Tranexamic Acid for the Prevention of Postpartum Bleeding in Women With Anaemia: an International, Randomised, Double-blind, Placebo Controlled Trial.

World Maternal Antifibrinolytic Trial_2

Sponsors

Lead sponsor: London School of Hygiene and Tropical Medicine

Collaborator: Wellcome Trust
Bill and Melinda Gates Foundation

Source 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.

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.

Overall Status Recruiting
Start Date August 24, 2019
Completion Date August 2022
Primary Completion Date June 2022
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Postpartum Haemorrhage (cause will be described) 24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier
Secondary Outcome
Measure Time Frame
Postpartum blood loss 24 hours after administration of the trial medication or at discharge from hospital, whichever is earlier
Haemaglobin 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
Expected side effects of trial medication Day 42 or discharge from hospital, whichever is earlier
Exercise tolerance Day 42 or discharge from hospital, whichever is earlier
Interventions to control primary postpartum haemorrhage (medical and surgical) Day 42 or discharge from hospital, whichever is earlier
Receipt of blood product transfusion Day 42 or discharge of mother from hospital, whichever is earlier
Vascular occlusive events Day 42 or discharge from hospital, whichever is earlier
Symptoms of anaemia Day 42 or discharge of mother from hospital, whichever is earlier
Organ disfunction Day 42 or discharge from hospital, whichever is earlier
Sepsis Day 42 or discharge from hospital, whichever is earlier
In hospital death Day 42
Length of hospital stay. Day 42 or discharge from hospital, whichever is earlier
Admission to and time spent in higher level facility Day 42 or discharge from hospital, whichever is earlier
Status of baby/ies Day 42 or discharge of mother from hospital, whichever is earlier
Thromboembolic events in breastfed babies Day 42 or discharge of mother from hospital, whichever is earlier
Adverse events Day 42
Enrollment 10000
Condition
Intervention

Intervention type: Drug

Intervention name: Tranexamic Acid

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

Arm group label: Tranexamic acid

Intervention type: Other

Intervention name: Placebo

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

Arm group label: Placebo

Other name: (Sodium Chloride 0.9%)

Eligibility

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.

Gender: Female

Gender based: Yes

Gender description: Women who have given birth

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Overall Official
Overall Contact

Last name: Haleema Shakur-Still, MSc

Phone: +44(0)20-7958-8113

Email: [email protected]

Location
facility status contact
Ayub Teaching Hospital | Abbottabad, Pakistan Recruiting A Abbasi
Bahawalpur Victoria Hospital | Bahawalpur, Pakistan Recruiting N Fatima
Aziz Bhatti Teaching Hospital | Gujrat, Pakistan Recruiting S Hussein
MCH PIMS | Islamabad, Pakistan Recruiting S Batool
Military Hospital | Islamabad, Pakistan Recruiting S Baqai
Civil Hospital | Karachi, Pakistan Recruiting F Perveen
Jinnah Postgraduate Medical Centre | Karachi, Pakistan Recruiting H Yasmin
Jinnah Hospital | Lahore, Pakistan Recruiting A Tajammul
Services Hospital | Lahore, Pakistan Recruiting R Sohail
Sir Ganga Ram Hospital | Lahore, Pakistan Recruiting S Humayun
Chandka SMBBMU Sheikh Zaid Woman Hospital | Larkana, Pakistan Recruiting S Magsi
Nishtar Hospital | Multan, Pakistan Recruiting H Quddusi
Bolan Medical Centre | Quetta, Pakistan Recruiting N Ehsan
Benazir Bhutto Shaheed Hospital | Rawalpindi, Pakistan Recruiting H Noreen
Federal Government Polyclinic | Rawalpindi, Pakistan Recruiting N Israr
Holy Family Hospital | Rawalpindi, Pakistan Recruiting S Sial
Women and Newborn Hospital | Lusaka, Zambia Recruiting K Lubeya
Location Countries

Pakistan

Zambia

Verification Date

February 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Tranexamic acid

Arm group type: Active Comparator

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

Arm group label: Placebo

Arm group type: Placebo Comparator

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

Acronym WOMAN-2
Patient Data Yes
Study Design Info

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.

Primary purpose: Prevention

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.

Source: ClinicalTrials.gov