Hydrocortisone for COVID-19 and Severe Hypoxia

NCT04348305 | Completed Phase 3 DMC

• 2 other identifiers: RH-ITA-0082020-001395-15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 14

Brief Summary

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

Conditions

Covid-19; Hypoxia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• All-cause mortality at day 28

  Day 28 after randomisation

• Days alive without life support at day 90

  Day 90 after randomisation

• All-cause mortality at day 90

  Day 90 after randomisation

• Number of participants with one or more serious adverse reactions

  Day 14 after randomisation

• Days alive and out of hospital at day 90

  Day 90 after randomisation

Study Arms (2)

Hydrocortisone

EXPERIMENTAL

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

Isotonic Saline

PLACEBO COMPARATOR

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

Interventions

Hydrocortisone DRUG

Continuous infusion: 200 mg (104 ml) every 24 hours, Bolus injections: 50 mg (10 ml) every 6 hours, Total treatment duration: 7 days

Also known as: Solu-cortef

Hydrocortisone

Sodium Chloride 9mg/mL DRUG

Continuous infusion: 104 ml every 24 hours, Bolus injections: 10 ml every 6 hours, Total treatment duration: 7 days

Also known as: Isotonic saline

Isotonic Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Scandinavian Critical Care Trials Group: lead
• Rigshospitalet, Denmark: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator
• University of Copenhagen: collaborator
• Aarhus University Hospital: collaborator

Study Sites (14)

Aarhus University Hospital - Dept of Intensive care

Aarhus, Denmark

Location

Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Dept of Infectious diseases, Rigshospitalet

Copenhagen, Denmark

Location

Herlev Hospital - Dept. of Intensive Care

Herlev, Denmark

Location

North Zealand Hospital

Hillerød, Denmark

Location

Hvidovre Hospital - Dept of Infectious diseases

Hvidovre, Denmark

Location

Hvidovre Hospital - Dept of Intensive Care

Hvidovre, Denmark

Location

Hvidovre Hospital - Dept of Pulmonary Medicine

Hvidovre, Denmark

Location

Kolding Hospital

Kolding, Denmark

Location

Køge Hospital

Køge, Denmark

Location

Dept of Intensive Care, Odense University Hospital

Odense, Denmark

Location

Roskilde Hospital

Roskilde, Denmark

Location

Slagelse Hospital

Slagelse, Denmark

Location

Viborg Hospital

Viborg, Denmark

Location

Related Publications (2)

• Munch MW, Granholm A, Kjaer MN, Aksnes TS, Solling CG, Christensen S, Perner A. Long-term mortality and health-related quality of life in the COVID STEROID trial. Acta Anaesthesiol Scand. 2022 Apr;66(4):543-545. doi: 10.1111/aas.14029. Epub 2022 Feb 3. No abstract available.

  PMID: 35067914 DERIVED

• Munch MW, Meyhoff TS, Helleberg M, Kjaer MN, Granholm A, Hjortso CJS, Jensen TS, Moller MH, Hjortrup PB, Wetterslev M, Vesterlund GK, Russell L, Jorgensen VL, Kristiansen KT, Benfield T, Ulrik CS, Andreasen AS, Bestle MH, Poulsen LM, Hildebrandt T, Knudsen LS, Moller A, Solling CG, Brochner AC, Rasmussen BS, Nielsen H, Christensen S, Strom T, Cronhjort M, Wahlin RR, Jakob SM, Cioccari L, Venkatesh B, Hammond N, Jha V, Myatra SN, Jensen MQ, Leistner JW, Mikkelsen VS, Svenningsen JS, Laursen SB, Hatley EV, Kristensen CM, Al-Alak A, Clapp E, Jonassen TB, Bjerregaard CL, Osterby NCH, Jespersen MM, Abou-Kassem D, Lassen ML, Zaabalawi R, Daoud MM, Abdi S, Meier N, la Cour K, Derby CB, Damlund BR, Laigaard J, Andersen LL, Mikkelsen J, Jensen JLS, Rasmussen AH, Arnerlov E, Lykke M, Holst-Hansen MZB, Tostesen BW, Schwab J, Madsen EK, Gluud C, Lange T, Perner A. Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: The COVID STEROID randomised, placebo-controlled trial. Acta Anaesthesiol Scand. 2021 Nov;65(10):1421-1430. doi: 10.1111/aas.13941. Epub 2021 Sep 20.

  PMID: 34138478 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

COVID-19; Hypoxia

Interventions

Hydrocortisone; hydrocortisone hemisuccinate; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Anders Perner, MD, PhD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2020
• First Posted: April 16, 2020
• Study Start: April 17, 2020
• Primary Completion: September 10, 2020
• Study Completion: September 8, 2021
• Last Updated: September 21, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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

Locations

DK (14)