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 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.
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.
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.
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)
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)
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
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)
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 <70 mmHg or SpO2<90% on room air or
tachypnea>30/min or labored breathing or respiratory distress; need for oxygen flow
>=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
Hopital Bichat - Aphp
Paris, France
Jean François TIMSIT, Pr, Principal Investigator
Assistance Publique - Hôpitaux de Paris