Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 Pneumonia (COVIDICUS)

Assistance Publique - Hôpitaux de Paris

Status: Unknown

Conditions: COVID-19; Acute Hypoxemic Respiratory Failure

Treatments: Procedure: CPAP; Drug: Dexamethasone injection; Drug: placebo; Procedure: HFNO; Procedure: conventional oxygen; Procedure: mechanical ventilation

Study type: Interventional

Funder types: Other

Identifiers

NCT04344730

APHP200388

2020-001457-43 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 550 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 <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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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550 participants in 8 patient groups, including a placebo group

Standard oxygen 1

Placebo Comparator group

Description:

Standard oxygen and placebo of Dexamethasone

Treatment:

Drug: placebo

Procedure: conventional oxygen

Standard oxygen 2

Experimental group

Description:

Standard oxygen and Dexamethasone

Treatment:

Drug: Dexamethasone injection

Procedure: conventional oxygen

CPAP 1

Experimental group

Description:

CPAP and placebo of Dexamethasone

Treatment:

Procedure: CPAP

Drug: placebo

CPAP 2

Experimental group

Description:

CPAP and Dexamethasone

Treatment:

Procedure: CPAP

Drug: Dexamethasone injection

HFNO 1

Experimental group

Description:

HFNO and placebo of Dexamethasone

Treatment:

Drug: placebo

Procedure: HFNO

HFNO 2

Experimental group

Description:

HFNO and Dexamethasone

Treatment:

Drug: Dexamethasone injection

Procedure: HFNO

mechanically ventilated 1

Placebo Comparator group

Description:

placebo

Treatment:

Procedure: mechanical ventilation

Drug: placebo

mechanically ventilated 2

Experimental group

Description:

Dexamethasone

Treatment:

Procedure: mechanical ventilation

Drug: Dexamethasone injection