Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE)

Abstract

Objectives: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19.

Design: Multicentre pragmatic randomised clinical trial.

Setting: 15 hospitals in Canada and the United States from May 2020 until May 2021.

Participants: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis.

Intervention: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position).

Main outcome measures: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen.

Results: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care.

Conclusion: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning.

Study registration: ClinicalTrials.gov NCT04383613.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: the study was funded by St Michael’s Hospital Innovation Fund, the Sinai Health Research Fund, and Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation Fund; JZ has received payments for medicolegal opinions regarding the safety and effectiveness of drugs outside the submitted work; AV is provincial clinical lead for quality improvement in general internal medicine at Ontario Health and an AMS healthcare fellow in compassion and artificial intelligence and has received funding for covid related research from CIHR, Canadian Frailty Network, St Michael's Hospital, Sinai Health System, and St Michael's Hospital Foundation; MF is a consultant for a start-up company (ProofDx) that has developed a point-of-care diagnostic test for covid-19 using CRISPR; FR has received an award from the Mak Pak Chiu and Mak-Soo Lai Hing chair in general internal medicine, University of Toronto, outside the submitted work and is an employee of Ontario Health; no other relationships or activities that could appear to have influenced the submitted work.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Fig 1

Enrolment and randomisation of participants. Among patients who withdrew owing to lack of consent, this occurred because trial allowed for deferred consent. Among patients who withdrew because they were ineligible, that was because one patient was on room air at time of randomisation and one patient was on >50% fraction of inspired oxygen (FiO2) at time of randomisation. Data for four patients who withdrew in prone arm were analysed up until withdrawal. Data from three patients who did not consent or were ineligible were not analysed. ICU=intensive care unit

Fig 2

Change in ratio of oxygen saturation to fraction of inspired oxygen (S/F ratio) over time. Creating this curve was a two step process. (1) Hourly linear interpolation of each patient's measurements. Median number of measurements per person within first 72 hours was 9 (interquartile range 6-12), and median time between first and last reading (within first 72 hours) was 55 (45- 65) hours. No extrapolation was used; patients with only one measurement were excluded. (2) Calculation of mean and confidence interval at each hour for each cohort