Higher vs. Lower Doses of Dexamethasone for COVID-19 and Severe Hypoxia

Covid19 Clinical Trial

— COVIDSTEROID2  

Official title:

Higher vs. Lower Doses of Dexamethasone in Patients With COVID-19 and Severe Hypoxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04509973
• Other study ID #: RH-ITA-009
• Secondary ID: 2020-003363-2520
• Status: Completed
• Phase: Phase 3
• Start date: August 27, 2020
• Est. completion date: February 1, 2022

Study information

• Verified date: February 2022
• Source: Scandinavian Critical Care Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: February 1, 2022
• Est. primary completion date: June 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Hypoxia

Intervention

Drug:
• Dexamethasone
ATC code: H02AB02

Locations

Country	Name	City	State
Denmark	Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital, Denmark.	Aalborg
Denmark	Dept. of Intensive care, Aarhus University Hospital	Aarhus
Denmark	Dept of Infectious diseases, Copenhagen University Hospital, Rigshospitalet	Copenhagen
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 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 Intensive Care, Køge University Hospital	Køge
Denmark	Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital	Kolding
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
India	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
Sweden	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
Switzerland	Dept. of Intensive Care Medicine, Bern University Hospital (Inselspital)	Bern

Sponsors (7)

Lead Sponsor	Collaborator
Scandinavian Critical Care Trials Group	Aalborg University Hospital, Aarhus University Hospital, Centre for Research in Intensive Care (CRIC), Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Denmark, The George Institute for Global Health, Australia

Countries where clinical trial is conducted

Denmark,  India,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days alive without life support at day 28	Days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) from randomisation to day 28	Day 28 after randomisation
Secondary	Number of participants with one or more serious adverse reactions	Serious adverse reactions defined as new episodes of septic shock, invasive fungal infection, clinically important gastrointestinal bleeding or anaphylactic reaction	Day 28 after randomisation
Secondary	All-cause mortality at day 28	Death from all causes	Day 28 after randomisation
Secondary	All-cause mortality at day 90	Death from all causes	Day 90 after randomisation
Secondary	Days alive without life support at day 90	Days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) from randomisation to day 90	Day 90 after randomisation
Secondary	Days alive and out of hospital at day 90	Number of days alive and out of hospital not limited to the index admission	Day 90 after randomisation
Secondary	All-cause mortality at day 180	Death from all causes	Day 180 after randomisation
Secondary	Health-related quality of life at day 180	Assessed by EQ-5D-5L	Day 180 after randomisation
Secondary	Health-related quality of life at day 180	Assessed by EQ-VAS	Day 180 after randomisation

External Links

•   Trial website