Clinical trial NCT04344730: Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 Pneumonia
Official title: Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Hypoxemic Respiratory Failure
COVID-19
Keywords: COVID-19
acute hypoxemic respiratory failure (AHRF)
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.
Primary purpose: TREATMENT

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.

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 \<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

Primary outcomes:
measure: The time-to-death from all causes
timeFrame: day-60
measure: The time to need for mechanical ventilation (MV)
timeFrame: day-28.
Secondary outcomes:
measure: The viral load in the respiratory tract
timeFrame: day-10
measure: Number of patient with at least one episode of healthcare-associated infections
timeFrame: day-28
measure: Number of days alive without mechanical ventilation
timeFrame: day-28
measure: Measure of SOFA score
timeFrame: day-1 to day 3, day 7, day 10, day 21, day 28
measure: Number of days alive without renal replacement therapy
timeFrame: day-28
measure: Lengths of ICU-stay
timeFrame: day-60
measure: Lengths of hospital-stay
timeFrame: day-60
measure: Number of patients with severe hypoxemia,
timeFrame: day 60
measure: Proportion of patients with cardiac arrest within 1 hour after intubation
timeFrame: day 60
measure: Overall survival
timeFrame: day 60
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Bichat - Aphp
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean François TIMSIT, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bouadma 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.