Hydrocortisone for COVID-19 and Severe Hypoxia

Covid-19 Clinical Trial

— COVID STEROID  

Official title:

Low-dose Hydrocortisone in Patients With COVID-19 and Severe Hypoxia - the COVID STEROID Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04348305
• Other study ID #: RH-ITA-008
• Secondary ID: 2020-001395-15
• Status: Completed
• Phase: Phase 3
• Start date: April 17, 2020
• Est. completion date: September 8, 2021

Study information

• Verified date: September 2021
• Source: Scandinavian Critical Care Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 8, 2021
• Est. primary completion date: September 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Covid-19
• Hypoxia

Intervention

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

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital - Dept of Intensive care	Aarhus
Denmark	Dept of Infectious diseases, Rigshospitalet	Copenhagen
Denmark	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	Køge Hospital	Køge
Denmark	Kolding Hospital	Kolding
Denmark	Dept of Intensive Care, Odense University Hospital	Odense
Denmark	Roskilde Hospital	Roskilde
Denmark	Slagelse Hospital	Slagelse
Denmark	Viborg Hospital	Viborg

Sponsors (5)

Lead Sponsor	Collaborator
Scandinavian Critical Care Trials Group	Aarhus University Hospital, Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Denmark, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days alive without life support at day 28	Days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) from randomisation to day 28	Day 28 after randomisation
Secondary	All-cause mortality at day 28	Death from all causes	Day 28 after randomisation
Secondary	Days alive without life support at day 90	Days alive without life support (i.e. invasive mechanical ventilation, circulatory support or renal replacement therapy) from randomisation to day 90	Day 90 after randomisation
Secondary	All-cause mortality at day 90	Death from all causes	Day 90 after randomisation
Secondary	Number of participants with one or more serious adverse reactions	Defined as new episodes of septic shock, invasive fungal infection, clinically important GI bleeding or anaphylactic reaction	Day 14 after randomisation
Secondary	Days alive and out of hospital at day 90	Number of days alive and out of hospital not limited to the index admission	Day 90 after randomisation
Secondary	All-cause mortality at 1 year after randomisation	Death from all causes	1 year after randomisation
Secondary	Health-related quality of life at 1 year	Assessed by EQ-5D-5L	1 year after randomisation
Secondary	Health-related quality of life at 1 year	Assessed by EQ-VAS	1 year after randomisation

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