Using an embedded implementation framework in a pilot trial of prone positioning for non-intubated hypoxic adults with COVID-19

STEPHANIE PARKS TAYLOR, MD MS
Atrium Health

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. As a Learning Health System, Atrium Health desired rapid, rigorous knowledge gain to determine whether an awake-prone positioning strategy should be implemented for hypoxic patients with COVID-19. However, because the awake prone strategy is a complex medical intervention, there are multiple implementation nuances such as adoption, feasibility, and acceptability that may affect successful conduct of a definitive RCT. We designed a pilot study with embedded implementation evaluation to rapidly inform a potential pragmatic RCT. The aim of the APPS pilot trial was to assess feasibility and contextual factors for a large RCT comparing the clinical effectiveness of awake-prone positioning versus usual care for hypoxic adults with COVID-19.

We conducted a cluster randomized pilot trial at a quaternary care teaching hospital. Five inpatient medical teams were randomly allocated to two treatment arms: 1) usual care (UC) alone; or 2) the Awake Prone Positioning Strategy plus usual care. 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 included 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.

40 patients were included in the cluster randomized trial. For the effectiveness estimate, patients in the Usual Care group spent median 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 Awake-Prone Positioning Strategy group. Six patients and 7 clinicians participated in interviews. Mixed methods analyses uncovered several barriers relevant to the conduct of a successful definitive RCT, including low patient adherence to prone positioning, large differences between physician-recommended and patient-tolerated prone durations, and physician-reported low acceptability of withholding prone positioning with considerable diffusion of prone positioning into usual care.

Using a novel pilot study design with embedded implementation evaluation, we were able to rapidly identify several barriers that must be addressed to ensure that results of a trial evaluating an awake prone positioning strategy are informative and readily translated into practice.