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

NCT04509973 | Completed Phase 3 DMC

• 4 other identifiers: RH-ITA-0092020-003363-252020-07-16H-20051056
• Study Type: interventional
• Target: 1,000
• Locations: 4 countries
• Sites: 53

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.

Conditions

Covid19; Hypoxia

Keywords

Randomised clinical trial; COVID-19; Hypoxia; Corticosteroids

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of participants with one or more serious adverse reactions

  Day 28 after randomisation

• All-cause mortality at day 28

  Day 28 after randomisation

• All-cause mortality at day 90

  Day 90 after randomisation

• Days alive without life support at day 90

  Day 90 after randomisation

• Days alive and out of hospital at day 90

  Day 90 after randomisation

Study Arms (2)

Dexamethasone 12 mg

EXPERIMENTAL

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

Dexamethasone 6 mg

ACTIVE COMPARATOR

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

Interventions

Dexamethasone DRUG

ATC code: H02AB02

Also known as: Dexavit

Dexamethasone 12 mg; Dexamethasone 6 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (53)

Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital, Denmark.

Aalborg, Denmark

Location

Dept. of Intensive care, Aarhus University Hospital

Aarhus, Denmark

Location

Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept. of Neuroanaesthesiology

Copenhagen, 2100, Denmark

Location

Dept. of Thoracic Anaesthesiology, Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept of Infectious diseases, Copenhagen University Hospital, Rigshospitalet

Copenhagen, Denmark

Location

Dept. of Intensive Care, Gentofte Hospital

Hellerup, 2900, Denmark

Location

Dept. of Anaesthesia and Intensive Care, Herlev Hospital

Herlev, 2730, Denmark

Location

Dept. of Anaesthesia, Regional Hospital West Jutland, Herning

Herning, 7400, Denmark

Location

Dept. of Intensive Care, Nordsjællands Hospital - Hillerød, Denmark.

Hillerød, Denmark

Location

Hvidovre Hospital - Dept of Infectious diseases

Hvidovre, Denmark

Location

Hvidovre Hospital - Dept of Intensive Care

Hvidovre, Denmark

Location

Hvidovre Hospital - Dept of Pulmonary Medicine

Hvidovre, Denmark

Location

Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital

Kolding, Denmark

Location

Dept. of Intensive Care, Køge University Hospital

Køge, 4600, Denmark

Location

Dept of Intensive Care, Odense University Hospital

Odense, Denmark

Location

Dept. of Anaesthesia and Intensive Care, Zealand University Hospital Roskilde

Roskilde, Denmark

Location

Dept. of Anaesthesia, Slagelse Hospital

Slagelse, 4200, Denmark

Location

Dept. of Anaesthesia and Intensive Care, Viborg Hospital

Viborg, Denmark

Location

Jawahar Lal Nehru Medical Collega, AMU

Aligarh, India

Location

Apollo Hospital

Chennai, India

Location

Amrita Institute of Medical Sciences

Kochi, India

Location

Bombay Hospital & Medical Research Centre

Mumbai, India

Location

K. J. Somaiya Super Specialty Hospital

Mumbai, India

Location

P. D. Hinduja National Hospital & Medical Research Centre

Mumbai, India

Location

S L Raheja Fortis Hospital

Mumbai, India

Location

Tata Memorial Hospital

Mumbai, India

Location

Wockhardt hospitals

Mumbai, India

Location

Indraprastha Apollo Hospital

New Delhi, India

Location

Max Super Specialty Hospital, Saket

New Delhi, India

Location

Symbiosis University Hospital and Research Centre

Pune, India

Location

Vishwaraj Hospital

Pune, India

Location

Rajendra Institute of Medical Sciences

Ranchi, India

Location

Gotri General Hospital

Vadodara, India

Location

Christian Medical College Vellore

Vellore, India

Location

Dept. of Anaesthesia and Intensive Care, Sahlgranska Universitetssjukhuset

Gothenburg, Sweden

Location

Dept. of Infectious Diseases, Sahlgranska Universitetssjukhuset

Gothenburg, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Universitetssjukhuset i Linköping

Linköping, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Skånes Universitetssjukhus (SUS) Malmö

Malmo, Sweden

Location

Dept. of Infectious Diseases, Skånes Universitetssjukhus (SUS) Malmö

Malmo, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Vrinnevisjukhuset, Norrköping

Norrköping, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Capio St Görans Sjukhus

Stockholm, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Danderyds Sjukhuset

Stockholm, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Huddinge

Stockholm, Sweden

Location

Dept. of Anaesthesia and Intensive Care, Karolinska Universitetssjukhuset, Solna

Stockholm, Sweden

Location

Dept. of Cardiology, Södersjukhuset

Stockholm, Sweden

Location

Dept. of Infectious Diseases, Danderyds Sjukhuset

Stockholm, Sweden

Location

Dept. of Infectious Diseases, Karolinska Universitetssjukhuset, Solna

Stockholm, Sweden

Location

Dept. of Infectious Diseases, Södersjukhuset

Stockholm, Sweden

Location

Dept. of Internal Medicine, Danderyds Sjukhuset

Stockholm, Sweden

Location

Dept. of Internal Medicine, Södersjukhuset

Stockholm, Sweden

Location

Södersjukhuset

Stockholm, Sweden

Location

Dept. of Intensive Care Medicine, Bern University Hospital (Inselspital)

Bern, Switzerland

Location

Related Publications (6)

• Granholm A, Kaas-Hansen BS, Lange T, Munch MW, Harhay MO, Zampieri FG, Perner A, Moller MH, Jensen AKG. Use of days alive without life support and similar count outcomes in randomised clinical trials - an overview and comparison of methodological choices and analysis methods. BMC Med Res Methodol. 2023 Jun 14;23(1):139. doi: 10.1186/s12874-023-01963-z.

