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.
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%.
Drug: Dexamethasone
ATC code: H02AB02
Other Name: Dexavit
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
Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital, Denmark.
Aalborg, Denmark
Dept. of Intensive care, Aarhus University Hospital
Aarhus, Denmark
Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark
Dept. of Neuroanaesthesiology
Copenhagen, Denmark
Dept. of Thoracic Anaesthesiology, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark
Dept of Infectious diseases, Copenhagen University Hospital, Rigshospitalet
Copenhagen, Denmark
Dept. of Intensive Care, Gentofte Hospital
Hellerup, Denmark
Dept. of Anaesthesia and Intensive Care, Herlev Hospital
Herlev, Denmark
Dept. of Anaesthesia, Regional Hospital West Jutland, Herning
Herning, Denmark
Dept. of Intensive Care, Nordsjællands Hospital - Hillerød, Denmark.
Hillerød, Denmark
Hvidovre Hospital - Dept of Infectious diseases
Hvidovre, Denmark
Hvidovre Hospital - Dept of Intensive Care
Hvidovre, Denmark
Hvidovre Hospital - Dept of Pulmonary Medicine
Hvidovre, Denmark
Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital
Kolding, Denmark
Dept. of Intensive Care, Køge University Hospital
Køge, Denmark
Dept of Intensive Care, Odense University Hospital
Odense, Denmark
Dept. of Anaesthesia and Intensive Care, Zealand University Hospital Roskilde
Roskilde, Denmark
Dept. of Anaesthesia, Slagelse Hospital
Slagelse, Denmark
Dept. of Anaesthesia and Intensive Care, Viborg Hospital
Viborg, Denmark
Jawahar Lal Nehru Medical Collega, AMU
Aligarh, India
Apollo Hospital
Chennai, India
Amrita Institute of Medical Sciences
Kochi, India
Bombay Hospital & Medical Research Centre
Mumbai, India
K. J. Somaiya Super Specialty Hospital
Mumbai, India
P. D. Hinduja National Hospital & Medical Research Centre
Mumbai, India
S L Raheja Fortis Hospital
Mumbai, India
Tata Memorial Hospital
Mumbai, India
Wockhardt hospitals
Mumbai, India
Indraprastha Apollo Hospital
New Delhi, India
Max Super Specialty Hospital, Saket
New Delhi, India
Symbiosis University Hospital and Research Centre
Pune, India
Vishwaraj Hospital
Pune, India
Rajendra Institute of Medical Sciences
Ranchi, India
Gotri General Hospital
Vadodara, India
Christian Medical College Vellore
Vellore, India
Dept. of Anaesthesia and Intensive Care, Sahlgranska Universitetssjukhuset
Göteborg, Sweden
Dept. of Infectious Diseases, Sahlgranska Universitetssjukhuset
Göteborg, Sweden
Dept. of Anaesthesia and Intensive Care, Universitetssjukhuset i Linköping
Linköping, Sweden
Dept. of Anaesthesia and Intensive Care, Skånes Universitetssjukhus (SUS) Malmö
Malmö, Sweden
Dept. of Infectious Diseases, Skånes Universitetssjukhus (SUS) Malmö
Malmö, Sweden
Dept. of Anaesthesia and Intensive Care, Vrinnevisjukhuset, Norrköping
Norrköping, Sweden
Dept. of Anaesthesia and Intensive Care, Capio St Görans Sjukhus
Stockholm, Sweden
Dept. of Anaesthesia and Intensive Care, Danderyds Sjukhuset
Stockholm, Sweden
Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Huddinge
Stockholm, Sweden
Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Solna
Stockholm, Sweden
Dept. of Cardiology, Södersjukhuset
Stockholm, Sweden
Dept. of Infectious Diseases, Danderyds Sjukhuset
Stockholm, Sweden
Dept. of Infectious Diseases, Karolinska Universitetssjukhuset, Solna
Stockholm, Sweden
Dept. of Infectious Diseases, Södersjukhuset
Stockholm, Sweden
Dept. of Internal Medicine, Danderyds Sjukhuset
Stockholm, Sweden
Dept. of Internal Medicine, Södersjukhuset
Stockholm, Sweden
Södersjukhuset
Stockholm, Sweden
Dept. of Intensive Care Medicine, Bern University Hospital (Inselspital)
Bern, Switzerland