74: REMAP-CAP Results: Oseltamivir in Critically-Ill Influenza Patients

In this episode of "In the Interim…", Dr. Scott Berry speaks with Dr. Srinivas Murthy, Dr. Thomas Hills, and Dr. Lindsay Berry about the REMAP-CAP trial results on oseltamivir in critically ill influenza patients. The trial used a Bayesian covariate-adjusted platform design and found oseltamivir was not effective at reducing 90-day mortality with a “98% and 99% probability of harm in 90-day mortality” compared to control. Covariate adjustment addressed baseline and site variation. Subgroup analyses showed greater harm in patients with higher illness severity. Sensitivity analyses using alternative neutral, optimistic, and pessimistic priors produced important scientific exploration of the results. No evidence was found for benefit over control in any subgroup.

The discussion highlights the first randomized, controlled evidence in this patient group, contrasting prior observational studies and clinical guidelines. A mechanism of harm remains unclear. REMAP-CAP is continuing enrollment in moderate severity and pediatric cohorts to further examine population-specific effects. The episode also addresses the broader challenges of trial design and interpretation in acute care research, the limitations of nonrandomized evidence, and the importance of ongoing Bayesian analyses and transparent reporting.

Key Highlights

• Pre-print is available: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=7172531

• REMAP-CAP platform trial, Bayesian logistic regression, covariate adjustment

• Oseltamivir arms: statistical trigger for inferiority, “98 and 99% probability of harm”

• Greater harm in sicker subgroups, consistent results across sensitivity analyses

• Ongoing arms: moderate severity and pediatric cohorts, mechanistic questions unresolved

• Context: limitations of previous historical data studies, clinical practice impact, future research directions