International Women’s Day is a celebration of women’s achievements and an opportunity to advocate for gender equality. This year’s theme ‘accelerate action,’ aligns strongly with the goals of the WOMAN Trials which are advancing evidence and action to reduce maternal deaths from haemorrhaging and to improve maternal health.
Discovery of a lifesaving drug
Over sixty years ago, the brilliant Dr Utako Okamoto made a discovery that had the potential to save millions of lives – yet this discovery remains underused and undervalued.
Dr Utako Okamoto, alongside her husband Dr Shosuke Okamoto, invented tranexamic acid (TXA), a drug that reduces excessive bleeding. After its initial discovery in 1962, it took decades before the drug was widely recognised to be an effective, safe and easy to use drug. Part of the reason for this was that a discovery presented by a woman and aimed at saving the lives of women after childbirth, was not taken seriously in the male-dominated field of medical science.
However, even today, issues such as a lack of awareness among healthcare professionals and a lack of affordability and accessibility of TXA in low- and middle- income countries (LMICs) mean it remains underused.
Here at the Clinical Trials Unit at the London School of Hygiene & Tropical Medicine, trial teams have been investigating TXA in surgical and traumatic bleeding for over two decades. Through the CRASH Trials, the team has produced evidence that TXA can reduce the risk of dying from bleeding by a third in trauma patients.
Could TXA be used to treat life-threatening bleeding after birth?
Life-threatening bleeding after birth, or postpartum haemorrhage (PPH), is the leading cause of maternal death, killing over 70,000 mothers each year, mostly in LMICs.
Following the CRASH-2 Trial, the team realised the potential of Dr Utako’s discovery in possibly saving thousands of women’s lives globally and set to investigate its use to treat PPH – leading to the start of the WOMAN Trials.
The WOMAN Trial made major steps in understanding the role TXA could play in maternal healthcare, finding that TXA could reduce death due to bleeding after birth by about a third when treatment was given within three hours. Six months after the WOMAN Trial results were published, the World Health Organization updated its guidelines to include the use of TXA for treatment of PPH.
This led to the WOMAN-2 Trial, which investigated if giving TXA to women with moderate and severe anaemia at cord-clamping could prevent PPH. The trial team published two papers in October last year, which revealed important evidence on the effects of TXA on PPH after childbirth, as well as highlighting the hugely negative impact that moderate and severe anaemia have on pregnant women and their babies.
Failings in maternal healthcare
While the WOMAN Trials initially began to try to prevent women bleeding to death from childbirth, this work has subsequently led them to uncover fundamental risk factors and the failings in maternal healthcare in addressing these.
The WOMAN-2 Trial data revealed that anaemic women have an increased risk of PPH and death, as well as an increased risk of serious complications, including stillbirth and premature birth.
In sub-Saharan Africa and south Asia half of all pregnant women are anaemic. Despite anaemia being a detectable and treatable condition, many pregnant women continue to give birth while anaemic, some severely anaemic, and therefore face potential life-threatening complications for both them and their babies.
This isn’t just a problem in pregnancy, many women are anaemic before, during and after pregnancy. The issue is systemic and without proper nutrition, reducing iron loss during menstruation, regular pre- and postnatal check-ups and accessible healthcare, women remain at risk.
The WOMAN Trials emphasise that maternal health emergencies should not simply be treated as they arise, they should be prevented from ever happening.
Eni Balogun, Senior Trial Manager – Research Fellow, Global Health Trials Group at the London School of Hygiene & Tropical Medicine, said: “Women’s health must remain a global priority, not an afterthought. We need to prioritise women’s healthcare, increase investment into women’s health research and ensure barriers to the inclusion of women in medical research are overcome.
“By doing so, we can move beyond research and into action, drive policy and health system changes and ultimately, improve maternal health.”
Accelerating Action
The WOMAN Trials now shifts its focus to consider how we can treat women and their health before pregnancy, to reduce high levels of anaemia and prevent critical incidents of PPH and other serious outcomes, including death from anaemic heart failure, stillbirths and pre-term births. The WOMAN-3 Trial, due to start recruiting this year, will investigate if giving TXA during menstruation in adult women with anaemia can improve their anaemia.
Continued changes in practice are also needed to ensure TXA is accessible and available for the women who need it. Advocacy among clinicians, so they know about the drug and how to use it, is critical to support an uptake in its use. Making sure that TXA is available in as many hospitals, clinics and healthcare facilities as possible will mean more women can access the drug when needed.
The I’M WOMAN trial is currently assessing the effects of intramuscular TXA in women at increased risk of PPH. If possible, this could mean women giving birth outside of hospitals could also have access to TXA – intramuscular administration requires less training than intravenous administration of TXA and therefore more healthcare workers, including those working in the community, could treat women with the drug.
Haleema Shakur-Still, Emeritus Professor of Global Health Clinical Trials at the London School of Hygiene & Tropical Medicine, said: “The lifesaving drug TXA, invented over 60 years ago by Dr Utako Okamoto, has the potential to prevent thousands of women dying from life-threatening bleeding every year. We must ensure it reaches every woman who needs it in every country around the world.
“On International Women’s Day, let us consider the progress made in women’s healthcare so far, and accelerate action to ensure more is done to see health equity.”