Awake prone positioning of hypoxaemic patients with COVID-19: protocol for a randomised controlled open-label superiority meta-trial

Abstract

Introduction: Prone positioning (PP) is an effective first-line intervention to treat patients with moderate to severe acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, as it improves gas exchanges and reduces mortality. The use of PP in awake spontaneous breathing patients with ARDS secondary to COVID-19 was reported to improve oxygenation in few retrospective trials with small sample size. High-level evidence of awake PP for hypoxaemic patients with COVID-19 patients is still lacking.

Methods and analysis: The protocol of this meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled open label superiority trials. This design is particularly adapted to a rapid scientific response in the pandemic setting. It will take place in multiple sites, among others in USA, Canada, Ireland, France and Spain. Patients will be followed up for 28 days. Patients will be randomised to receive whether awake PP and nasal high flow therapy or standard medical treatment and nasal high flow therapy. Primary outcome is defined as the occurrence rate of tracheal intubation or death up to day 28. An interim analysis plan has been set up on aggregated data from the participating research groups.

Ethics and dissemination: Ethics approvals were obtained in all participating countries. Results of the meta-trial will be submitted for publication in a peer-reviewed journal. Each randomised controlled trial was registered individually, as follows: NCT04325906, NCT04347941, NCT04358939, NCT04395144 and NCT04391140.

Keywords: COVID-19; adult intensive & critical care; international health services; respiratory infections; statistics & research methods.

Conflict of interest statement

Competing interests: IP has been a speaker for Fisher & Pakyel Healthcare within the last 3 years. All compensation was paid to the charitable foundation at the hospital where he works, and he did not personally receive any compensation. JL discloses research support from Fisher & Paykel Healthcare for another research project. SE received unrestricted research grants, travel fee reimbursements and speaker fees from Fisher & Paykel Healthcare, consulting fees from La Diffusion Technique Française, consulting fees and unrestricted research grants from Aerogen Ltd and an unrestricted research grant from Hamiton medical. OR provides consultancy to Hamilton Medical but he did not receive any personal fee. All compensation were received by the Institute of Research of his Institution. He received speaker fees by Air Liquide. J-PF reports grants from the French Ministry of Health; grants, personal fees and non-financial support from Fisher & Paykel Heathcare; personal fees and non-financial support from SOS oxygene, outside the submitted work.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Efficacy and futility stopping boundaries: analyses are planned every 200 patients randomised in the various trials. The interim analyses define rules for stopping the trials early for the statistical reasons of established efficacy or futility on the primary outcome. Bounds were determined using a Kim-DeMets spending function with an aggressive Pocock superiority and a conservative O’Brien Fleming bound for futility.