Title: Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care (UK-ROX).
Funder: Department of Health and Social Care

Abstract: Around 184,000 critically ill adults are admitted to intensive care units (ICUs) each year in the UK. Over 30% of these will require help from a breathing machine (called a ventilator), often in combination with additional oxygen. As such, oxygen is the most common therapy used to treat patients admitted to an ICU, who require help from a ventilator. Despite this, we do not know how much oxygen to give to patients in order to optimise their recovery. _x000D_ _x000D_ Doctors and nurses adjust the amount of oxygen given to a patient based on how much oxygen is in their blood, known as oxygen saturations. While we know that very low oxygen saturations are harmful, current research shows that very high saturations may also be dangerous for extremely ill patients. However, for patients being treated in an ICU and needing help from a ventilator, this has only been looked at in a few small studies and the findings have been inconclusive._x000D_ _x000D_ Our aim is to find out whether keeping oxygen saturations at lower levels (conservative oxygen therapy) is better than the higher level that is currently being used in the NHS to treat patients in ICU needing help from a ventilator. We believe that aiming for lower oxygen saturations may improve a patient’s chances of survival and long-term health. The results of this study will have a large and immediate impact on clinical practice and on outcomes for critically ill patients throughout the NHS. _x000D_ _x000D_ We plan to conduct a large-scale clinical trial involving 16,500 adults from 100 NHS ICUs. They will be randomly assigned (like a coin toss) to receive oxygen aiming to keep their saturations at either lower or higher levels. This type of study is known as a randomised clinical trial and ensures that the two groups are as similar as possible, apart from the level of oxygen they receive. All other medical care will be decided by the doctors and nurses. We will follow-up all patients at 90 days after they entered the study by linking data from the study with records in a nationally held routine dataset. We will determine the effectiveness of aiming for lower oxygen saturations by comparing the number of patients alive in each group at this time point. The data collected from the 16,500 patients enrolled into this study will also be included in a global study of 40,000 patients investigating oxygen levels in critically ill patients being treated in ICUs around the world. _x000D_ _x000D_ We have patient and public representatives as co-investigators on this study. They have been involved in the design of the study and how the study will be conducted. They will also help to oversee the conduct and management of the study._x000D_ _x000D_ Once the study is complete, the results will be published in widely read and well-regarded medical journals. The results will also be presented at various national and international conferences for intensive care doctors, nurses, other health professionals, managers and policy makers. We will also make the results available to the public and patients through our website.

Lay abstract: 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]?_x000D_ _x000D_ 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._x000D_ _x000D_ 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._x000D_ _x000D_ DESIGN: A multi-centre, open, data-enabled randomised clinical trial (RCT) with internal pilot phase and integrated economic evaluation._x000D_ _x000D_ SETTING: 100 NHS critical care units participating in the Case Mix Programme (CMP) national clinical audit._x000D_ _x000D_ 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._x000D_ _x000D_ 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%._x000D_ _x000D_ COMPARATOR: Usual oxygen therapy is defined as local practice, as determined by the treating clinician. An upper SpO2 alarm must not be used._x000D_ _x000D_ 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]._x000D_ _x000D_ TIMELINES FOR DELIVERY: The duration of this project will be 40 months._x000D_ _x000D_ 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._x000D_ _x000D_ 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.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY