Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care (UK-ROX).

RESEARCH QUESTION: In non-elective invasively ventilated adults in an ICU [Population], is conservative oxygen therapy [Intervention] superior to usual oxygen therapy [Comparator] in terms of all-cause mortality at 90 days (clinical effectiveness) and incremental costs, quality-adjusted life years (QALYs) and net monetary benefit at 90 days (cost-effectiveness) [Outcome]? BACKGROUND: In the UK, around 184,000 people are admitted to an adult ICU each year. Over 30% (55,000) of these receive mechanical ventilation (MV) with supplemental oxygen, supporting them in the most critical part of their illness. This makes oxygen one of the commonest drugs given to patients in ICU. Despite this, there is insufficient evidence to guide clinicians in the use of oxygen in order to minimise the potential harm caused by too little or too much oxygen. AIMS AND OBJECTIVES: To evaluate clinical and cost effectiveness of conservative oxygen therapy on: 90 day all-cause mortality (primary clinical effectiveness outcome); incremental costs, quality-adjusted life years and net monetary benefit at 90 days (primary cost-effectiveness outcome); ICU and hospital mortality (censored at 90 days); Mortality at 60 days and one year; duration of ICU and acute hospital stay (censored at 90 days); and health-related quality of life at 90 days. DESIGN: A multi-centre, open, data-enabled randomised clinical trial (RCT) with internal pilot phase and integrated economic evaluation. SETTING: 100 NHS critical care units participating in the Case Mix Programme (CMP) national clinical audit. TARGET POPULATION: Non-elective adult (18 years and over) admissions to ICUs in the UK who are receiving invasive MV, enrolled within 12 hours of fulfilling the eligibility criteria. INTERVENTION: Conservative oxygen therapy [an arterial oxygen saturation (SpO2) target of 90 (±2)%]. For patients receiving oxygen, the lowest concentration of oxygen possible should be administered to maintain the patient’s SpO2 at 90 (±2)%. Alarms should be set to prevent an SpO2 lower than 88% and higher than 92%. COMPARATOR: Usual oxygen therapy is defined as local practice, as determined by the treating clinician. An upper SpO2 alarm must not be used. SAMPLE SIZE: 16,500 patients will achieve 90% power to detect an absolute risk reduction of 2.5% in 90 day all-cause mortality from 37% to 34.5%, allowing for 6% refusal of consent/withdrawal/loss to follow-up. [14,000 will require no additional primary data collection other than safety reporting]. TIMELINES FOR DELIVERY: The duration of this project will be 40 months. DISSEMINATION: Outputs will include meeting and conference presentations (international and national) of progress and results; publication of (1) protocol, (2) statistical analysis plan, and (3) primary results, including economic evaluation; and incorporation into guidelines. These will be targeted at relevant stakeholders in formats suitable for the target audience to ensure impact is maximised. IMPACT: UK-ROX will have a large impact on the clinical management of critically ill patients. If using a more conservative oxygen strategy is found to be clinically and cost-effective, the implementation of these outputs into clinical guidelines will reduce current variation in practice, reducing exposure to therapies and improving outcomes for a group of patients with high mortality. Data from this study will be combined with a global study of SpO2 targets in invasively ventilated patients admitted to ICUs.