This is the second “steroids for pneumonia” trial published in the last few weeks. The last trial, enrolling 785 patients with community-acquired pneumonia, showed a small – but potentially relevant – reduction in inpatient length-of-stay. No differences were noted with respect to mortality or treatment failure.
This trial, however, is a bit different. In an effort to maximize the theoretical mortality reduction associated with steroid use in pneumonia, these authors targeted therapy specifically at those in the highest pneumonia severity risk categories and required a CRP >150 mg/L. Patients were then randomized to 0.5 mg/kg twice daily of intravenous methylprednisolone or placebo. The primary outcome was “treatment failure”, which was composed of two definitions – one specifically for early deterioration and one for late deterioration.
At face value – the results are excellent. There was 31% failure rate in the 59 patients in the placebo group, compared with 13% of the 61 patients in the methylprednisolone group. Deaths were 10% in the methylprednisolone group and 15% for placebo, and few adverse events occurred in either group – these differences, however, did not reach statistical significance due to the small sample size.
But this trial is essentially noise, full of baseline confounders and inconsistencies. To start, simply, note each center enrolled, on average, one patient every-other month for eight years – only managing to screen 519 total patients with pneumonia for eligibility over the course of the trial. This does not reflect a well-executed trial infrastructure. An excess of 11% of placebo patients were admitted to the ICU, reflecting in part a 20% excess of placebo patients with shock as part of their initial presentation. Shock and multiple organ failure was the major cause of death in the placebo group, compared with disease progression in the steroid cohort.
Furthermore, 40% of the placebo patients presenting with shock did not receive antibiotics within 4 hours of arrival. Causative organisms were detected for 51% of the steroid cohort, compared with 30% of the placebo group – with 21% of the steroid cohort having a “respiratory virus” compared with 8% in the placebo group. Antibiotic use was also odd, with the prevailing choice being ceftriaxone plus levofloxacin, rather than the typical ceftriaxone + azithromycin combination used for CAP.
How this managed to get published in one of the supposedly pre-eminent medicine journals is beyond me. With only 120 patients, all the substantial absolute differences in baseline characteristics and care heavily distort the overall results. Mostly, unfortunately, it looks like placebo patients were sicker and received less-adequate initial care – and everything measured in this small trial is suspect as a result.
“Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response”
http://www.ncbi.nlm.nih.gov/pubmed/25688779