Covid19, Hypoxia
Conditions
Keywords
Randomised clinical trial, COVID-19, Hypoxia, Corticosteroids
Brief summary
We aim to assess the benefits and harms of higher (12 mg) vs lower doses (6 mg) of dexamethasone on patient-centered outcomes in patients with COVID-19 and severe hypoxia.
Detailed description
Background: Preliminary results from the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial have reported a reduction in 28-day mortality with low-dose dexamethasone (6 mg) once daily versus no intervention in hospitalised patients with COVID-19; an effect that may have been more pronounced in patients with increasing hypoxia. Yet, higher doses of dexamethasone may be beneficial in patients with non-COVID-19 acute respiratory distress syndrome. At present, it is unclear what dose of dexamethasone is most beneficial in patients with COVID-19 and severe hypoxia, and clinical equipoise exists. Objective: We aim to assess the effects of higher (12 mg) vs lower doses (6 mg) of intravenous dexamethasone on the number of days alive without life-support in adult patients with COVID-19 and severe hypoxia. Design: International, parallel-group, centrally randomised, stratified, blinded, clinical trial. Population: Adult patients with documented COVID-19 receiving at least 10 L/min of oxygen independent of delivery system OR mechanical ventilation. Experimental intervention: Dexamethasone 12 mg once daily for up to 10 days in addition to standard care. Control intervention: Dexamethasone 6 mg once daily for up to 10 days in addition to standard care. Outcomes: The primary outcome is days alive without life support (i.e. mechanical ventilation, circulatory support, or renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions (i.e. anaphylactic reaction to hydrocortisone, new episode of septic shock, invasive fungal infection or clinically important gastrointestinal bleeding) at day 28; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, 90 and 180; and health-related quality of life at day 180. Sample size: A total of 1000 participants will be randomised in order to detect a 15% relative reduction in 28-day mortality combined with a 10% reduction in time on life support among the survivors with a power of 85%.
Interventions
DRUGDexamethasone
ATC code: H02AB02
Sponsors
Copenhagen Trial Unit, Center for Clinical Intervention Research
Centre for Research in Intensive Care (CRIC)
Aarhus University Hospital
Aalborg University Hospital
Rigshospitalet, Denmark
The George Institute for Global Health, Australia
Scandinavian Critical Care Trials Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All of the following must be fulfilled * Aged 18 years or above AND * Confirmed SARS-CoV-2 (COVID-19) requiring hospitalisation AND * Use of one of the following: * Invasive mechanical ventilation OR * Non-invasive ventilation or continuous use of continuous positive airway pressure (CPAP) for hypoxia OR * Oxygen supplementation with an oxygen flow of at least 10 L/min independent of delivery system
Exclusion criteria
We will exclude patients who fulfil any of the following criteria: * Use of systemic corticosteroids for other indications than COVID-19 in doses higher than 6 mg dexamethasone equivalents * Use of systemic corticosteroids for COVID-19 for 5 days consecutive days or more * Invasive fungal infection * Active tuberculosis * Fertile woman (\<60 years of age) with positive urine human gonadotropin (hCG) or plasma-hCG * Known hypersensitivity to dexamethasone * Previously randomised into the COVID STEROID 2 trial * Informed consent not obtainable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days alive without life support at day 28 | Day 28 after randomisation | Days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) from randomisation to day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality at day 28 | Day 28 after randomisation | Death from all causes |
| All-cause mortality at day 90 | Day 90 after randomisation | Death from all causes |
| Days alive without life support at day 90 | Day 90 after randomisation | Days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) from randomisation to day 90 |
| Number of participants with one or more serious adverse reactions | Day 28 after randomisation | Serious adverse reactions defined as new episodes of septic shock, invasive fungal infection, clinically important gastrointestinal bleeding or anaphylactic reaction |
| All-cause mortality at day 180 | Day 180 after randomisation | Death from all causes |
| Health-related quality of life at day 180 | Day 180 after randomisation | Assessed by EQ-5D-5L |
| Days alive and out of hospital at day 90 | Day 90 after randomisation | Number of days alive and out of hospital not limited to the index admission |
Countries
Denmark, India, Sweden, Switzerland
Outcome results
None listed