Acute Hypoxemic Respiratory FailureCOVIDICUSNCT04344730
Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 Pneumonia
A study testing Dexamethasone injection, conventional oxygen and CPAP in people with Acute Hypoxemic Respiratory Failure and COVID-19, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality. Two hypotheses will be tested in this study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, COVID-19
- What is being tested?
- Dexamethasone injection, conventional oxygen and CPAP
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 550 participants
- Where
- 1 siteFrance
- Study dates
- 10 Apr 2020to 31 Dec 2021
- Phase
- Interventional
- 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
- Age ≥ 18 years
- Admitted to ICU within 48 hours
- Confirmed or highly suspected COVID-19 infection
- Acute hypoxemic respiratory failure (PaO2 <70 mmHg or SpO2<90% on room air or tachypnea>30/min or labored breathing or respiratory distress; need for oxygen flow >=6L/min)
- Any treatment intended to treat the SARS-CoV-2 infection in the absence of contraindications (either as a compassionate use or in the context of a clinical trial, i.e remdesivir, lopinavir/ritonavir, favipiravir, hydroxychloroquine and any other new drug with potential activity).
- Non-inclusion Criteria:
Show all 13Show fewer
- Moribund status
- Pregnancy or breastfeeding
- Long term corticotherapy at a dose of 0.5mg/kg/j or higher
- Active and untreated bacterial, fungal or parasitic infection
- Not Written informed consent from the patient or a legal representative if appropriate . If absence a legal representative the patient may be included in emergency procedure
- hypersensitivity to dexamethasone or to any of the excipients
- Not Affiliation to the French social security
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality.
Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival.
The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
Read the detailed description
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality.
Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival.
The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
The main objective is to assess the impact of dexamethasone on overall mortality at day-60 after randomization in patients admitted in ICU for severe COVID-19 infection.
In non mechanical ventilation (MV) patients, the additional objective is to assess whether oxygen support based on either HFNO or CPAP modality in COVID-19 related AHRF reduces the need for mechanical ventilation at day-28.
An ancillary study CACAO (COVIDICUS air contamination) will be performed in 4 centers aiming at assessing the environmental contamination by SARS-CoV-2 according to the oxygen support modality. Additional funding will be searched for these analyses (submitted for ANR call).
A metanalysis on individual data will be performed using patients enrolled in the 3 PHRC flash exploring the activity of corticosteroids.
- Conditions
- Acute Hypoxemic Respiratory Failure, COVID-19
- Being tested
- Dexamethasone injection, placebo, conventional oxygen, CPAP, HFNO
- Keywords
- COVID-19, acute hypoxemic respiratory failure (AHRF)
- Medical subject headings
- Respiratory Insufficiency, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone injectionDrug
Also called experimental treatment
Box of 10 DEXAMETHASONE 20 mg / 5 ml, solution for injection in ampoule of 5mL. Each allocated box contains complete treatment from D1 to D10 for one patient.
placeboDrug
Box of 10 NaCl 0,9% , solution for injection in ampoule of 5mL. Each allocated box contains complete treatment from D1 to D10 for one patient.
conventional oxygenProcedure or surgery
The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)
CPAPProcedure or surgery
Patients assigned to the CPAP plus oxygen group will receive periods of CPAP in addition to the standard treatment.The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)
HFNOProcedure or surgery
TIn the high-flow-nasal cannula group, oxygen will be delivered through a heated humidifier (Airvo-2, Fisher and Paykel Healthcare) and applied continuously through large-bore binasal prongs, with a gas flow rate of 30 liters per minute and adjusted based on the clinical response. FiO2 will be adjusted for the target SpO2
mechanical ventilationProcedure or surgery
The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)
| Study group | Role | What they receive |
|---|---|---|
| Standard oxygen 1 | Placebo comparator | Standard oxygen and placebo of Dexamethasone Receives: Drug: placebo; Procedure: conventional oxygen |
| Standard oxygen 2 | Experimental | Standard oxygen and Dexamethasone Receives: Drug: Dexamethasone injection; Procedure: conventional oxygen |
| CPAP 1 | Experimental | CPAP and placebo of Dexamethasone Receives: Drug: placebo; Procedure: CPAP |
| CPAP 2 | Experimental | CPAP and Dexamethasone Receives: Drug: Dexamethasone injection; Procedure: CPAP |
| HFNO 1 | Experimental | HFNO and placebo of Dexamethasone Receives: Drug: placebo; Procedure: HFNO |
| HFNO 2 | Experimental | HFNO and Dexamethasone Receives: Drug: Dexamethasone injection; Procedure: HFNO |
| mechanically ventilated 1 | Placebo comparator | placebo Receives: Drug: placebo; Procedure: mechanical ventilation |
| mechanically ventilated 2 | Experimental | Dexamethasone Receives: Drug: Dexamethasone injection; Procedure: mechanical ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The time-to-death from all causes
The time-to-death from all causes within the first 60 days after randomization.
