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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

Tracking Information
First Submitted Date  ICMJE August 11, 2020
First Posted Date  ICMJE August 12, 2020
Last Update Posted Date September 1, 2020
Actual Study Start Date  ICMJE August 27, 2020
Estimated Primary Completion Date September 17, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • 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
  • All-cause mortality at day 28 [ Time Frame: Day 28 after randomisation ]
    Death from all causes
  • All-cause mortality at day 90 [ Time Frame: Day 90 after randomisation ]
    Death from all causes
  • 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
  • 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
  • All-cause mortality at day 180 [ Time Frame: Day 180 after randomisation ]
    Death from all causes
  • Health-related quality of life at day 180 [ Time Frame: Day 180 after randomisation ]
    Assessed by EQ-5D-5L
  • Health-related quality of life at day 180 [ Time Frame: Day 180 after randomisation ]
    Assessed by EQ-VAS
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Higher vs. Lower Doses of Dexamethasone for COVID-19 and Severe Hypoxia
Official Title  ICMJE Higher vs. Lower Doses of Dexamethasone in Patients With COVID-19 and Severe Hypoxia
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • Hypoxia
Intervention  ICMJE Drug: Dexamethasone
ATC code: H02AB02
Other Name: Dexavit
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Dexamethasone
  • 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.
    Intervention: Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 11, 2020)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 17, 2022
Estimated Primary Completion Date September 17, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anders Perner, MD, PhD, Professor +4535458333 anders.perner@regionh.dk
Contact: Marie Warrer Petersen, MD +4535457236 marie.warrer.petersen.01@regionh.dk
Listed Location Countries  ICMJE Denmark,   India,   Sweden,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04509973
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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/
Responsible Party Scandinavian Critical Care Trials Group
Study Sponsor  ICMJE Scandinavian Critical Care Trials Group
Collaborators  ICMJE
  • 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  ICMJE Not Provided
PRS Account Scandinavian Critical Care Trials Group
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP