Awake Prone Positioning Strategy for Nonintubated Hypoxic Patients with COVID-19: A Pilot Trial with Embedded Implementation Evaluation.

Prone positioning is an appealing therapeutic strategy for nonintubated hypoxic patients with coronavirus disease (COVID-19), but its effectiveness remains to be established in randomized controlled trials. To identify contextual factors relevant to the conduct of a definitive clinical trial evaluating a prone positioning strategy for nonintubated hypoxic patients with COVID-19. We conducted a cluster randomized pilot trial at a quaternary care teaching hospital. Five inpatient medical service teams were randomly allocated to two treatment arms: ) usual care (UC), consisting of current, standard management of hypoxia and COVID-19; or ) the Awake Prone Positioning Strategy (APPS) plus UC. Included patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing or suspected COVID-19 pneumonia and oxygen saturation less than 93% or new oxygen requirement of 3 L per minute or greater and no contraindications to prone positioning. Oxygenation measures were collected within 48 hours of eligibility and included nadir oxygen saturation to fraction of inspired oxygen (S/F) ratio and time spent with S/F ratio less than 315. Concurrently, we conducted an embedded implementation evaluation using semistructured interviews with clinician and patient participants to determine contextual factors relevant to the successful conduct of a future clinical trial. The primary outcomes were drawn from an implementation science framework including acceptability, adoption, appropriateness, effectiveness, equity, feasibility, fidelity, and penetration. Forty patients were included in the cluster randomized trial. Patients in the UC group ( = 13) had a median nadir S/F ratio over the 48-hour study period of 216 (95% confidence interval [95% CI], 95-303) versus 253 (95% CI, 197-267) in the APPS group ( = 27). Patients in the UC group spent 42 hours (95% CI, 13-47) of the 48-hour study period with an S/F ratio below 315 versus 20 hours (95% CI, 6-39) for patients in the APPS group. Mixed-methods analyses uncovered several barriers relevant to the conduct of a successful definitive randomized controlled trial, including low adherence to prone positioning, large differences between physician-recommended and patient-tolerated prone durations, and diffusion of prone positioning into usual care. A definitive trial evaluating the effect of prone positioning in nonintubated patients with COVID-19 is warranted, but several barriers must be addressed to ensure that the results of such a trial are informative and readily translated into practice.