Covid-19Phase 3COVID STEROIDNCT04348305
Hydrocortisone for COVID-19 and Severe Hypoxia
A Phase 3 study testing Hydrocortisone and Sodium Chloride 9mg/mL in people with Covid-19 and Hypoxia, run by Scandinavian Critical Care Trials Group at 14 sites in Denmark.
Trial summary
We aim to assess the benefits and harms of low-dose hydrocortisone in patients with COVID-19 and severe hypoxia. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Hydrocortisone and Sodium Chloride 9mg/mL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 14 sitesDenmark
- Study dates
- 17 Apr 2020to 8 Sep 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Denmark14 sites
Aarhus University Hospital - Dept of Intensive care
Aarhus
Rigshospitalet
Copenhagen, DK-2100
Dept of Infectious diseases, Rigshospitalet
Copenhagen
Herlev Hospital - Dept. of Intensive Care
Herlev
North Zealand Hospital
Hillerød
Hvidovre Hospital - Dept of Infectious diseases
Hvidovre
Hvidovre Hospital - Dept of Intensive Care
Hvidovre
Hvidovre Hospital - Dept of Pulmonary Medicine
Hvidovre
Køge Hospital
Køge
Kolding Hospital
Kolding
Dept of Intensive Care, Odense University Hospital
Odense
Roskilde Hospital
Roskilde
Slagelse Hospital
Slagelse
Viborg Hospital
Viborg
About this study
Official title: Low-dose Hydrocortisone in Patients With COVID-19 and Severe Hypoxia - the COVID STEROID Trial
We aim to assess the benefits and harms of low-dose hydrocortisone in patients with COVID-19 and severe hypoxia.
Read the 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%.
- Being tested
- Hydrocortisone, Sodium Chloride 9mg/mL
- Medical subject headings
- COVID-19, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Also called Solu-cortef
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/mLDrug
Also called Isotonic saline
Continuous infusion: 104 ml every 24 hours, Bolus injections: 10 ml every 6 hours, Total treatment duration: 7 days
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Sodium Chloride 9mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 28 after randomisation
Secondary outcomes (8)
All-cause mortality at day 28
Death from all causes
Measured: Day 28 after randomisation
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
Measured: Day 90 after randomisation
All-cause mortality at day 90
Death from all causes
Measured: Day 90 after randomisation
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
Measured: Day 14 after randomisation
Days alive and out of hospital at day 90
Number of days alive and out of hospital not limited to the index admission
Measured: Day 90 after randomisation
All-cause mortality at 1 year after randomisation
Death from all causes
Measured: 1 year after randomisation
Health-related quality of life at 1 year
Assessed by EQ-5D-5L
Measured: 1 year after randomisation
Health-related quality of life at 1 year
Assessed by EQ-VAS
Measured: 1 year after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2020
- Study start17 Apr 2020
- Primary completion10 Sep 2020
- Study completion8 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Covid-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scandinavian Critical Care Trials Group
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Copenhagen Trial Unit, Center for Clinical Intervention Research, University of Copenhagen, Aarhus University Hospital
- Responsible party
- Sponsor
- Investigators
- Anders Perner, MD, PhD, Study chair, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04348305
- Sponsor's protocol ID
- RH-ITA-008
- Other IDs
- 2020-001395-15
- Acronym
- COVID STEROID
- Status last verified
- Sep 2021
- First submitted
- 11 Apr 2020
- Last updated
- 21 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Fully de-identified IPD will be shared after the approval by the the trial management committee
Publications
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.
PubMed 35067914Munch 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.
PubMed 34138478
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-dose Hydrocortisone in Patients With COVID-19 and Severe Hypoxia - the COVID STEROID Trial
- ClinicalTrials.gov ID
- NCT04348305
- Acronym / sponsor ID
- COVID STEROID / RH-ITA-008
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Scandinavian Critical Care Trials GroupUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Copenhagen Trial Unit, Center for Clinical Intervention Research, University of Copenhagen, Aarhus University Hospital
- Study start
- 17 Apr 2020 (actual)
- Primary completion
- 10 Sep 2020 (actual)
- Study completion
- 8 Sep 2021 (actual)
- First posted
- 16 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We aim to assess the benefits and harms of low-dose hydrocortisone in patients with COVID-19 and severe hypoxia.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydrocortisone | Experimental | Drug: HydrocortisoneContinuous 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). |
| Isotonic Saline | Placebo comparator | Drug: Sodium Chloride 9mg/mLContinuous 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 18 years or above AND
- Confirmed SARS-CoV-2 (COVID-19) requiring hospitalisation AND
- Use of one of the following:
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisoneAlso: Solu-cortefContinuous infusion: 200 mg (104 ml) every 24 hours, Bolus injections: 50 mg (10 ml) every 6 hours, Total treatment duration: 7 days | Drug | Hydrocortisone |
| Sodium Chloride 9mg/mLAlso: Isotonic salineContinuous infusion: 104 ml every 24 hours, Bolus injections: 10 ml every 6 hours, Total treatment duration: 7 days | Drug | Isotonic Saline |
Primary outcome
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
8 secondary outcomes
All-cause mortality at day 28
Time frame: Day 28 after randomisation
Days alive without life support at day 90
Time frame: Day 90 after randomisation
All-cause mortality at day 90
Time frame: Day 90 after randomisation
Number of participants with one or more serious adverse reactions
Time frame: Day 14 after randomisation
Days alive and out of hospital at day 90
Time frame: Day 90 after randomisation
All-cause mortality at 1 year after randomisation
Time frame: 1 year after randomisation
Health-related quality of life at 1 year
Time frame: 1 year after randomisation
Health-related quality of life at 1 year
Time frame: 1 year after randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2021.
- Derived from this study: PubMed 35067914Munch 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.
- Derived from this study: PubMed 34138478Munch 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Fully de-identified IPD will be shared after the approval by the the trial management committee
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders Perner, MD, PhD study chair
Copenhagen University Hospital, Rigshospitalet
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydrocortisone and Sodium Chloride 9mg/mL in people with Covid-19 and Hypoxia, run by Scandinavian Critical Care Trials Group at 14 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days alive without life support at day 28 (time frame: Day 28 after randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04348305, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2021.