People who suffer serious brain injuries will be given infusions of a sex hormone to investigate whether it can save lives and reduce patients' disabilities.
The clinical trial, which starts in the US next month, follows a small-scale study of 100 patients which found that giving progesterone soon after a brain injury halved the death rate and improved their ability to recover. These promising results prompted doctors to launch a large-scale trial involving 17 accident and emergency departments at hospitals in 15 states.
The hospitals will randomly assign 1,140 patients who arrive at A&E within 11 hours of injury to receive either a three-day course of progesterone infusions or a placebo. The trial is the final step before application for a licence to use the hormone as a standard treatment for brain injury. Progesterone is cheap and already approved for other medical uses.
If hormone infusion works as well as doctors hope, it will become the first new treatment for three decades to boost patients' chances of surviving and recovering from a major brain injury.
Speaking about the trial, David Wright, professor of emergency medicine at Emory University School of Medicine in Atlanta, Georgia, said: "This could transform the way we care for head injury patients. It could be a dramatic improvement. [There has been] no treatment in 30 years … and now we're on the brink of having something."
Progesterone plays a role in female fertility, but it is found in small quantities in the brains of both sexes, where it is crucial for the healthy development of neurons.
Doctors identified progesterone as a potential treatment after noticing that women responded more strongly to therapy and recovered better after brain injury or stroke than did men. Donald Stein, a professor of emergency medicine at Emory who is involved in the study, said the team discovered that progesterone protects cells and tissues just as it does during the early stages of pregnancy.
According to the brain injury association Headway, more than a million people in the UK visit hospital with a head trauma every year, and around 135,000 are admitted owing to the severity of their injury. Half a million people are living with long-term disabilities following brain injuries, and roughly half of all deaths in people under 40 are owing to such accidents.
Wright described the trial, which will run for three to six years, at a meeting of the American Association for the Advancement of Science in San Diego today. Known as proTECT III (for progesterone for traumatic brain injury – experimental clinical treatment), the trial will be run from Atlanta's Grady Memorial hospital.
"With such promising success in laboratory testing and in our previous clinical trial, we hope to conclude in this national trial that progesterone, along with standard medical trauma care, works better than standard medical care alone in reducing brain damage," he said.
Because the infusions are believed to be most effective if given within 11 hours of patients receiving their injury, Wright said it will not always be possible to obtain consent to take part in the trial from patients' next of kin. The US drug regulator, the Food and Drug Administration, has drawn up special rules to allow trials of emergency medical treatments to go ahead without consent.
A progesterone trial involving 159 patients with serious brain injuries was conducted in China two years ago. Weiqi Han at Zhejian University gave the hormone intravenously to 82 patients and a placebo to the remainder. Out of the 40 patients who died of their injuries, 32% had received a placebo infusion, while only 18% had been given progesterone.
Six months after treatment, the patients who received progesterone had recovered better than those who received placebo, suggesting their brains had not been as severely damaged. Doctors who assessed the patients found that 58% who received progesterone had made a good recovery, compared with only 42% who had received placebo.
