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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04344730

Collaborator

(none)

550

Enrollment

Location

Arms

20.7

Anticipated Duration (Months)

26.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Hypoxemic Respiratory Failure COVID-19	Drug: Dexamethasone injection Drug: placebo Procedure: conventional oxygen Procedure: CPAP Procedure: HFNO Procedure: mechanical ventilation	N/A

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 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

Study Type:

Interventional

Actual Enrollment :

550 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.In non-mechanically ventilated patients, a 2x2 factorial design will be used to assess the two interventions, separately.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The masking label is available only for the treatment assignation

Primary Purpose:

Treatment

Official Title:

Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS

Actual Study Start Date :

Apr 10, 2020

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Standard oxygen 1 Standard oxygen and placebo of Dexamethasone	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)
Experimental: Standard oxygen 2 Standard oxygen and Dexamethasone	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 Names: experimental treatment 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)
Experimental: CPAP 1 CPAP and placebo of Dexamethasone	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: 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)
Experimental: CPAP 2 CPAP and Dexamethasone	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 Names: experimental treatment 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)
Experimental: HFNO 1 HFNO and placebo of Dexamethasone	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: 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
Experimental: HFNO 2 HFNO and Dexamethasone	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 Names: experimental treatment 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
Placebo Comparator: mechanically ventilated 1 placebo	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: 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)
Experimental: mechanically ventilated 2 Dexamethasone	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 Names: experimental treatment 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)

Outcome Measures

Primary Outcome Measures

The time-to-death from all causes [day-60]
The time-to-death from all causes within the first 60 days after randomization.
The time to need for mechanical ventilation (MV) [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.

Secondary Outcome Measures

The viral load in the respiratory tract [day-10]
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)
Number of patient with at least one episode of healthcare-associated infections [day-28]
Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28
Number of days alive without mechanical ventilation [day-28]
To compare the exposition to mechanical ventilation
Measure of SOFA score [day-1 to day 3, day 7, day 10, day 21, day 28]
Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)
Number of days alive without renal replacement therapy [day-28]
to compare the exposition to renal replacement therapy
Lengths of ICU-stay [day-60]
To compare the lengths of ICU
Lengths of hospital-stay [day-60]
To compare the lengths of hospital-stay
Number of patients with severe hypoxemia, [day 60]
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
Proportion of patients with cardiac arrest within 1 hour after intubation [day 60]
Proportion of patients with cardiac arrest within 1 hour after intubation
Overall survival [day 60]
To compare Overall survival after randomization

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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:

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