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Hydrocortisone for COVID-19 and Severe Hypoxia (COVID STEROID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04348305
Recruitment Status : Active, not recruiting
First Posted : April 16, 2020
Last Update Posted : June 24, 2020
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
University of Copenhagen
Aarhus University Hospital
Information provided by (Responsible Party):
Scandinavian Critical Care Trials Group

Brief Summary:
We aim to assess the benefits and harms of low-dose hydrocortisone in patients with COVID-19 and severe hypoxia.

Condition or disease Intervention/treatment Phase
Covid-19 Hypoxia Drug: Hydrocortisone Drug: Sodium Chloride 9mg/mL Phase 3

Detailed Description:

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic of coronavirus disease (COVID-19) with many patients developing severe hypoxic respiratory failure. Many patients have died, and healthcare systems in several countries have been or will be overwhelmed because of a surge of patients needing hospitalisation and intensive care. There is no proven treatment for COVID-19; the care is supportive, including respiratory and circulatory support. For other patient groups with similar critical illness (acute respiratory disease syndrome and septic shock), corticosteroids are used because they reduce the duration of mechanical ventilation, length of stay in the intensive care unit, and potentially also mortality. Corticosteroids have been used in some patients with COVID-19, but the recommendations in clinical guidelines differ; some suggest their use, others against.

Objectives: We aim to assess the effects of low-dose intravenous hydrocortisone on the number of days alive without life-support in adult patients with COVID-19 and severe hypoxia.

Design: Multicentre, 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: Continuous IV infusion of hydrocortisone 200 mg daily will be given for 7 days in addition to standard care.

Control intervention: Continuous IV infusion of matching placebo (0.9% saline) will be given in addition to standard care (no corticosteroids).

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); days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90 and 1 year; and health-related quality of life at 1 year.

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: Low-dose Hydrocortisone in Patients With COVID-19 and Severe Hypoxia - the COVID STEROID Trial
Actual Study Start Date : April 17, 2020
Estimated Primary Completion Date : March 30, 2021
Estimated Study Completion Date : December 30, 2021


Arm Intervention/treatment
Experimental: Hydrocortisone

Continuous intravenous infusion of hydrocortisone 200 mg over 24 hours (total 104 ml). The trial intervention will be given in addition to standard care.

If continuous intravenous infusion is not possible, we will allow the use of bolus injection of the trial medication (50 mg (10 ml) every 6 hours).

Drug: Hydrocortisone
Continuous infusion: 200 mg (104 ml) every 24 hours, Bolus injections: 50 mg (10 ml) every 6 hours, Total treatment duration: 7 days
Other Name: Solu-cortef

Placebo Comparator: Isotonic Saline

Continuous intravenous infusion of matching isotonic saline (0.9%) placebo at a dose volume of 104 ml over 24 hours in addition to standard care (no corticosteroid treatment).

If continuous intravenous infusion is not possible, we will allow the use of bolus injection of matching saline placebo (10 ml every 6 hours).

Drug: Sodium Chloride 9mg/mL
Continuous infusion: 104 ml every 24 hours, Bolus injections: 10 ml every 6 hours, Total treatment duration: 7 days
Other Name: Isotonic saline




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. All-cause mortality at day 28 [ Time Frame: Day 28 after randomisation ]
    Death from all causes

  2. 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

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

  4. Number of participants with one or more serious adverse reactions [ Time Frame: Day 14 after randomisation ]
    Defined as new episodes of septic shock, invasive fungal infection, clinically important GI bleeding or anaphylactic reaction

  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 1 year after randomisation [ Time Frame: 1 year after randomisation ]
    Death from all causes

  7. Health-related quality of life at 1 year [ Time Frame: 1 year after randomisation ]
    Assessed by EQ-5D-5L

  8. Health-related quality of life at 1 year [ Time Frame: 1 year 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 the following criteria 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 any other indication than COVID-19
  • Invasive mechanical ventilation for more than 48 hours
  • Invasive fungal infection
  • Fertile woman (< 60 years of age) with positive urine human gonadotropin (hCG) or plasma-hCG
  • Known hypersensitivity to hydrocortisone
  • A patient for whom the clinical team has decided not to use invasive mechanical ventilation
  • Previously randomised into the COVID STEROID 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): NCT04348305


Locations
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Denmark
Aarhus University Hospital - Dept of Intensive care
Aarhus, Denmark
Rigshospitalet
Copenhagen, Denmark, DK-2100
Dept of Infectious diseases, Rigshospitalet
Copenhagen, Denmark
Herlev Hospital - Dept. of Intensive Care
Herlev, Denmark
North Zealand Hospital
Hillerød, Denmark
Hvidovre Hospital - Dept of Infectious diseases
Hvidovre, Denmark
Hvidovre Hospital - Dept of Intensive Care
Hvidovre, Denmark
Hvidovre Hospital - Dept of Pulmonary Medicine
Hvidovre, Denmark
Kolding Hospital
Kolding, Denmark
Køge Hospital
Køge, Denmark
Dept of Intensive Care, Odense University Hospital
Odense, Denmark
Roskilde Hospital
Roskilde, Denmark
Slagelse Hospital
Slagelse, Denmark
Viborg Hospital
Viborg, Denmark
Sponsors and Collaborators
Scandinavian Critical Care Trials Group
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
University of Copenhagen
Aarhus University Hospital
Investigators
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Study Chair: Anders Perner, MD, PhD Rigshospitalet, Denmark
Additional Information:
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Responsible Party: Scandinavian Critical Care Trials Group
ClinicalTrials.gov Identifier: NCT04348305    
Other Study ID Numbers: RH-ITA-008
2020-001395-15 ( EudraCT Number )
First Posted: April 16, 2020    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: June 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-trial/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypoxia
Signs and Symptoms, Respiratory
Signs and Symptoms
Hydrocortisone
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents