Protocol summary and statistical analysis plan for the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX).

BACKGROUND: The balance of risks and benefits of conservative v standard care oxygen strategies for patients who are invasively ventilated in the intensive care unit (ICU) is uncertain. OBJECTIVE: To describe the study protocol and statistical analysis plan for the ICU randomised trial comparing two approaches to oxygen therapy (ICU-ROX). DESIGN, SETTING AND PARTICIPANTS: Protocol for a multicentre, randomised, participant and outcome assessor-blinded, standard care-controlled, parallel-group, two-sided superiority trial to be conducted in up to 22 ICUs in Australia and New Zealand. 1000 adults who are mechanically ventilated in the ICU and expected to remain ventilated beyond the day after recruitment will be randomly assigned to conservative oxygen therapy or standard care in a 1:1 ratio. ICU-ROX began with an internal pilot phase in September 2015. It is anticipated that recruitment will be completed in 2018. MAIN OUTCOME MEASURES: The primary endpoint will be alive, ventilator-free days to Day 28. Secondary outcomes include 90- and 180-day all-cause mortality, survival time to 180 days, and quality of life and cognitive function at 180 days. All analyses will be conducted on an intentionto- treat basis. RESULTS AND CONCLUSIONS: ICU-ROX will compare the effect of conservative v standard oxygen therapy in critically ill mechanically ventilated adults who are expected to be ventilated beyond the day after recruitment on ventilatorfree days to Day 28. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12615000957594).

Intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX): results of the pilot phase.

OBJECTIVE: The objective of the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX) pilot phase, which included the first 100 patients of an overall sample of 1000, was to examine feasibility. DESIGN: Investigator-initiated, prospective, parallel-group, pilot randomised controlled trial. SETTING: Six medical-surgical intensive care units (ICUs) in Australia and New Zealand, with participants recruited from September 2015 through June 2016. PARTICIPANTS: 100 patients ≥ 18 years of age who required invasive mechanical ventilation in the ICU and were expected to be receiving it beyond the next calendar day at the time of randomisation. INTERVENTIONS: Conservative oxygen therapy or standard care. MAIN OUTCOME MEASURES: Eligibility, recruitment rate, and separation in oxygen exposure (fraction of inspired oxygen [FiO2] and oxygen saturation measured by pulse oximetry [SpO2Z]). RESULTS: 94 of 99 participants (94.9%) were confirmed by study monitors to fulfil the study eligibility criteria. 3.6 patients per site per month were enrolled (95% confidence interval [CI], 2.5-4.7). Patients allocated to conservative oxygen therapy spent significantly more time on an FiO2 of 0.21 in the ICU; median, 31.5 hours (interquartile range [IQR], 7-63.5) for conservative oxygen therapy patients v 0 hours for standard oxygen therapy patients (IQR, 0-10; midpoint difference, 21.5 hours; 95% CI, 9-34; P < 0.0001). Patients allocated to conservative oxygen therapy spent less time in the ICU with an SpO2Z of ≥ 97% than patients allocated to standard oxygen therapy; median, 18.5 hours (IQR, 5-46) for conservative oxygen therapy patients v 32 hours for standard oxygen therapy (IQR, 17-80; midpoint difference, 13.5 hours; 95% CI, 2-25; P = 0.02). CONCLUSIONS: Our findings confirm the feasibility of completing the ICU-ROX trial without the need for substantive changes to the study protocol for the remaining 900 trial participants. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12615000957594).