Prolonged vs shorter awake prone positioning for COVID-19 patients with acute respiratory failure: a multicenter, randomised controlled trial

Abstract

Purpose: Awake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes.

Methods: In this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events.

Results: In total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12-14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2-8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42-0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37-0.86), and for mortality was 0.63 (0.42-0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups.

Conclusion: Prolonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF.

Trial registration: ClinicalTrials.gov NCT05677984.

Keywords: COVID-19-related acute respiratory failure; Intubation; Mortality; Prolonged awake prone positioning.

Fig. 1

Screening, enrolment, randomization, and follow-up of trial participants. BMI body-mass index, NYHA New York holstein association, CPAP Continuous positive airway pressure

Fig. 2

Duration of Awake Prone Positioning and Kaplan–Meier probabilities estimates in the intention-to-treat population. A The box plots display the median durations of prone positioning. The lines represent the median, the box edges represent the first and third quartiles, the whiskers represent the most extreme values up to 1.5 × IQR, and the dots represent the more extreme values. B Probability of endotracheal intubation^*. The log-rank test demonstrated a significant between-group difference (P = 0.0092). ^*Patients who refused intubation after randomization were included as NOT being intubated. C Probability of death. The log-rank test demonstrated a significant between-group difference (P = 0.045)