Giving doses of the steroid hydrocortisone to patients with severe pneumonia cut the risk of death by about half, according to a study released Tuesday.
In the study, researchers funded by the French Ministry of Health randomly assigned 800 patients who had been placed in the intensive care unit to receive either hydrocortisone or a placebo. In the hydrocortisone group, about 6% of patients died within 28 days. In the placebo group, about 12% died in the same time frame. There was an absolute reduction in deaths of 5.6%, which was statistically significant.
“This study should change our care practices,” said Pierre-François Dequin, a professor at the University of Tours and the study’s lead author. “It is the first to show a survival benefit that has been mentioned for a few years but never confirmed.”
The results were published in the New England Journal of Medicine.
Most pharmaceutical studies are of medicines that are still protected by patents, and are funded by those medicines’ manufacturers. This study is an exception: a government-funded randomized trial of an inexpensive generic drug.
But David Boulware, an infectious disease physician at the University of Minnesota Medical School, said the results should “fundamentally change” the way doctors treat patients with community-acquired pneumonia who need to be cared for in the ICU.
The results will also “challenge” current treatment guidelines, which advise against the use of corticosteroids in community-acquired pneumonia because they can blunt the immune system, said Paul Sax, clinical director of the division of infectious disease at Brigham and Women’s Hospital in Boston.
In the study, hydrocortisone was given for either four or eight days at a dose of 200 milligrams per day, depending on whether patients showed improvement.
There were other apparent benefits. Among the 442 patients who were not on mechanical ventilators, 65, or 29.5%, of those who received placebo needed to be intubated. By comparison, 40, or 18%, of those receiving hydrocortisone were intubated — a 41% reduction in risk. There was also a 40% reduction in the number of patients who needed drugs called vasopressors added to their treatment.
Whether and when corticosteroids should be used to treat pneumonia has been a matter of debate among doctors for some time. Another steroid, dexamethasone, was one of the first drugs found to reduce death from Covid-19 in a similar setting. Dequin led another study of steroids in Covid using hydrocortisone, but it was stopped because of dexamethasone’s success.
The pneumonia study was conducted during the pandemic, but Dequin said it was unlikely patients had Covid-19 pneumonia. To make sure this did not affect the results, statisticians conducted an analysis comparing the results before and after the pandemic began and did not see a difference in outcomes.
However, the study did exclude patients with influenza, because there is some evidence steroids might be harmful there. At the current time, Dequin said, doctors should not start steroids if patients have influenza and should stop them if influenza is detected.
Andre Kalil, a professor at the University of Nebraska Medical Center, noted that the results contradict a 600-person randomized trial that used a different steroid, methylprednisolone — and that there have previously been a mix of positive and negative results for steroid drugs in severe pneumonia. The differences could be the result of different dosing strategies, different levels of antibiotic use, and differences in how severe pneumonia itself is diagnosed and defined.
Still, he said, the new data are part of a growing body of evidence that suggests there are benefits to the “selective and judicious” use of hydrocortisone in patients admitted to the ICU who have risk factors like being over 65 and low blood oxygen levels. Future studies may be needed to further assess the safety of steroids, which have been linked to sepsis, bleeding, and neuropsychiatric side effects, Kalil said.