An inexpensive and widely available drug could save the lives of one in three mothers who would otherwise bleed to death after childbirth, according to a major study published in The Lancet. More than 300 women from five hospitals in Bangladesh took part in the global trial, which included 20,000 women in 21 countries, mainly in Africa and Asia, but also in the UK and elsewhere.
The drug, called tranexamic acid (TXA), works by stopping blood clots from breaking down. The study found that death due to bleeding was reduced by 31 percent if the treatment was given within three hours. The findings also show it reduced the need for urgent surgery to control bleeding (laparotomy) by more than a third (36 percent).
Severe bleeding after childbirth (known as post-partum haemorrhage or PPH) is the leading cause of maternal death worldwide. More than 100,000 women globally die each year from the condition, but this clot-stabilising drug has the potential to reduce the number substantially. According to the World Health Organization and partners, Bangladesh has a maternal mortality rate of 176 deaths per every 100,000 live births. In 2015 there were an estimated 5,500 maternal deaths in the country, and postpartum haemorrhage was the single biggest cause.
New strides in science
The London School of Hygiene & Tropical Medicine coordinated the study, which is called The WOMAN (World Maternal Antifibrinolytic) Trial. It was funded by The Wellcome Trust and UK Department of Health through the Health Innovation Challenge Fund, and the Bill & Melinda Gates Foundation.
Dr Kaosar Afsana, Director of Health, Nutrition and Population at BRAC (a leading international development organisation based in Bangladesh), is part of the WOMAN Trial committee. She said: "Post-partum haemorrhage is the prime cause of maternal deaths in Bangladesh. I am so excited about the results of the Woman Trial. Timely use of simple tranexamic acid will save many lives of mothers in Bangladesh by averting unnecessary maternal deaths, even in remote health facilities where there are no obstetricians or trained physicians."
The results show that of the women given tranexamic acid within three hours, 89 died from bleeding compared with 127 given placebo (in addition to standard care). The researchers found no side effects from the drug for either mothers or babies. These findings provide the first comprehensive evidence on using tranexamic acid for post-partum haemorrhage and suggest it should be used as a frontline treatment.
Haleema Shakur, Associate Professor of Clinical Trials at the London School of Hygiene & Tropical Medicine and Project Director of the WOMAN Trial, said: “We now have important evidence that the early use of tranexamic acid can save women’s lives and ensure more children grow up with a mother. It’s safe, affordable and easy to administer, and we hope that doctors will use it as early as possible following the onset of severe bleeding after childbirth.”
An old remedy finally being put to use
Tranexamic acid was invented in the 1960s by a Japanese husband and wife research team, Shosuke and Utako Okamoto. Ian Roberts, Professor of Clinical Trials at the London School of Hygiene & Tropical Medicine, who co-led the study, said: “The researchers who invented tranexamic acid more than 50 years ago hoped it would reduce deaths from post-partum haemorrhage, but they couldn’t persuade obstetricians at the time to conduct a trial. Now we finally have these results that we hope can help save women’s lives around the world.”
Almost all of the deaths from postpartum haemorrhage are in low- and middle-income countries. Although giving birth in a health facility increases the chance of surviving post-partum haemorrhage, women still die from the condition even within hospitals.
Tim Knott, Senior Partner in Innovations at Wellcome Trust, said: “Globally, severe bleeding in childbirth remains one of the main causes of maternal death – with alarming numbers of women dying in many low- and middle-income countries. The WOMAN Trial team undertook a hugely important and incredibly ambitious study. Their work stands to make a critical difference in preventing women dying after childbirth.”
While the WOMAN Trial found that tranexamic acid significantly reduced death due to bleeding, it did not prevent hysterectomy. The researchers say this is because in low- and middle-income countries where blood supplies are limited, a hysterectomy is sometimes carried out immediately after the onset of very severe post-partum haemorrhage to save the mother’s life. This means there is no time for tranexamic acid to have an effect.
The study builds on previous research involving 20,000 trauma patients, which showed that tranexamic reduced deaths due to bleeding by almost a third if given within three hours.
Current World Health Organization guidelines, based on the previous trauma research, recommend the use of tranexamic acid in post-partum haemorrhage as a subsequent treatment option if uterotonics (drugs to induce contractions) fail to control the bleeding, or if the bleeding is thought to be due to trauma. Post-partum haemorrhage is defined as a blood loss of more than 500ml within 24 hours of giving birth.