Official Title
Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS
Brief 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. 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.

Active, not recruiting
Acute Hypoxemic Respiratory Failure
COVID-19

Drug: Dexamethasone injection
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.
CPAP 2
HFNO 2
Standard oxygen 2
mechanically ventilated 2
Other Name: experimental treatment

Drug: placebo
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.
CPAP 1
HFNO 1
Standard oxygen 1
mechanically ventilated 1

Procedure: conventional oxygen
The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)
Standard oxygen 1
Standard oxygen 2

Procedure: CPAP
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)
CPAP 1
CPAP 2

Procedure: HFNO
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
HFNO 1
HFNO 2

Procedure: mechanical ventilation
The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)
mechanically ventilated 1
mechanically ventilated 2

Eligibility Criteria

Inclusion Criteria: 1. Age ≥ 18 years 2. Admitted to ICU within 48 hours 3. Confirmed or highly suspected COVID-19 infection 4. Acute hypoxemic respiratory failure (PaO2 =6L/min) 5. 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: 1. Moribund status 2. Pregnancy or breastfeeding 3. Long term corticotherapy at a dose of 0.5mg/kg/j or higher 4. Active and untreated bacterial, fungal or parasitic infection 5. 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 6. hypersensitivity to dexamethasone or to any of the excipients 7. Not Affiliation to the French social security

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years
Countries
France

Jean François TIMSIT, Pr
Principal Investigator
Assistance Publique - Hôpitaux de Paris

Assistance Publique - Hôpitaux de Paris
NCT Number
Keywords
Covid-19
acute hypoxemic respiratory failure (AHRF)
MeSH Terms
Pneumonia
Respiratory Insufficiency
Dexamethasone
Dexamethasone acetate