Measured: day-60
The time to need for mechanical ventilation (MV)
the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.
Measured: day-28.
Secondary outcomes (10)
The viral load in the respiratory tract
The cycle threshold for SARS-CoV-2 PCR at baseline, day 7+/-1 and day 10 +/- in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)
Measured: day-10
Number of patient with at least one episode of healthcare-associated infections
Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28
Measured: day-28
Number of days alive without mechanical ventilation
To compare the exposition to mechanical ventilation
Measured: day-28
Measure of SOFA score
Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)
Measured: day-1 to day 3, day 7, day 10, day 21, day 28
Number of days alive without renal replacement therapy
to compare the exposition to renal replacement therapy
Measured: day-28
Lengths of ICU-stay
To compare the lengths of ICU
Measured: day-60
Lengths of hospital-stay
To compare the lengths of hospital-stay
Measured: day-60
Number of patients with severe hypoxemia,
Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation
Measured: day 60
Proportion of patients with cardiac arrest within 1 hour after intubation
Proportion of patients with cardiac arrest within 1 hour after intubation
Measured: day 60
Overall survival
To compare Overall survival after randomization
Measured: day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2020
- Study start10 Apr 2020
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 550 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean François TIMSIT, Pr, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04344730
- Sponsor's protocol ID
- APHP200388
- Other IDs
- 2020-001457-43
- Acronym
- COVIDICUS
- Status last verified
- Feb 2021
- First submitted
- 9 Apr 2020
- Last updated
- 9 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chevret S, Bouadma L, Dupuis C, Burdet C, Timsit JF; COVIDICUS RCT group. Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial. Ann Intensive Care. 2023 Aug 27;13(1):75. doi: 10.1186/s13613-023-01168-z.
PubMed 37634234Chevret S, Timsit JF, Biard L. Challenges of using external data in clinical trials- an illustration in patients with COVID-19. BMC Med Res Methodol. 2022 Dec 15;22(1):321. doi: 10.1186/s12874-022-01769-5.
PubMed 36522698Bouadma L, Mekontso-Dessap A, Burdet C, Merdji H, Poissy J, Dupuis C, Guitton C, Schwebel C, Cohen Y, Bruel C, Marzouk M, Geri G, Cerf C, Megarbane B, Garcon P, Kipnis E, Visseaux B, Beldjoudi N, Chevret S, Timsit JF; COVIDICUS Study Group. High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure: The COVIDICUS Randomized Clinical Trial. JAMA Intern Med. 2022 Sep 1;182(9):906-916. doi: 10.1001/jamainternmed.2022.2168.
PubMed 35788622
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS
- ClinicalTrials.gov ID
- NCT04344730
- Acronym / sponsor ID
- COVIDICUS / APHP200388
- Conditions
- Acute Hypoxemic Respiratory Failure, COVID-19
- Keywords
- COVID-19, acute hypoxemic respiratory failure (AHRF)
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 550 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 10 Apr 2020 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 14 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.
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality.
Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival.
The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
Detailed description
The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality.
Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival.
The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.
The main objective is to assess the impact of dexamethasone on overall mortality at day-60 after randomization in patients admitted in ICU for severe COVID-19 infection.
In non mechanical ventilation (MV) patients, the additional objective is to assess whether oxygen support based on either HFNO or CPAP modality in COVID-19 related AHRF reduces the need for mechanical ventilation at day-28.
An ancillary study CACAO (COVIDICUS air contamination) will be performed in 4 centers aiming at assessing the environmental contamination by SARS-CoV-2 according to the oxygen support modality. Additional funding will be searched for these analyses (submitted for ANR call).
A metanalysis on individual data will be performed using patients enrolled in the 3 PHRC flash exploring the activity of corticosteroids.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
- Model description
- In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.