  PMID: 37316785 DERIVED

• Granholm A, Kjaer MN, Munch MW, Myatra SN, Vijayaraghavan BKT, Cronhjort M, Wahlin RR, Jakob SM, Cioccari L, Vesterlund GK, Meyhoff TS, Helleberg M, Moller MH, Benfield T, Venkatesh B, Hammond NE, Micallef S, Bassi A, John O, Jha V, Kristiansen KT, Ulrik CS, Jorgensen VL, Smitt M, Bestle MH, Andreasen AS, Poulsen LM, Rasmussen BS, Brochner AC, Strom T, Moller A, Khan MS, Padmanaban A, Divatia JV, Saseedharan S, Borawake K, Kapadia F, Dixit S, Chawla R, Shukla U, Amin P, Chew MS, Wamberg CA, Bose N, Shah MS, Darfelt IS, Gluud C, Lange T, Perner A. Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia. Intensive Care Med. 2022 May;48(5):580-589. doi: 10.1007/s00134-022-06677-2. Epub 2022 Mar 31.

  PMID: 35359168 DERIVED

• Durr KM, Hendin A, Perry JJ. Effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: the COVID STEROID 2 randomized trial. CJEM. 2022 Apr;24(3):266-267. doi: 10.1007/s43678-022-00293-1. Epub 2022 Mar 29. No abstract available.

  PMID: 35349129 DERIVED

• Granholm A, Munch MW, Myatra SN, Vijayaraghavan BKT, Cronhjort M, Wahlin RR, Jakob SM, Cioccari L, Kjaer MN, Vesterlund GK, Meyhoff TS, Helleberg M, Moller MH, Benfield T, Venkatesh B, Hammond NE, Micallef S, Bassi A, John O, Jha V, Kristiansen KT, Ulrik CS, Jorgensen VL, Smitt M, Bestle MH, Andreasen AS, Poulsen LM, Rasmussen BS, Brochner AC, Strom T, Moller A, Khan MS, Padmanaban A, Divatia JV, Saseedharan S, Borawake K, Kapadia F, Dixit S, Chawla R, Shukla U, Amin P, Chew MS, Wamberg CA, Gluud C, Lange T, Perner A. Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial. Intensive Care Med. 2022 Jan;48(1):45-55. doi: 10.1007/s00134-021-06573-1. Epub 2021 Nov 10.

  PMID: 34757439 DERIVED

• COVID STEROID 2 Trial Group; Munch MW, Myatra SN, Vijayaraghavan BKT, Saseedharan S, Benfield T, Wahlin RR, Rasmussen BS, Andreasen AS, Poulsen LM, Cioccari L, Khan MS, Kapadia F, Divatia JV, Brochner AC, Bestle MH, Helleberg M, Michelsen J, Padmanaban A, Bose N, Moller A, Borawake K, Kristiansen KT, Shukla U, Chew MS, Dixit S, Ulrik CS, Amin PR, Chawla R, Wamberg CA, Shah MS, Darfelt IS, Jorgensen VL, Smitt M, Granholm A, Kjaer MN, Moller MH, Meyhoff TS, Vesterlund GK, Hammond NE, Micallef S, Bassi A, John O, Jha A, Cronhjort M, Jakob SM, Gluud C, Lange T, Kadam V, Marcussen KV, Hollenberg J, Hedman A, Nielsen H, Schjorring OL, Jensen MQ, Leistner JW, Jonassen TB, Kristensen CM, Clapp EC, Hjortso CJS, Jensen TS, Halstad LS, Bak ERB, Zaabalawi R, Metcalf-Clausen M, Abdi S, Hatley EV, Aksnes TS, Gleipner-Andersen E, Alarcon AF, Yamin G, Heymowski A, Berggren A, La Cour K, Weihe S, Pind AH, Engstrom J, Jha V, Venkatesh B, Perner A. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial. JAMA. 2021 Nov 9;326(18):1807-1817. doi: 10.1001/jama.2021.18295.

  PMID: 34673895 DERIVED

• Granholm A, Munch MW, Myatra SN, Vijayaraghavan BKT, Cronhjort M, Wahlin RR, Jakob SM, Cioccari L, Kjaer MN, Vesterlund GK, Meyhoff TS, Helleberg M, Moller MH, Benfield T, Venkatesh B, Hammond N, Micallef S, Bassi A, John O, Jha V, Kristiansen KT, Ulrik CS, Jorgensen VL, Smitt M, Bestle MH, Andreasen AS, Poulsen LM, Rasmussen BS, Brochner AC, Strom T, Moller A, Khan MS, Padmanaban A, Divatia JV, Saseedharan S, Borawake K, Kapadia F, Dixit S, Chawla R, Shukla U, Amin P, Chew MS, Gluud C, Lange T, Perner A. Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis. Acta Anaesthesiol Scand. 2021 May;65(5):702-710. doi: 10.1111/aas.13793. Epub 2021 Feb 25.

  PMID: 33583027 DERIVED

Related Links

• Trial website

MeSH Terms

Conditions

COVID-19; Hypoxia

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 12, 2020
• Study Start: August 27, 2020
• Primary Completion: June 17, 2021
• Study Completion: February 1, 2022
• Last Updated: February 24, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediate sharing of protocol, SAP and ICF. CSR will be shared no later than 6 months after last-patient-last-visit
• Access Criteria: Contact to the trial management committee

Locations

DK (19); IN (16); SE (17); CH (1)