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Multicenter Study
. 2025 Aug 5;334(5):398-408.
doi: 10.1001/jama.2025.9663.

Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial

Daniel S Martin  1   2 , Doug W Gould  3 , Tasnin Shahid  3 , James C Doidge  3 , Alex Cowden  3 , Zia Sadique  4 , Julie Camsooksai  3 , Walton N Charles  3 , Miriam Davey  5 , Amelia Francis-Johnson  3 , Roger M Garrett  6 , Michael P W Grocott  7 , Joanne Jones  5 , Lamprini Lampro  3 , Diane M Mackle  8 , B Ronan O'Driscoll  9 , Alvin Richards-Belle  3 , Anthony J Rostron  10 , Tamás Szakmány  11 , Alex Warren  3   12   13 , Paul J Young  14   15   16 , Kathryn M Rowan  3 , David A Harrison  3 , Paul R Mouncey  3 ; UK-ROX Investigators
Collaborators, Affiliations
Multicenter Study

Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial

Daniel S Martin et al. JAMA. .

Abstract

Importance: Supplemental oxygen is frequently given to patients in intensive care units (ICUs); however, there is insufficient evidence to guide its therapeutic use and to minimize the potential harm caused by administering too little or too much.

Objective: To determine whether reducing exposure to supplemental oxygen through a strategy of conservative oxygen therapy by using a peripheral oxygen saturation (Spo2) target of 90% (range, 88%-92%) reduces mortality at 90 days in mechanically ventilated adult patients receiving supplemental oxygen in the ICU.

Design, setting, and participants: Multicenter, pragmatic, randomized clinical trial conducted in 97 ICUs in the UK including 16 500 mechanically ventilated patients receiving supplemental oxygen. Participants were enrolled between May 2021 and November 2024. Follow-up was completed in February 2025.

Interventions: Participants randomized to conservative oxygen therapy (n = 8258) received the lowest fraction of inspired oxygen possible to maintain their Spo2 at 90%. Participants randomized to usual oxygen therapy (n = 8242) received oxygen therapy at the discretion of the treating clinician.

Main outcomes and measures: The primary outcome was all-cause mortality at 90 days. Secondary outcomes included duration of ICU and acute hospital stay among survivors, days alive and free from organ support at 30 days, and mortality at other time points.

Results: Of 16 500 randomized patients, primary outcome data were available for 16 394 (8211 in the conservative and 8183 in the usual oxygen therapy group). Randomized groups were similar (median age, 60 [IQR, 48-71] years and 38.2% females in both groups [n = 5652]). Exposure to supplemental oxygen was 29% lower for participants in the conservative oxygen therapy group compared with the usual oxygen therapy group. By 90 days, 2908 participants (35.4%) in the conservative oxygen therapy group had died compared with 2858 (34.9%) in the usual oxygen therapy group. After adjustment for prespecified baseline variables, the risk difference was 0.7 percentage points (95% CI, -0.7 to 2.0; P = .28). There were no significant differences in durations in ICU or hospital stay, days alive and free from organ support at 30 days, or mortality at other time points.

Conclusions and relevance: In adult patients receiving mechanical ventilation and supplemental oxygen in the ICU, minimizing oxygen exposure through conservative oxygen therapy did not significantly reduce all-cause mortality at 90 days.

Trial registration: isrctn.org Identifier: ISRCTN13384956.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Martin reported being editor in chief of the Journal of the Intensive Care Society and receiving grants 135577 and 129318 from the National Institute for Health and Care Research (NIHR). Dr Doidge reported receiving grants the Medical Research Council UK during the conduct of the study. Dr Charles reported having conducted this work during an NIHR-funded Pre-doctoral Fellowship in Epidemiology (NIHR302788). Dr Grocott reported being funded in part by the NIHR Southampton Biomedical Research Centre and the NIHR Senior Investigator Scheme; serving on the medical advisory board of Becton Dickinson and Edwards Lifescience Ltd, from which he has received honoraria and unrestricted study funding outside the submitted work. Dr Mackle reported receiving grants from Health Research Council of New Zealand Medical Research Institute, independent research organization funding from the New Zealand Health Research Council (HRC) during the conduct of the study and grants from the HRC of New Zealand Medical Research Institute, and independent research organization funding from HRC outside the submitted work. Dr Szakmány reported receiving grants from NIHR and Healthcare Infection Society and speaker fees from Biotest AG and ThermoFisher Ltd and serving as the editor in chief of Critical Care Explorations and as a trustee of the Intensive Care National Audit and Research Centre as an unpaid volunteer. Dr Warren reported being supported by an NIHR research doctoral fellowship (NIHR303715) during the conduct of the study. Dr Young reported receiving a clinical practitioner research fellowship from HRC of New Zealand. Dr Rowan reported being the director of the NIHR Health and Social Care Delivery Research Programme. Dr Harrison reported being a member of the general funding committee for the NIHR Health Technology Assessment Programme. No other disclosures were reported.

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