Higher vs. Lower Doses of Dexamethasone for COVID-19 and Severe Hypoxia
- Registration Number
- NCT04509973
- Lead Sponsor
- Scandinavian Critical Care Trials Group
- 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%.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1000
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dexamethasone 12 mg Dexamethasone Intravenous bolus injection of dexamethasone 12 mg once daily in addition to standard care for up to 10 days. We will allow the use of betamethasone 12 mg at sites, where dexamethasone is not available. Dexamethasone 6 mg Dexamethasone Intravenous bolus injection of dexamethasone 6 mg once daily in addition to standard care for up to 10 days. We will allow the use of betamethasone 6 mg at sites, where dexamethasone is not available.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method All-cause mortality at day 28 Day 28 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
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
Health-related quality of life at day 180 Day 180 after randomisation Assessed by EQ-VAS
All-cause mortality at day 90 Day 90 after randomisation Death from all causes
All-cause mortality at day 180 Day 180 after randomisation Death from all causes
Trial Locations
- Locations (53)
Max Super Specialty Hospital, Saket
🇮🇳New Delhi, India
Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Huddinge
🇸🇪Stockholm, Sweden
Dept. of Infectious Diseases, Sahlgranska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Dept. of Infectious Diseases, Skånes Universitetssjukhus (SUS) Malmö
🇸🇪Malmö, Sweden
Dept. of Anaesthesia and Intensive Care, Universitetssjukhuset i Linköping
🇸🇪Linköping, Sweden
Dept. of Anaesthesia and Intensive Care, Danderyds Sjukhuset
🇸🇪Stockholm, Sweden
Dept. of Cardiology, Södersjukhuset
🇸🇪Stockholm, Sweden
Dept. of Infectious Diseases, Södersjukhuset
🇸🇪Stockholm, Sweden
Dept. of Internal Medicine, Danderyds Sjukhuset
🇸🇪Stockholm, Sweden
Apollo Hospital
🇮🇳Chennai, India
Dept. of Anaesthesia and Intensive Care, Vrinnevisjukhuset, Norrköping
🇸🇪Norrköping, Sweden
Dept. of Internal Medicine, Södersjukhuset
🇸🇪Stockholm, Sweden
Dept. of Anaesthesia and Intensive Care, Skånes Universitetssjukhus (SUS) Malmö
🇸🇪Malmö, Sweden
Dept. of Intensive Care Medicine, Bern University Hospital (Inselspital)
🇨🇭Bern, Switzerland
Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Solna
🇸🇪Stockholm, Sweden
Dept. of Infectious Diseases, Danderyds Sjukhuset
🇸🇪Stockholm, Sweden
Dept. of Intensive Care, Nordsjællands Hospital - Hillerød, Denmark.
🇩🇰Hillerød, 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
Hvidovre Hospital - Dept of Intensive Care
🇩🇰Hvidovre, Denmark
Hvidovre Hospital - Dept of Pulmonary Medicine
🇩🇰Hvidovre, Denmark
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
Hvidovre Hospital - Dept of Infectious diseases
🇩🇰Hvidovre, 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
Amrita Institute of Medical Sciences
🇮🇳Kochi, India
Bombay Hospital & Medical Research Centre
🇮🇳Mumbai, India
Dept. of Anaesthesia and Intensive Care, Capio St Görans Sjukhus
🇸🇪Stockholm, Sweden
Södersjukhuset
🇸🇪Stockholm, Sweden
Dept. of Infectious Diseases, Karolinska Universitetssjukhuset, Solna
🇸🇪Stockholm, Sweden
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
Symbiosis University Hospital and Research Centre
🇮🇳Pune, India
Rajendra Institute of Medical Sciences
🇮🇳Ranchi, India
Gotri General Hospital
🇮🇳Vadodara, India
Vishwaraj Hospital
🇮🇳Pune, India
Christian Medical College Vellore
🇮🇳Vellore, India
Dept. of Anaesthesia and Intensive Care, Sahlgranska Universitetssjukhuset
🇸🇪Göteborg, Sweden