COVIDSTEROID2: Higher vs. Lower Doses of Dexamethasone for COVID-19 and Severe Hypoxia

• Sponsor: Scandinavian Critical Care Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT04509973
• Collaborator: Copenhagen Trial Unit, Center for Clinical Intervention Research (Other), Centre for Research in Intensive Care (CRIC) (Other), Aarhus University Hospital (Other), Aalborg University Hospital (Other), Rigshospitalet, Denmark (Other), The George Institute for Global Health, Australia (Other)
• Enrollment: 1,000
• Locations: 53
• Arms: 2
• Actual Duration (Months): 17.2
• Patients Per Site: 18.9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19; Hypoxia	Drug: Dexamethasone	Phase 3

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%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Higher vs. Lower Doses of Dexamethasone in Patients With COVID-19 and Severe Hypoxia
• Actual Study Start Date: Aug 27, 2020
• Actual Primary Completion Date: Jun 17, 2021
• Actual Study Completion Date: Feb 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexamethasone 12 mg 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.	Drug: Dexamethasone; ATC code: H02AB02; Other Names: Dexavit
Active Comparator: Dexamethasone 6 mg 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.	Drug: Dexamethasone; ATC code: H02AB02; Other Names: Dexavit

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. All-cause mortality at day 28 [Day 28 after randomisation]

   Death from all causes

3. All-cause mortality at day 90 [Day 90 after randomisation]

   Death from all causes

4. 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

5. 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

6. All-cause mortality at day 180 [Day 180 after randomisation]

   Death from all causes

7. Health-related quality of life at day 180 [Day 180 after randomisation]

   Assessed by EQ-5D-5L

8. Health-related quality of life at day 180 [Day 180 after randomisation]

   Assessed by EQ-VAS

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital, Denmark.	Aalborg		Denmark
2	Dept. of Intensive care, Aarhus University Hospital	Aarhus		Denmark
3	Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet	Copenhagen		Denmark	2100
4	Dept. of Neuroanaesthesiology	Copenhagen		Denmark	2100
5	Dept. of Thoracic Anaesthesiology, Copenhagen University Hospital, Rigshospitalet	Copenhagen		Denmark	2100
6	Dept of Infectious diseases, Copenhagen University Hospital, Rigshospitalet	Copenhagen		Denmark
7	Dept. of Intensive Care, Gentofte Hospital	Hellerup		Denmark	2900
8	Dept. of Anaesthesia and Intensive Care, Herlev Hospital	Herlev		Denmark	2730
9	Dept. of Anaesthesia, Regional Hospital West Jutland, Herning	Herning		Denmark	7400
10	Dept. of Intensive Care, Nordsjællands Hospital - Hillerød, Denmark.	Hillerød		Denmark
11	Hvidovre Hospital - Dept of Infectious diseases	Hvidovre		Denmark
12	Hvidovre Hospital - Dept of Intensive Care	Hvidovre		Denmark
13	Hvidovre Hospital - Dept of Pulmonary Medicine	Hvidovre		Denmark
14	Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital	Kolding		Denmark
15	Dept. of Intensive Care, Køge University Hospital	Køge		Denmark	4600
16	Dept of Intensive Care, Odense University Hospital	Odense		Denmark
17	Dept. of Anaesthesia and Intensive Care, Zealand University Hospital Roskilde	Roskilde		Denmark
18	Dept. of Anaesthesia, Slagelse Hospital	Slagelse		Denmark	4200
19	Dept. of Anaesthesia and Intensive Care, Viborg Hospital	Viborg		Denmark
20	Jawahar Lal Nehru Medical Collega, AMU	Aligarh		India
21	Apollo Hospital	Chennai		India
22	Amrita Institute of Medical Sciences	Kochi		India
23	Bombay Hospital & Medical Research Centre	Mumbai		India
24	K. J. Somaiya Super Specialty Hospital	Mumbai		India
25	P. D. Hinduja National Hospital & Medical Research Centre	Mumbai		India
26	S L Raheja Fortis Hospital	Mumbai		India
27	Tata Memorial Hospital	Mumbai		India
28	Wockhardt hospitals	Mumbai		India
29	Indraprastha Apollo Hospital	New Delhi		India
30	Max Super Specialty Hospital, Saket	New Delhi		India
31	Symbiosis University Hospital and Research Centre	Pune		India
32	Vishwaraj Hospital	Pune		India
33	Rajendra Institute of Medical Sciences	Ranchi		India
34	Gotri General Hospital	Vadodara		India
35	Christian Medical College Vellore	Vellore		India
36	Dept. of Anaesthesia and Intensive Care, Sahlgranska Universitetssjukhuset	Göteborg		Sweden
37	Dept. of Infectious Diseases, Sahlgranska Universitetssjukhuset	Göteborg		Sweden
38	Dept. of Anaesthesia and Intensive Care, Universitetssjukhuset i Linköping	Linköping		Sweden
39	Dept. of Anaesthesia and Intensive Care, Skånes Universitetssjukhus (SUS) Malmö	Malmö		Sweden
40	Dept. of Infectious Diseases, Skånes Universitetssjukhus (SUS) Malmö	Malmö		Sweden
41	Dept. of Anaesthesia and Intensive Care, Vrinnevisjukhuset, Norrköping	Norrköping		Sweden
42	Dept. of Anaesthesia and Intensive Care, Capio St Görans Sjukhus	Stockholm		Sweden
43	Dept. of Anaesthesia and Intensive Care, Danderyds Sjukhuset	Stockholm		Sweden
44	Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Huddinge	Stockholm		Sweden
45	Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Solna	Stockholm		Sweden
46	Dept. of Cardiology, Södersjukhuset	Stockholm		Sweden
47	Dept. of Infectious Diseases, Danderyds Sjukhuset	Stockholm		Sweden
48	Dept. of Infectious Diseases, Karolinska Universitetssjukhuset, Solna	Stockholm		Sweden
49	Dept. of Infectious Diseases, Södersjukhuset	Stockholm		Sweden
50	Dept. of Internal Medicine, Danderyds Sjukhuset	Stockholm		Sweden
51	Dept. of Internal Medicine, Södersjukhuset	Stockholm		Sweden
52	Södersjukhuset	Stockholm		Sweden
53	Dept. of Intensive Care Medicine, Bern University Hospital (Inselspital)	Bern		Switzerland

Sponsors and Collaborators

• Scandinavian Critical Care Trials Group
• 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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Trial website

Publications

None provided.

• Responsible Party: Scandinavian Critical Care Trials Group
• ClinicalTrials.gov Identifier: NCT04509973
• Other Study ID Numbers: RH-ITA-009; 2020-003363-25; 2020-07-16; H-20051056
• First Posted: Aug 12, 2020
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Scandinavian Critical Care Trials Group: Randomised clinical trial; COVID-19; Hypoxia; Corticosteroids
• Additional relevant MeSH terms: COVID-19; Hypoxia; Dexamethasone

Study Results

No Results Posted as of Feb 24, 2022