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

Not Applicable

• Conditions: Acute Hypoxemic Respiratory Failure; COVID-19
• Interventions: Drug: placebo; Drug: Dexamethasone injection; Procedure: conventional oxygen; Procedure: CPAP; Procedure: mechanical ventilation; Procedure: HFNO

• Registration Number: NCT04344730
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-04-09
• Study Start: 2020-04-10
• Study First Submitted QC: 2020-04-13
• Study First Posted: 2020-04-14
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-06
• Last Update Posted: 2021-02-09
• Primary Completion: 2021-12-31
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 550

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Standard oxygen 1	placebo	Standard oxygen and placebo of Dexamethasone
Standard oxygen 1	conventional oxygen	Standard oxygen and placebo of Dexamethasone
Standard oxygen 2	Dexamethasone injection	Standard oxygen and Dexamethasone
Standard oxygen 2	conventional oxygen	Standard oxygen and Dexamethasone
CPAP 1	placebo	CPAP and placebo of Dexamethasone
CPAP 1	CPAP	CPAP and placebo of Dexamethasone
mechanically ventilated 2	mechanical ventilation	Dexamethasone
CPAP 2	Dexamethasone injection	CPAP and Dexamethasone
CPAP 2	CPAP	CPAP and Dexamethasone
HFNO 1	placebo	HFNO and placebo of Dexamethasone
HFNO 1	HFNO	HFNO and placebo of Dexamethasone
HFNO 2	Dexamethasone injection	HFNO and Dexamethasone
mechanically ventilated 2	Dexamethasone injection	Dexamethasone
HFNO 2	HFNO	HFNO and Dexamethasone
mechanically ventilated 1	placebo	placebo
mechanically ventilated 1	mechanical ventilation	placebo

Primary Outcome Measures

Name	Time	Method
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.
The time-to-death from all causes	day-60	The time-to-death from all causes within the first 60 days after randomization.

Secondary Outcome Measures

Name	Time	Method
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)
Lengths of hospital-stay	day-60	To compare the lengths of hospital-stay
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
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

Trial Locations

Locations (1)

Hopital Bichat - Aphp; 🇫🇷 Paris, France