Airway Pressure Release Ventilation (APRV) vs conventional ventilation for patients with moderate to severe acute hypoxemic respiratory failure (RELEASE)

Research question What is the clinical and cost-effectiveness of airway pressure release ventilation (APRV) for adults requiring invasive mechanical ventilation (IMV) for moderate-severe acute hypoxaemic respiratory failure (AHRF)? Background Many patients with AHRF require IMV. IMV is associated with morbidity and mortality which may in part be attributable to the way IMV is delivered. Significant NHS costs are incurred (average £1864/ICU day, average IMV duration 6 days) with total costs increasing with IMV duration. IMV optimisation could reduce lung damage thereby reducing IMV duration, mortality, and costs. AHRF survivors experience reduced quality of life, with substantial costs to the NHS and to society. APRV is an innovative ventilatory strategy available on all ICU ventilators at no additional cost to the NHS. APRV may minimise ventilator induced lung injury by maintaining lung volume, preventing excessive lung stretch and collapse. APRV moves gas into the lungs over a longer inspiration time, resulting in greater and more uniform lung inflation improving gas exchange with less risk of injury. If APRV reduces the time spent receiving IMV this may shorten time to return to pre-ICU quality of life. Aims and objectives Our overall aim is to investigate the clinical and cost effectiveness of early APRV compared to conventional IMV in moderate-severe AHRF. Our primary objective is to determine the potential for APRV to reduce IMV duration following randomisation compared to usual care. Secondary objectives are to determine the effect on all-cause mortality at 60 days, 6 months, and 1 year; time to first successful extubation; reintubation rates; ICU and hospital length of stay; serious adverse events to ICU discharge; and health related quality of life (EQ-5D-5L) at 2 and 6 months. We will perform an embedded economic evaluation to estimate cost-effectiveness. Methods Randomised, allocation concealed, controlled, open label, pragmatic, clinical and cost effectiveness trial (with internal pilot) comparing APRV to usual care. We will recruit participants from at least 40 ICUs across the UK, including areas with high disease prevalence to maximise the generalisability of findings. Inclusion criteria: age =18 years; receiving IMV; PaO2/FiO2 48hrs. We have selected exclusion criteria to ensure early APRV use and exclusion of patients unlikely to benefit due to underlying conditions or increased risk of complications. We will conduct a within-trial cost-utility analysis from an NHS hospital care perspective. Timelines We estimate 7 months for regulatory approvals and 8 months for internal pilot. With staggered site set-up, total recruitment duration including the internal pilot is 32 months. We estimate 13 months for follow-up, analysis and report writing. Total duration: 52 months. Anticipated impact and dissemination This definitive trial will establish best clinical care where there is uncertainty and will determine best value for the NHS. We will use a multi-modal dissemination strategy: open access publication in high impact factor journals; presentation at relevant national/international scientific conferences; and communication with participant and family networks including social media and lay press with a lay results summary to participants.