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

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ClinicalTrials.gov Identifier: NCT04509973
Recruitment Status : Recruiting
First Posted : August 12, 2020
Last Update Posted : September 1, 2020
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Scandinavian Critical Care Trials Group

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%.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 27, 2020
Estimated Primary Completion Date : September 17, 2021
Estimated Study Completion Date : February 17, 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Dexavit




Primary Outcome Measures :
  1. Days alive without life support at day 28 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 28 after randomisation ]
    Death from all causes

  3. All-cause mortality at day 90 [ Time Frame: Day 90 after randomisation ]
    Death from all causes

  4. Days alive without life support at day 90 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 180 after randomisation ]
    Death from all causes

  7. Health-related quality of life at day 180 [ Time Frame: Day 180 after randomisation ]
    Assessed by EQ-5D-5L

  8. Health-related quality of life at day 180 [ Time Frame: Day 180 after randomisation ]
    Assessed by EQ-VAS



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04509973


Contacts
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Contact: Anders Perner, MD, PhD, Professor +4535458333 anders.perner@regionh.dk
Contact: Marie Warrer Petersen, MD +4535457236 marie.warrer.petersen.01@regionh.dk

Locations
Show Show 53 study locations
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
Additional Information:
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Responsible Party: Scandinavian Critical Care Trials Group
ClinicalTrials.gov Identifier: NCT04509973    
Other Study ID Numbers: RH-ITA-009
2020-003363-25 ( EudraCT Number )
2020-07-16 ( Other Identifier: Danish Medicines Agency )
H-20051056 ( Other Identifier: Ethic committee of the Capital Region, DK )
First Posted: August 12, 2020    Key Record Dates
Last Update Posted: September 1, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Fully de-identified IPD will be shared after the approval by the the trial management committee
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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
URL: http://www.cric.nu/covid-steroid-2/

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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:
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Hypoxia
Signs and Symptoms, Respiratory
Dexamethasone
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents