One of the most heart-wrenching public health problems facing the world has been the large number of women who die during or after childbirth despite all our medical progress. Melinda Gates has called the issue one of her top priorities and committed more than $1.5 billion from her family’s foundation to the cause. Countless scientists have explored the issue from every angle.
But could part of the solution be simpler than we imagined?
The results of a remarkable clinical trial released Wednesday in the journal Lancet suggest that a single injection of an old drug — and one that costs less than $1 a dose — may be able to save tens of thousands of lives each year.
The study, conducted in 193 hospitals in 21 countries, involved 20,000 women who were undergoing one of the most life-threatening medical complications: postpartum hemorrhage. Giving birth takes a brutal toll on a woman's body, and many things can go wrong along the way — a tear in the vagina or birth canal, a rupture of the cervix, a placenta that is stuck to the womb and doesn't separate properly. In some cases, women experience a coagulation problem in which there is no obvious injury but there is uncontrollable bleeding. This bleeding is the leading cause of maternal mortality around the world. An estimated 14 million women experience postpartum hemorrhage, and more than 100,000 die from it per year.
In the study, known as the WOMAN (or World Maternal Antifibrinolytic) Trial, patients were randomized to receive either a placebo or tranexamic acid (TXA), which helps the blood to clot. The treatment, given intravenously, was used alongside other actions that emergency doctors would normally take to try to stop such bleeding. The trial was double-blind, meaning neither the doctors and researchers nor the patients knew what they got.
In analyzing the outcomes of the women, the research team, co-led by the London School of Hygiene and Tropical Medicine’s Ian Roberts, found that the risk of death from bleeding was reduced by 20 percent for the women who got tranexamic compared with those who got nothing. If the medicine was given quickly, within three hours of the start of bleeding, the results were even more promising — with a 30 percent reduction in the risk of death.
TXA was discovered more than 50 years ago by a Japanese doctor, Utako Okamoto, but TXA's value wasn’t recognized until relatively recently. In 2010, another large trial — known as CRASH-2 — that involved victims of traffic accidents, shootings and land mines who were bleeding out showed that TXA could reduce the risk of death in those trauma patients by 15 percent.
Paramedics in some countries carry the injection, and the World Health Organization has added it to its list of essential medicines that should be available to everyone and that form the basis of national drug policy in countries across the world.
Roberts, who also worked on the trauma trial, said TXA's under-appreciation for so long underscores how the global system of pharmaceutical discovery and development is broken. If it wasn’t for Gates and other donors like the Wellcome Trust getting involved and funding the postpartum-bleeding trial, it may have never gotten off the ground.
“There has been a market failure with this drug for a long time,” Roberts said. “We didn’t reap its humanitarian benefit because there was no sort of financial incentive to do so.”
Wellcome Trust senior partner Tim Knott said the trial “stands to make a critical difference in preventing women dying after childbirth.”
Not only is TXA cheap, it doesn’t need to be refrigerated, making it easy to transport and store. The main drawback, Roberts said, is that many women in the developing world give birth in remote areas assisted only by a midwife or someone else who may not be trained to give an intravenous injection. He said the researchers' next step is to look at formulations of TXA that can have a similar effect but can be given in pill or other form so someone with little training can administer it.
The WHO recommends that TXA be given if other efforts to control bleeding fail, but Roberts said the study suggests that the timeline for the drug be accelerated, especially in developing countries, so that doctors give it as soon as the bleeding begins.
“The trial data show women die really soon after onset,” he said. “If a woman has a postpartum hemorrhage in Washington, D.C., the hospital will likely have a lot of blood in the blood bank and lots of tools to keep a woman stable while they try one thing and then another. But in Africa, a woman can die within the hour or certainly within that day if the bleeding is not controlled."