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

NCT ID: NCT04509973

Last Updated: 2022-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-27

Study Completion Date

2022-02-01

Brief Summary

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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

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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

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Covid19 Hypoxia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

ATC code: H02AB02

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.

Group Type ACTIVE_COMPARATOR

Dexamethasone

Intervention Type DRUG

ATC code: H02AB02

Interventions

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Dexamethasone

ATC code: H02AB02

Intervention Type DRUG

Other Intervention Names

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Dexavit

Eligibility Criteria

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Inclusion Criteria

* 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

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Copenhagen Trial Unit, Center for Clinical Intervention Research

OTHER

Sponsor Role collaborator

Centre for Research in Intensive Care (CRIC)

OTHER

Sponsor Role collaborator

Aarhus University Hospital

OTHER

Sponsor Role collaborator

Aalborg University Hospital

OTHER

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

The George Institute for Global Health, Australia

OTHER

Sponsor Role collaborator

Scandinavian Critical Care Trials Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hvidovre Hospital - Dept of Infectious diseases

Hvidovre, , Denmark

Site Status

Hvidovre Hospital - Dept of Intensive Care

Hvidovre, , Denmark

Site Status

Hvidovre Hospital - Dept of Pulmonary Medicine

Hvidovre, , Denmark

Site Status

Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital

Kolding, , Denmark

Site Status

Dept. of Intensive Care, Køge University Hospital

Køge, , Denmark

Site Status

Dept of Intensive Care, Odense University Hospital

Odense, , Denmark

Site Status

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

Aalborg, , Denmark

Site Status

Dept. of Intensive care, Aarhus University Hospital

Aarhus, , Denmark

Site Status

Dept. of Intensive Care, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status

Dept. of Neuroanaesthesiology

Copenhagen, , Denmark

Site Status

Dept. of Thoracic Anaesthesiology, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status

Dept of Infectious diseases, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status

Dept. of Intensive Care, Gentofte Hospital

Hellerup, , Denmark

Site Status

Dept. of Anaesthesia and Intensive Care, Herlev Hospital

Herlev, , Denmark

Site Status

Dept. of Anaesthesia, Regional Hospital West Jutland, Herning

Herning, , Denmark

Site Status

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

Hillerød, , Denmark

Site Status

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

Roskilde, , Denmark

Site Status

Dept. of Anaesthesia, Slagelse Hospital

Slagelse, , Denmark

Site Status

Dept. of Anaesthesia and Intensive Care, Viborg Hospital

Viborg, , Denmark

Site Status

Jawahar Lal Nehru Medical Collega, AMU

Aligarh, , India

Site Status

Apollo Hospital

Chennai, , India

Site Status

Amrita Institute of Medical Sciences

Kochi, , India

Site Status

Bombay Hospital & Medical Research Centre

Mumbai, , India

Site Status

K. J. Somaiya Super Specialty Hospital

Mumbai, , India

Site Status

P. D. Hinduja National Hospital & Medical Research Centre

Mumbai, , India

Site Status

S L Raheja Fortis Hospital

Mumbai, , India

Site Status

Tata Memorial Hospital

Mumbai, , India

Site Status

Wockhardt hospitals

Mumbai, , India

Site Status

Indraprastha Apollo Hospital

New Delhi, , India

Site Status

Max Super Specialty Hospital, Saket

New Delhi, , India

Site Status

Symbiosis University Hospital and Research Centre

Pune, , India

Site Status

Vishwaraj Hospital

Pune, , India

Site Status

Rajendra Institute of Medical Sciences

Ranchi, , India

Site Status

Gotri General Hospital

Vadodara, , India

Site Status

Christian Medical College Vellore

Vellore, , India

Site Status

Dept. of Anaesthesia and Intensive Care, Sahlgranska Universitetssjukhuset

Gothenburg, , Sweden

Site Status

Dept. of Infectious Diseases, Sahlgranska Universitetssjukhuset

Gothenburg, , Sweden

Site Status

Dept. of Anaesthesia and Intensive Care, Universitetssjukhuset i Linköping

Linköping, , Sweden

Site Status

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

Malmo, , Sweden

Site Status

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

Malmo, , Sweden

Site Status

Dept. of Anaesthesia and Intensive Care, Vrinnevisjukhuset, Norrköping

Norrköping, , Sweden

Site Status

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

Stockholm, , Sweden

Site Status

Dept. of Anaesthesia and Intensive Care, Danderyds Sjukhuset

Stockholm, , Sweden

Site Status

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

Stockholm, , Sweden

Site Status

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

Stockholm, , Sweden

Site Status

Dept. of Cardiology, Södersjukhuset

Stockholm, , Sweden

Site Status

Dept. of Infectious Diseases, Danderyds Sjukhuset

Stockholm, , Sweden

Site Status

Dept. of Infectious Diseases, Karolinska Universitetssjukhuset, Solna

Stockholm, , Sweden

Site Status

Dept. of Infectious Diseases, Södersjukhuset

Stockholm, , Sweden

Site Status

Dept. of Internal Medicine, Danderyds Sjukhuset

Stockholm, , Sweden

Site Status

Dept. of Internal Medicine, Södersjukhuset

Stockholm, , Sweden

Site Status

Södersjukhuset

Stockholm, , Sweden

Site Status

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

Bern, , Switzerland

Site Status

Countries

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Denmark India Sweden Switzerland

References

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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.

Reference Type DERIVED
PMID: 37316785 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35359168 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35349129 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34757439 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34673895 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33583027 (View on PubMed)

Related Links

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Other Identifiers

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2020-003363-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2020-07-16

Identifier Type: OTHER

Identifier Source: secondary_id

H-20051056

Identifier Type: OTHER

Identifier Source: secondary_id

RH-ITA-009

Identifier Type: -

Identifier Source: org_study_id

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