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

COVID-19 Clinical Trial

— COVIDICUS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04344730
• Other study ID #: APHP200388
• Secondary ID: 2020-001457-43
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 10, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 550
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Hypoxemic Respiratory Failure
• COVID-19
• Pneumonia
• Respiratory Insufficiency

Intervention

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.
• 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)
• 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)
• 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
• 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)

Locations

Country	Name	City	State
France	Hopital Bichat - Aphp	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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