COVID STEROID: Hydrocortisone for COVID-19 and Severe Hypoxia

Sponsor
Scandinavian Critical Care Trials Group (Other)
Overall Status
Completed
CT.gov ID
NCT04348305
Collaborator
Rigshospitalet, Denmark (Other), Copenhagen Trial Unit, Center for Clinical Intervention Research (Other), University of Copenhagen (Other), Aarhus University Hospital (Other)
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Study Details

Study Description

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
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%.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 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 :
Apr 17, 2020
Actual Primary Completion Date :
Sep 10, 2020
Actual Study Completion Date :
Sep 8, 2021

Arms and Interventions

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 Names:
  • 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 Names:
  • Isotonic saline
  • Outcome Measures

    Primary Outcome Measures

    1. Days alive without life support at day 28 [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 [Day 28 after randomisation]

      Death from all causes

    2. Days alive without life support at day 90 [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 [Day 90 after randomisation]

      Death from all causes

    4. Number of participants with one or more serious adverse reactions [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 [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 [1 year after randomisation]

      Death from all causes

    7. Health-related quality of life at 1 year [1 year after randomisation]

      Assessed by EQ-5D-5L

    8. Health-related quality of life at 1 year [1 year after randomisation]

      Assessed by EQ-VAS

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aarhus University Hospital - Dept of Intensive care Aarhus Denmark
    2 Rigshospitalet Copenhagen Denmark DK-2100
    3 Dept of Infectious diseases, Rigshospitalet Copenhagen Denmark
    4 Herlev Hospital - Dept. of Intensive Care Herlev Denmark
    5 North Zealand Hospital Hillerød Denmark
    6 Hvidovre Hospital - Dept of Infectious diseases Hvidovre Denmark
    7 Hvidovre Hospital - Dept of Intensive Care Hvidovre Denmark
    8 Hvidovre Hospital - Dept of Pulmonary Medicine Hvidovre Denmark
    9 Kolding Hospital Kolding Denmark
    10 Køge Hospital Køge Denmark
    11 Dept of Intensive Care, Odense University Hospital Odense Denmark
    12 Roskilde Hospital Roskilde Denmark
    13 Slagelse Hospital Slagelse Denmark
    14 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

    • Study Chair: Anders Perner, MD, PhD, Rigshospitalet, Denmark

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Scandinavian Critical Care Trials Group
    ClinicalTrials.gov Identifier:
    NCT04348305
    Other Study ID Numbers:
    • RH-ITA-008
    • 2020-001395-15
    First Posted:
    Apr 16, 2020
    Last Update Posted:
    Sep 21, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 21, 2021