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Covid19Phase 3COVIDSTEROID2NCT04509973

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

A Phase 3 study testing Dexamethasone in people with Covid19 and Hypoxia, run by Scandinavian Critical Care Trials Group at 53 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19, Hypoxia
What is being tested?
Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,000 participants
Where
53 sitesin 4 countries
Study dates
27 Aug 2020to 1 Feb 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

53 sites in 4 countries.

53 sites in 4 countries

Denmark19 sites

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

    Aalborg

  • Dept. of Intensive care, Aarhus University Hospital

    Aarhus

  • Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet

    Copenhagen, 2100

  • Dept. of Neuroanaesthesiology

    Copenhagen, 2100

  • Dept. of Thoracic Anaesthesiology, Copenhagen University Hospital, Rigshospitalet

    Copenhagen, 2100

  • Dept of Infectious diseases, Copenhagen University Hospital, Rigshospitalet

    Copenhagen

  • Dept. of Intensive Care, Gentofte Hospital

    Hellerup, 2900

  • Dept. of Anaesthesia and Intensive Care, Herlev Hospital

    Herlev, 2730

  • Dept. of Anaesthesia, Regional Hospital West Jutland, Herning

    Herning, 7400

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

    Hillerød

  • Hvidovre Hospital - Dept of Infectious diseases

    Hvidovre

  • Hvidovre Hospital - Dept of Intensive Care

    Hvidovre

  • Hvidovre Hospital - Dept of Pulmonary Medicine

    Hvidovre

  • Dept. of Intensive Care, Køge University Hospital

    Køge, 4600

  • Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital

    Kolding

  • Dept of Intensive Care, Odense University Hospital

    Odense

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

    Roskilde

  • Dept. of Anaesthesia, Slagelse Hospital

    Slagelse, 4200

  • Dept. of Anaesthesia and Intensive Care, Viborg Hospital

    Viborg

Other trials in Denmark

Sweden17 sites

  • Dept. of Anaesthesia and Intensive Care, Sahlgranska Universitetssjukhuset

    Gothenburg

  • Dept. of Infectious Diseases, Sahlgranska Universitetssjukhuset

    Gothenburg

  • Dept. of Anaesthesia and Intensive Care, Universitetssjukhuset i Linköping

    Linköping

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

    Malmö

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

    Malmö

  • Dept. of Anaesthesia and Intensive Care, Vrinnevisjukhuset, Norrköping

    Norrköping

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

    Stockholm

  • Dept. of Anaesthesia and Intensive Care, Danderyds Sjukhuset

    Stockholm

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

    Stockholm

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

    Stockholm

  • Dept. of Cardiology, Södersjukhuset

    Stockholm

  • Dept. of Infectious Diseases, Danderyds Sjukhuset

    Stockholm

  • Dept. of Infectious Diseases, Karolinska Universitetssjukhuset, Solna

    Stockholm

  • Dept. of Infectious Diseases, Södersjukhuset

    Stockholm

  • Dept. of Internal Medicine, Danderyds Sjukhuset

    Stockholm

  • Dept. of Internal Medicine, Södersjukhuset

    Stockholm

  • Södersjukhuset

    Stockholm

Other trials in Sweden

India16 sites

  • Jawahar Lal Nehru Medical Collega, AMU

    Aligarh

  • Apollo Hospital

    Chennai

  • Amrita Institute of Medical Sciences

    Kochi

  • Bombay Hospital & Medical Research Centre

    Mumbai

  • K. J. Somaiya Super Specialty Hospital

    Mumbai

  • P. D. Hinduja National Hospital & Medical Research Centre

    Mumbai

  • S L Raheja Fortis Hospital

    Mumbai

  • Tata Memorial Hospital

    Mumbai

  • Wockhardt hospitals

    Mumbai

  • Indraprastha Apollo Hospital

    New Delhi

  • Max Super Specialty Hospital, Saket

    New Delhi

  • Symbiosis University Hospital and Research Centre

    Pune

  • Vishwaraj Hospital

    Pune

  • Rajendra Institute of Medical Sciences

    Ranchi

  • Gotri General Hospital

    Vadodara

  • Christian Medical College Vellore

    Vellore

Other trials in India

Switzerland1 site

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

    Bern

Other trials in Switzerland

About this study

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

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.

Read the 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%.

Conditions
Covid19, Hypoxia
Being tested
Dexamethasone
Keywords
Randomised clinical trial, COVID-19, Hypoxia, Corticosteroids
Medical subject headings
COVID-19, Hypoxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04509973
Study groupRoleWhat they receive
Dexamethasone 12 mgExperimentalIntravenous 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.
Receives: Drug: Dexamethasone
Dexamethasone 6 mgActive comparatorIntravenous 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.
Receives: Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Day 28 after randomisation

Secondary outcomes (8)

  1. 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

    Measured: Day 28 after randomisation

  2. All-cause mortality at day 28

    Death from all causes

    Measured: Day 28 after randomisation

  3. All-cause mortality at day 90

    Death from all causes

    Measured: Day 90 after randomisation

  4. 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

    Measured: Day 90 after randomisation

  5. Days alive and out of hospital at day 90

    Number of days alive and out of hospital not limited to the index admission

    Measured: Day 90 after randomisation

  6. All-cause mortality at day 180

    Death from all causes

    Measured: Day 180 after randomisation

  7. Health-related quality of life at day 180

    Assessed by EQ-5D-5L

    Measured: Day 180 after randomisation

  8. Health-related quality of life at day 180

    Assessed by EQ-VAS

    Measured: Day 180 after randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2020
  2. Study start27 Aug 2020
  3. Primary completion17 Jun 2021
  4. Study completion1 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,000 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04509973
Sponsor's protocol ID
RH-ITA-009
Other IDs
2020-003363-25, 2020-07-16, H-20051056
Acronym
COVIDSTEROID2
Status last verified
Feb 2022
First submitted
11 Aug 2020
Last updated
24 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Fully de-identified IPD will be shared after the approval by the the trial management committee

Publications

  • 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.

    PubMed 37316785

  • 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.

    PubMed 35359168

  • 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.

    PubMed 35349129

  • 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.

    PubMed 34757439

  • 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.

    PubMed 34673895

  • 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.

    PubMed 33583027

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dexamethasone in people with Covid19 and Hypoxia, run by Scandinavian Critical Care Trials Group at 53 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in Denmark, Sweden, India, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Days alive without life support at day 28 (time frame: Day 28 after randomisation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04509973, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2022.

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