Ann Am Thorac Soc. 2020 Dec 23. doi: 10.1513/AnnalsATS.202009-1164OC. Online ahead of print.
RATIONALE: Prone positioning is an appealing therapeutic strategy for non-intubated hypoxic patients with COVID-19 but its effectiveness remains to be established in randomized controlled trials.
OBJECTIVE: To identify contextual factors relevant to the conduct of a definitive clinical trial evaluating a prone positioning strategy for non-intubated hypoxic patients with COVID-19.
METHODS: 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: 1) usual care (UC) consisting of current, standard management of hypoxia and COVID-19; or 2) the Awake Prone Positioning Strategy plus usual care (APPS). Included patients had positive SARS-CoV-2 testing or suspected COVID-19 pneumonia and oxygen saturation less than 93% or new oxygen requirement of 3 liters 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 ratio (S/F) and time spent with S/F ratio less than 315. Concurrently, we conducted an embedded implementation evaluation using semi-structured 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.
RESULTS: 40 patients were included in the cluster randomized trial. Patients in the Usual Care group (n=13) had a median nadir S/F ratio over the 48-hour study period of 216 [95%CI=95-303] versus 253 [95%CI=197-267] in the APPS group (n=27). Patients in the Usual Care group spent 42 hours [95%CI=13-47] of the 48-hour study period below S/F ratio < 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 RCT, including low adherence to prone positioning, large differences between physician-recommended and patient-tolerated prone durations, and diffusion of prone positioning into usual care.
CONCLUSIONS: A definitive trial evaluating the effect of prone positioning in non-intubated patients with COVID-19 is warranted, but several barriers must be addressed to ensure that results of such a trial are informative and readily translated into practice.