Glucocorticoids in Adults With Acute Respiratory Distress Syndrome: Randomised Clinical Trial (GuARDS Trial)

Research question: What is the clinical and cost effectiveness of dexamethasone given early (within 72 hours of diagnosis) in acute respiratory distress syndrome (ARDS)? Design: Multi-centre, parallel group, allocation concealed, open label, pragmatic, group sequential design randomised controlled trial, with internal pilot Setting: Approximately 60 UK intensive care units (ICUs) Target population: Adult ICU patients with moderate-to-severe ARDS Inclusion criteria: --Aged >=16 years --Moderate or severe ARDS, as defined by the Berlin Consensus criteria for ARDS. Briefly this includes a)ARDS within 1 week of a known clinical insult and b)bilateral opacities on chest imaging and c)respiratory failure not fully explained by cardiac failure or fluid overload and d)Hypoxaemia defined as PaO2/FiO2 ratio <26.6 kPa with PEEP =5 cm water. -Within 72 hours of meeting ARDS criteria Exclusion criteria: -ARDS due to confirmed SARS-Co-V2 infection (COVID-19 ARDS) -Major upper gastrointestinal bleeding during current hospital admission, defined as requiring endoscopy and transfusion for two or more units of packed red blood cells -Glucocorticoids are required for a proven clinical indication (note: stress dose steroids required for septic shock will not be excluded) -Hypersensitivity to dexamethasone -Treatment withdrawal imminent within 24 hours -Previous enrolment in the trial Health technologies being assessed: Intravenous dexamethasone 20mg OD day 1 to day 5, reduced to 10 mg OD day 6 to day 10. Measurement of costs and outcomes Primary: All-cause mortality 60 days post-randomisation Secondary: -In hospital: Successful extubation; Duration of mechanical ventilation; ICU, and hospital length of stay; Health-related quality of life (HRQOL) and adverse events. -At 90-days: HRQoL; Mortality -At 180-days: Reintubation; Mortality; HRQoL; Health service use Health economic evaluation: Cost-effectiveness from NHS and personal social services perspective as per NICE reference case specifications. Follow up: Up to 180 days post-randomisation. Sample size: 854 per group (1708 in total). Timeline:Start date is 01-03-2023. Prior to start date and in conjunction with PPI, we will draft the protocol, and site training materials. We expect a lead time of 6 months to secure ethical and regulatory approvals. We plan to set up 5-10 sites/month, and recruit the first patient in month 7. We estimate duration of recruitment to achieve a sample size of 1708 will be 42 months (at 0.8 participants/site/month). We will undertake an internal pilot for the first 9 months of recruitment, to set-up all 60 sites and recruit 268 patients. Participants will be followed-up for 6 months and further 6-months for close-down, data-cleaning, analysis and reporting. The total study duration is 60 months. Expertise: Our multi-professional team includes clinical trialists, leaders in critical care, pharmacists, methodologists, statistician, health economist, and family representatives, to optimise all aspects of trial delivery. Anticipated impact and dissemination: The results of this definitive trial will establish best clinical care where there is uncertainty, and will determine best value for services. Dissemination will take multiple routes including publication in international, high impact factor, journals, presentation at relevant national and international conferences, and communication with involved participant and family networks including social media and lay press.