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

Abstract

Rationale: 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. Objectives: 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. 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 (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. Results: Forty patients were included in the cluster randomized trial. Patients in the UC group (n = 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 (n = 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. Conclusions: 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.

Keywords: COVID-19; hypoxia; implementation science; prone positioning.

Figure 1.

Flow diagram of patients with COVID-19 acute respiratory failure enrolled into the APPS pilot trial. AMA = against medical advice; APPS = Awake Prone Positioning Strategy; COVID-19 = coronavirus disease.

Figure 2.

Separation of lowest S/F ratio and trends in median S/F ratio within 48 hours from baseline for patients with coronavirus disease (COVID-19) acute respiratory failure enrolled into the APPS pilot trial. Box and whisker plots depict the lowest S/F ratio for (A) patients randomly assigned to UC and APPS and (B) patients who did not prone and did prone. Median and IQR and mean and SD estimates along with 95% CIs are shown below the plot for each group. Outlier data points are presented with a circle for any estimates located at least 1.5 times the IQR below the first quartile or above the third quartile. The group median S/F ratio is shown plotted longitudinally at 6-hour intervals for (C) patients randomly assigned to UC and APPS and (D) patients who did not prone and did prone. APPS = Awake Prone Positioning Strategy; CI = confidence interval; IQR = interquartile range; SD = standard deviation; S/F = oxygen saturation to fraction of inspired oxygen; UC = usual care.