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Randomized Controlled Trial
. 2022 Jun 7;327(21):2104-2113.
doi: 10.1001/jama.2022.7993.

Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial

Waleed Alhazzani  1   2   3   4 , Ken Kuljit S Parhar  5   6   7 , Jason Weatherald  6   7   8   9 , Zainab Al Duhailib  10   11 , Mohammed Alshahrani  12 , Abdulrahman Al-Fares  13 , Sarah Buabbas  14 , Sujith V Cherian  15 , Laveena Munshi  16   17 , Eddy Fan  16   17 , Fahad Al-Hameed  18   19 , Jamal Chalabi  20   21 , Amera A Rahmatullah  10 , Erick Duan  1   2   4   22 , Jennifer L Y Tsang  1   22 , Kimberley Lewis  1   4 , François Lauzier  23   24 , John Centofanti  25 , Bram Rochwerg  1   2 , Sarah Culgin  4 , Katlynne Nelson  4 , Sheryl Ann Abdukahil  26   27   28 , Kirsten M Fiest  5   29   30 , Henry T Stelfox  5   29 , Haytham Tlayjeh  26   27   28 , Maureen O Meade  1   2 , Dan Perri  1   4 , Kevin Solverson  5   8 , Daniel J Niven  5 , Rachel Lim  8 , Morten Hylander Møller  31 , Emilie Belley-Cote  1   32 , Lehana Thabane  2   4 , Hani Tamim  11   33 , Deborah J Cook  1   2   4 , Yaseen M Arabi  26   27   28 ; COVI-PRONE Trial Investigators and the Saudi Critical Care Trials Group
Collaborators, Affiliations
Randomized Controlled Trial

Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial

Waleed Alhazzani et al. JAMA. .

Abstract

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.

Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.

Design, setting, and participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.

Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195).

Main outcomes and measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events.

Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group.

Conclusions and relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit.

Trial registration: ClinicalTrials.gov Identifier: NCT04350723.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Parhar reported receiving Rapid COVID-19 grants from the Cumming School of Medicine at the University of Calgary and Alberta Innovates. Dr Weatherald reported receiving Rapid COVID-19 grants from the Cumming School of Medicine at the University of Calgary; receiving grants, personal fees, and nonfinancial support from Janssen, Actelion, and Bayer; and receiving personal fees from Acceleron and Merck. Dr Alshahrani reported receiving grants from King Abdullah International Medical Research Center. Dr Fan reported receiving personal fees from ALung Technologies, Baxter, Aerogen, Inspira, GE Healthcare, and Vasomune. Dr Belley-Cote reported receiving grants from Bayer, Bristol Myers Squibb-Pfizer Alliance, and Roche Diagnostics. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Screening, Enrollment, Randomization, and Inclusion in Analysis in the COVI-PRONE Trial
COVI-PRONE, Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19. aNo data were collected on screened patients found to be ineligible. bCentral web-based randomization stratified by hospital and by ratio of oxygen saturation as measured by pulse oximetry to fraction of inspired oxygen of greater than 150 or of 150 or less.
Figure 2.
Figure 2.. Duration of Awake Prone Positioning by Study Group
The box plots display the median duration of prone positioning. The line represents 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.
Figure 3.
Figure 3.. Kaplan-Meier Survival Curves for Endotracheal Intubation Within 30 Days of Randomization and Mortality at 60 Days
A, The log-rank test did not demonstrate a significant between-group difference (P = .19). The median time of observation was 30 days (IQR, 7-30 days) in the awake prone positioning group and 30 days (IQR, 5-30 days) in the control group. B, The log-rank test did not demonstrate a significant between-group difference (P = .72). In both groups, the median time of observation was 60 days (IQR, 60-60 days).
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