| 25 | Holy Family Hospital | Rawalpindi | Pakistan | ||
| 26 | Mount Meru Regional Referral Hospital | Arusha | Tanzania | ||
| 27 | Amana Regional Referral Hospital, | Dar Es Salaam | Tanzania | ||
| 28 | Muhimbili National Hospital | Dar Es Salaam | Tanzania | ||
| 29 | Temeke Regional Referral Hospital | Dar Es Salaam | Tanzania | ||
| 30 | Dodoma Regional Referral Hospital | Dodoma | Tanzania | ||
| 31 | Makole Hospital | Dodoma | Tanzania | ||
| 32 | Tumbi Regional Referral Hospital, Kibaha | Kibaha | Tanzania | ||
| 33 | Mwananyamala Regional Referral Hospital | Kinondoni | Tanzania | ||
| 34 | Mbeya Zonal Referral Hospital | Mbeya | Tanzania | ||
| 35 | Women and Newborn Hospital | Lusaka | Zambia |
Sponsors and Collaborators
- London School of Hygiene and Tropical Medicine
- Wellcome Trust
- Bill and Melinda Gates Foundation
Investigators
- Study Chair: 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
- Principal Investigator: Rizwana Chaudhri, National Coordinating Investigator, Rawalpindi Medical University, Pakistan
- Principal Investigator: Nike Bello, National Coordinating Investigator, University College Hospital, Nigeria
- Principal Investigator: Bellington Vwalika, National Coordinating Investigator, Zambia
- Principal Investigator: Projestine Muganyizi, National Coordinating Investigator, Tanzania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WOMAN_2
- 03475342