Protocol for a feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients.

Introduction: Oxygen is the most commonly administered drug to mechanically ventilated critically ill adults, yet little is known about the optimum oxygen saturation (SpO ₂ ) target for these patients; the current standard of care is an SpO ₂ of 96% or above. Small pilot studies have demonstrated that permissive hypoxaemia (aiming for a lower SpO ₂ than normal by using a lower fractional inspired oxygen concentration (FIO ₂ )) can be achieved in the critically ill and appears to be safe. This approach has not been evaluated in a National Health Service setting. It is possible that permissive hypoxaemia may be beneficial to critically ill patients thus it requires robust evaluation.
Methods and Analysis: Targeted OXygen therapY in Critical illness (TOXYC) is a feasibility randomised controlled trial (RCT) to evaluate whether recruiting patients to a study of permissive hypoxaemia is possible in the UK. It will also investigate biological mechanisms that may underlie the links between oxygenation and patient outcomes. Mechanically ventilated patients with respiratory failure will be recruited from critical care units at two sites and randomised (1:1 ratio) to an SpO ₂ target of either 88%-92% or ≥96% while intubated with an endotracheal tube. Clinical teams can adjust FIO ₂ and ventilator settings as they wish to achieve these targets. Clinical information will be collected before, during and after the intervention and blood samples taken to measure markers of systemic oxidative stress. The primary outcome of this study is feasibility, which will be assessed by recruitment rate, protocol adherence and withdrawal rates. Secondary outcomes will include a comparison of standard critical care outcome measures between the two intervention groups, and the measurement of biomarkers of systemic oxidative stress. The results will be used to calculate a sample size, likely number of sites and overall length of time required for a subsequent large multicentre RCT.
Ethics and Dissemination: This study was approved by the London - Harrow Research Ethics Committee on 2 November 2017 (REC Reference 17/LO/1334) and received HRA approval on 13 November 2017. Results from this study will be disseminated in peer-reviewed journals, at medical and scientific meetings, in the NIHR Journals Library and patient information websites.
Trial Registration Number: NCT03287466; Pre-results.
Competing Interests: Competing interests: DSM, MM and MPWG are directors of a company developing an oxygen delivery device (Oxygen Control Ltd). DSM has received honoraria and consultancy fees from Siemens Healthcare, Masimo, Deltex and Edwards Lifesciences. MPWG is the National Specialty Lead for Anaesthesia, Perioperative Medicine and Pain within the UK National Institute of Heath Research Clinical Research Network, an elected council member of the Royal College of Anaesthetists and serves on the board of the Evidence Based Perioperative Medicine (EBPOM) social enterprise and the medical advisory board of Sphere Medical Ltd. MPWG has received honoraria for speaking and/or travel expenses from Edwards Lifesciences, Fresenius-Kabi, BOC Medical (Linde Group), Ely-Lilly Critical Care, and Cortex GmBH. MPWG is executive chair of the Xtreme-Everest Oxygen Research Consortium and joint Editor-in-Chief of the journal Perioperative Medicine. MM is a consultant for Baxter, Edwards Lifesciences and Deltex; his University Chair is supported by Smiths Medical; Elected Council Member Royal College of Anaesthetsists; Editorial Board BJA and Critical Care; Founding Editor-in-Chief Perioperative Medicine.
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