Hydrocortisone lowers risk from severe pneumonia, study finds
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Key takeaways:
- Patients with severe community-acquired pneumonia treated with hydrocortisone had a lower incidence of death 28 days after treatment than those receiving placebo.
- New phase 3 trial reaffirms previous findings.
People with severe community-acquired pneumonia who were treated with hydrocortisone had a lower risk for death 28 days after diagnosis compared with those who received placebo, a phase 3 trial found.
Worldwide, community-acquired pneumonia (CAP) caused 489 million lower respiratory infections in 2019, according to the authors of the new study, which was published in The New England Journal of Medicine. In the United States, 1.5 million adults are hospitalized with CAP per year and about 50,000 die from the infection, making it the ninth leading killer in the nation, the authors reported.
A 2015 meta-analysis of data collected between 2010 and 2015 showed measurable decreases in mortality, a need for mechanical ventilation and duration of hospital stay among pneumonia patients treated with corticosteroids.
Researchers in that trial concluded that “larger pragmatic trials” could improve the clinical certainty of using corticosteroids for pneumonia treatment and help elucidate the potential risks and side effects.
“Few large, multicenter trials have evaluated glucocorticoids in patients with severe CAP who have been admitted to the ICU,” Pierre-François Dequin, MD, PhD, a professor and hospital practitioner at the University of Tours in France, and colleagues wrote in the new study.
CAPE COD was a phase 3, multicenter, double-blind, randomized, controlled trial. Dequin and colleagues assessed 5,948 patients from Oct. 28, 2015, to March 11, 2020, enrolling 795 patients in the study, assigning 400 to a hydrocortisone group and 395 to a placebo group.
By day 28, 25 of 400 patients in the hydrocortisone group (6.2%) had died, whereas 47 in the placebo group died (11.9%). By day 90, the researchers reported mortality had risen to 9.3% in the hydrocortisone group and 14.7% in the placebo group, maintaining a roughly 5-percentage point difference.
Among participants in the trial group, hydrocortisone was not linked to increases in hospital-acquired infections or gastrointestinal bleeding. Patients in the hydrocortisone group received higher doses of insulin in their first week of treatment to counter an expected increased incidence of hyperglycemia.
“The results appeared to be consistent across important subgroups,” Dequin and colleagues wrote. “Our data do not indicate any particular safety issues, including no between-group difference in the occurrence of hospital-acquired infections.”
References:
- Dequin P-F, et al. N Eng J Med. 2023;doi:10.1056/NEJMoa2215145.
- Siemieniuk R, et al. Ann Intern Med. 2015;doi:10.7326/M15-0715.
Perspective
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The evaluation of systemic glucocorticoids for the treatment of severe CAP has a long and sometimes contradictory history. Although the CAPE COD trial by Dequin and colleagues has attracted a great deal of attention, it is far from the first such study. Four features strike me as significant about this study.
First, we have grown comfortable with the use of glucocorticoids for severe respiratory infections since the publication of the RECOVERY trial. I suspect that this increased comfort will lead to more widespread adoption of hydrocortisone for severe CAP than we have seen before.
Second, the evidence of benefit for hydrocortisone seems more robust in patients with a C-reactive protein level of more than 15 mg/dL, but I would put more stock in a patient’s physiology (eg, the degree of hypoxemia and other signs of clinical instability) than in the results of a single blood test.
Third, the presence of influenza as an exclusion criterion may have strengthened the results. Glucocorticoids for severe influenza may be harmful, although the quality of this evidence is uncertain.
And fourth, hydrocortisone was safe, with a nonsignificant decrease in ventilator-associated pneumonia, bloodstream infections or gastrointestinal bleeding compared with placebo. Insulin requirements were understandably higher in the hydrocortisone group, but this is an easily managed problem.
In my own practice, I anticipate using hydrocortisone for adult inpatients with severe CAP in the absence of influenza in the future.
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