Abstract
IMPORTANCE: Awake prone positioning (APP) has shown inconstant associations with improved clinical outcomes in nonintubated patients with COVID-19 developing severe pneumonia. OBJECTIVE: To evaluate the effects of APP on the need for intubation or incidence of death among patients with COVID-19-related hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted at 20 hospitals in France and 1 hospital in Mexico between July 2020 and August 2021. The study included patients from wards and intensive care units. Adult patients (18 years or older) who were not intubated and required at least 3 L/min of oxygen flow due to COVID-19 infection were included and randomly assigned in a 1:1 ratio to either APP or standard care. Intention-to-treat statistical analysis was performed from September to December 2024. INTERVENTION: Patients randomly assigned to the APP group were offered the intervention lasting at least 6 hours a day. Patients randomly assigned to standard care had no positioning constraint, including no contraindication to spontaneous APP. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite criterion of intubation and/or death in the first 28 days of randomization. Prespecified secondary outcomes at 28 days of enrollment were days alive outside the intensive care unit (ICU), days alive outside the hospital, proportion of patients admitted to ICU (for patients not in ICU at baseline), and days alive and free from mechanical ventilation. A bayesian approach was used to provide insights into the complete distribution of the effect estimates. RESULTS: A total of 445 patients were included in the final analysis (mean [SD] age, 60 [11] years; 329 males [74%]; median [IQR] SpO2 to FIO2 [peripheral oxygen saturation to fraction of inspired oxygen] ratio, 150 [114-194] and 155 [109-221] in the standard care and APP groups, respectively). With a noninformative prior distribution, the posterior probability that APP decreased intubation and/or death compared with standard care was 93.8% (mean odds ratio [OR], 0.74; 95% credible interval [CrI], 0.48-1.09). For secondary outcomes, between the APP and standard care groups, the mean difference in the number of days alive and free from mechanical ventilation was 0.33 (95% CrI, -1.37 to 2.03) days; in the number of days alive outside the ICU was 1.28 (95% CrI, -0.78 to 3.34) days; and in the number of days alive outside the hospital was 1.55 (95% CrI, -0.22 to 3.32) days. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of nonintubated patients with COVID-19 and hypoxemic respiratory failure, daily APP of 6 hours showed a high probability of reduced endotracheal intubation and/or death over a wide range of prior distributions. These results support APP's use in patients with hypoxemic pneumonia due to COVID-19 infection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04366856.