Deconstructing the Treatment Effect of Remdesivir in the Adaptive COVID-19 Treatment Trial-1: Implications for Critical Care Resource Utilization.

Background The Adaptive COVID-19 Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death. Methods We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1. We developed competing risks models that estimate the effect of remdesivir therapy on cumulative incidence of clinical improvement and deterioration, and multistate models that utilize the entirety of each patient's clinical course to characterize the effect of remdesivir on progression along the 4 pathways above. Results Based on a competing risks analysis, remdesivir reduced clinical deterioration (hazard ratio, 0.73; 95% CI, 0.59-0.91) and increased clinical improvement (hazard ratio, 1.22; 95% CI, 1.08, 1.39) relative to baseline. Our multistate models indicate that remdesivir inhibits worsening to ordinal scores of greater clinical severity among patients on room air or low-flow oxygen (hazard ratio, 0.74; 95% CI, 0.57-0.94) and among patients receiving mechanical ventilation or high-flow oxygen/noninvasive positive-pressure ventilation (hazard ratio, 0.73; 95% CI, 0.53-1.00) at baseline. We also find that remdesivir reduces expected intensive care respiratory therapy utilization among patients not mechanically ventilated at baseline. Conclusions Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.