Acute respiratory distress syndrome (ARDS) Respiratory
Conditions
Interventions
In GUARDS, Usual Care + Dexamethasone will be compared to Usual Care. An online tool will be used to randomise patients. On days 1-5, 20mg/day of intravenous (iv) dexamethasone will be administered to
Sponsors
University of Edinburgh
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Aged 16 years or older 3. Admitted to intensive care unit or high dependency unit (ICU) 4. Receiving respiratory support via invasive mechanical ventilation or non-invasive ventilatory support (non-invasive ventilatory support includes mask or helmet) or high flow nasal cannula (HFNC) >30L/min 5. Within 72 hours of diagnosis of ARDS with moderate to severe hypoxaemia defined as 6. Known acute clinical insult or new or worsening respiratory dysfunction (Note: this includes new deterioration at any time-point during the ICU stay), and 6.1. Opacities on chest imaging not fully explained by effusions, lobar/lung collapse/atelectasis, or nodules, and 6.2. Respiratory failure not fully explained by cardiac failure or fluid overload, and 6.3. Assessment of hypoxaemia done with either PaO2/FiO2 ratio <26.7 kPa from arterial blood gases, or SpO2/FiO2 <235 with SaO2<97%
Exclusion criteria
Exclusion criteria: 1. ARDS due to microbiologically confirmed SARS-Co-V2 infection (COVID-19 ARDS) 2. Major upper gastrointestinal bleeding during current hospital admission, defined as requiring endoscopy and transfusion for two or more units of packed red blood cells. This exclusion criterion will exclude patients with contraindications to glucocorticoids on safety grounds. 3. High-dose glucocorticoids are required for a separate proven clinical indication at the time of randomisation as withholding treatments that have been deemed clinically effective, would be unethical. Note: Low-dose glucocorticoid treatments for clinical indications (defined as maximum daily dose of 200mg hydrocortisone or equivalent other steroids) is not an exclusion criterion. 4. Known hypersensitivity to dexamethasone 5. Infections that are not being effectively treated as determined by the treating medical team. Note: Once infections are considered as effectively treated by the treating medical team, they are eligible for the trial. 6. Planned intensive care treatment withdrawal within next 24 hours as determined by the treating medical team 7. Patients who are known to be pregnant 8. Previous enrolment in the GuARDS trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All-cause mortality measured using medical records at 60 days from randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Our proposed secondary outcomes (endpoints) are from the CoVENT core outcome set (COS) for ventilation trials and are measured using medical records as and when they occur: 1. First successful extubation, defined as the time from randomization until the first successful extubation or the patient’s death occurs, measured using a record of the date/time of all periods of ventilation up to day 60. Successful extubation is being free from all tubes, endotracheal tube, and tracheostomy with success being defined as remaining free from tubes at 48 hours. If discharged from the hospital before the 48-hour success period, successful extubation is assumed. 2. Duration of mechanical ventilation - Unassisted breathing, defined as no inspiratory support (includes time receiving invasive mechanical ventilation and non-invasive ventilation) or extracorporeal lung support. Success is defined as remaining to breathe unassisted at 48 hours. Defined as the time from randomization until the first successful unassisted breathing or the patient’s death occurs. Death prior to the end of mechanical ventilation or within the 48-hour period after the end of mechanical ventilation is considered censored. 3. Reintubation - All reintubation events with date/time to report the total number of reintubations after planned extubation in each group and the average number of reintubation events/participants in each group. The COS recommends reintubation rates at 60 days. To capture the risk of delayed reintubation we will collect this outcome for up to 180 days from randomization, censored at hospital discharge. 4. Duration of ICU and hospital stay at the time from randomisation until participant first leaves the relevant facility or death 5. Health-related quality of life (HRQoL) measured using the EQ-5D (www.euroqol.org) and is participant reported at 60 and 180 days post-randomisation 6. Mortality - will record the event date/time of the event, as well as the date/time of randomization to enable | — |
Countries
England, Northern Ireland, United Kingdom
Outcome results
None listed