| Arm | Type | Receives |
|---|---|---|
| Standard oxygen 1 | Placebo comparator | Drug: placebo, Procedure: conventional oxygenStandard oxygen and placebo of Dexamethasone |
| Standard oxygen 2 | Experimental | Drug: Dexamethasone injection, Procedure: conventional oxygenStandard oxygen and Dexamethasone |
| CPAP 1 | Experimental | Drug: placebo, Procedure: CPAPCPAP and placebo of Dexamethasone |
| CPAP 2 | Experimental | Drug: Dexamethasone injection, Procedure: CPAPCPAP and Dexamethasone |
| HFNO 1 | Experimental | Drug: placebo, Procedure: HFNOHFNO and placebo of Dexamethasone |
| HFNO 2 | Experimental | Drug: Dexamethasone injection, Procedure: HFNOHFNO and Dexamethasone |
| mechanically ventilated 1 | Placebo comparator | Drug: placebo, Procedure: mechanical ventilationplacebo |
| mechanically ventilated 2 | Experimental | Drug: Dexamethasone injection, Procedure: mechanical ventilationDexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age ≥ 18 years
- Admitted to ICU within 48 hours
- Confirmed or highly suspected COVID-19 infection
- Acute hypoxemic respiratory failure (PaO2 <70 mmHg or SpO2<90% on room air or tachypnea>30/min or labored breathing or respiratory distress; need for oxygen flow >=6L/min)
- Any treatment intended to treat the SARS-CoV-2 infection in the absence of contraindications (either as a compassionate use or in the context of a clinical trial, i.e remdesivir, lopinavir/ritonavir, favipiravir, hydroxychloroquine and any other new drug with potential activity).
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Dexamethasone injectionAlso: experimental treatmentBox of 10 DEXAMETHASONE 20 mg / 5 ml, solution for injection in ampoule of 5mL. Each allocated box contains complete treatment from D1 to D10 for one patient. | Drug | CPAP 2, HFNO 2, Standard oxygen 2, mechanically ventilated 2 |
| placeboBox of 10 NaCl 0,9% , solution for injection in ampoule of 5mL. Each allocated box contains complete treatment from D1 to D10 for one patient. | Drug | CPAP 1, HFNO 1, Standard oxygen 1, mechanically ventilated 1 |
| conventional oxygenThe oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2) | Procedure or surgery | Standard oxygen 1, Standard oxygen 2 |
| CPAPPatients assigned to the CPAP plus oxygen group will receive periods of CPAP in addition to the standard treatment.The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2) | Procedure or surgery | CPAP 1, CPAP 2 |
| HFNOTIn the high-flow-nasal cannula group, oxygen will be delivered through a heated humidifier (Airvo-2, Fisher and Paykel Healthcare) and applied continuously through large-bore binasal prongs, with a gas flow rate of 30 liters per minute and adjusted based on the clinical response. FiO2 will be adjusted for the target SpO2 | Procedure or surgery | HFNO 1, HFNO 2 |
| mechanical ventilationThe oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2) | Procedure or surgery | mechanically ventilated 1, mechanically ventilated 2 |
Primary outcome
The time-to-death from all causes
Time frame: day-60
The time-to-death from all causes within the first 60 days after randomization.
The time to need for mechanical ventilation (MV)
Time frame: day-28.
the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.
10 secondary outcomes
The viral load in the respiratory tract
Time frame: day-10
Number of patient with at least one episode of healthcare-associated infections
Time frame: day-28
Number of days alive without mechanical ventilation
Time frame: day-28
Measure of SOFA score
Time frame: day-1 to day 3, day 7, day 10, day 21, day 28
Number of days alive without renal replacement therapy
Time frame: day-28
Lengths of ICU-stay
Time frame: day-60
Lengths of hospital-stay
Time frame: day-60
Number of patients with severe hypoxemia,
Time frame: day 60
Proportion of patients with cardiac arrest within 1 hour after intubation
Time frame: day 60
Overall survival
Time frame: day 60
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
- Derived from this study: PubMed 37634234Chevret S, Bouadma L, Dupuis C, Burdet C, Timsit JF; COVIDICUS RCT group. Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial. Ann Intensive Care. 2023 Aug 27;13(1):75. doi: 10.1186/s13613-023-01168-z.
- Derived from this study: PubMed 36522698Chevret S, Timsit JF, Biard L. Challenges of using external data in clinical trials- an illustration in patients with COVID-19. BMC Med Res Methodol. 2022 Dec 15;22(1):321. doi: 10.1186/s12874-022-01769-5.
- Derived from this study: PubMed 35788622Bouadma L, Mekontso-Dessap A, Burdet C, Merdji H, Poissy J, Dupuis C, Guitton C, Schwebel C, Cohen Y, Bruel C, Marzouk M, Geri G, Cerf C, Megarbane B, Garcon P, Kipnis E, Visseaux B, Beldjoudi N, Chevret S, Timsit JF; COVIDICUS Study Group. High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure: The COVIDICUS Randomized Clinical Trial. JAMA Intern Med. 2022 Sep 1;182(9):906-916. doi: 10.1001/jamainternmed.2022.2168.
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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.
Jean François TIMSIT, Pr principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexamethasone injection, conventional oxygen and CPAP in people with Acute Hypoxemic Respiratory Failure and COVID-19, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 13 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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.
Are results available for this study?
Results are not available in the source record.
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?
The time-to-death from all causes (time frame: day-60). The study lists 2 primary outcomes in all. 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 NCT04344730, which also lists 3 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 9 Feb 2021.