Steroids harmed community-acquired pneumonia patients? (REMAP-CAP)

Results contradict the new steroids-for-most critical care paradigm

In 2024, the leading U.S. critical care society advised that most patients with critical illness—including severe community-acquired pneumonia (CAP), septic shock, and acute respiratory distress syndrome (ARDS)—should receive corticosteroids.

This was based on what seemed to be an abundance of evidence, some of the most convincing of which was the CAPE COD trial. Among 800 patients at 31 French ICUs with severe pneumonia (excluding septic shock and influenza patients), those randomized to receive adjunctive hydrocortisone had a dramatic ~50% relative reduction in mortality, and a ~6% absolute reduction in mortality.

REMAP-CAP Throws a Curve

REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-Acquired Pneumonia) is a randomized trial “platform”, i.e., a framework to continuously enroll subjects with pneumonia and test various questions, without the need to design a new trial for each new question.

REMAP-CAP enrolls patients at hundreds of sites in ~25 countries, mostly in Europe. Its Bayseian “adaptive” design directs enrollment dynamically in a pseudo-randomized fashion, and its data are analyzed and reported as posterior probabilities rather than in the confidence intervals and p-values of conventional frequentist trials.

In 2020, REMAP-CAP added to the signal that steroids (hydrocortisone) appeared to be beneficial in patients with severe Covid pneumonia. Dexamethasone soon became standard therapy for severe Covid, based on the frequentist RECOVERY trial.

The REMAP-CAP platform continued to “randomize” community-acquired pneumonia patients without Covid to hydrocortisone (50 mg I.V. every 6 hours for 7 days) through 2023.

(We’ll put scare quotes around “randomize” as the platform does not follow the familiar conventions of frequentist trials, often allocating patients to arms unequally and in variable ratios according to its own internal mathematical logic.)

Did Steroids Harm Severe CAP Patients?