Brain injuries account for more than 2 million hospitalizations or emergency room visits each year in the United States and often cause major disabilities. Roadside bombs have increased the number of troops suffering closed-head injuries, too.
Some drugs can reduce symptoms, such as swelling, but none are known to improve long-term recovery and prevent disability. Work in animals and two very encouraging small trials in people suggested progesterone might.
It is a female sex hormone that is thought to protect nerves and brain cells in a variety of ways, including curbing inflammation that causes swelling after an injury.
The two new studies were meant to be definitive tests.
In one, funded by the National Institutes of Health and led by doctors at Emory University and Grady Memorial Hospital in Atlanta, dozens of trauma centres around the U.S. aimed to enrol 1,140 patients with moderate to severe brain injuries — mostly car crash victims.
They were given infusions of progesterone or a dummy solution for four days, starting within four hours of injury. Independent monitors stopped the study after 882 patients were enrolled and the treatment seemed futile. Those given progesterone also were more likely to suffer phlebitis, or inflammation in the legs and arms that can lead to dangerous clots.
"It was an absolute, complete failure," said Emory's Dr. David Wright, who said he was "stunned" at the result. "We had all hoped this was going to move the field forward," and now patients are left "with very little hope."
The second study involved 1,195 severe brain injury patients in 21 countries, treated within eight hours of injury for five days. Six months later, rates of death and disability were similar in those given a placebo or a progesterone solution made by BHR Pharma, the company that sponsored that study. It was led by doctors at the Hofstra North Shore-LIJ School of Medicine in New York.
Results of both studies were published online Wednesday by the New England Journal of Medicine.
They may have reflected overly optimistic assumptions from small, earlier tests of progesterone and set a high bar for success, Dr. Lee Schwamm, stroke chief at Massachusetts General Hospital, wrote in a commentary in the journal.
"The opportunity cost of these failed studies is high," he wrote. In the future, researchers should do more early testing and pool results so that only the most promising treatments move into expensive, late-stage trials, he wrote.
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