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

NCT ID: NCT04344730

Last Updated: 2021-02-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

550 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-10

Study Completion Date

2021-12-31

Brief Summary

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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

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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.

Conditions

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Acute Hypoxemic Respiratory Failure COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

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

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The masking label is available only for the treatment assignation

Study Groups

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Standard oxygen 1

Standard oxygen and placebo of Dexamethasone

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

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.

conventional oxygen

Intervention Type PROCEDURE

The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)

Standard oxygen 2

Standard oxygen and Dexamethasone

Group Type EXPERIMENTAL

Dexamethasone injection

Intervention Type DRUG

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.

conventional oxygen

Intervention Type PROCEDURE

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 1

CPAP and placebo of Dexamethasone

Group Type EXPERIMENTAL

placebo

Intervention Type DRUG

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.

CPAP

Intervention Type PROCEDURE

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)

CPAP 2

CPAP and Dexamethasone

Group Type EXPERIMENTAL

Dexamethasone injection

Intervention Type DRUG

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.

CPAP

Intervention Type PROCEDURE

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 1

HFNO and placebo of Dexamethasone

Group Type EXPERIMENTAL

placebo

Intervention Type DRUG

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.

HFNO

Intervention Type PROCEDURE

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

HFNO 2

HFNO and Dexamethasone

Group Type EXPERIMENTAL

Dexamethasone injection

Intervention Type DRUG

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.

HFNO

Intervention Type PROCEDURE

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

mechanically ventilated 1

placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

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.

mechanical ventilation

Intervention Type PROCEDURE

The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)

mechanically ventilated 2

Dexamethasone

Group Type EXPERIMENTAL

Dexamethasone injection

Intervention Type DRUG

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.

mechanical ventilation

Intervention Type PROCEDURE

The oxygen flow will be adjusted to maintain an oxygen saturation level of 92% or more, as measured by means of pulse oximetry (SpO2)

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

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)

Intervention Type 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)

Intervention Type 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

Intervention Type 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)

Intervention Type PROCEDURE

Other Intervention Names

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experimental treatment

Eligibility Criteria

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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).


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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean François TIMSIT, Pr

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Hopital Bichat - Aphp

Paris, , France

Site Status

Countries

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France

References

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Chevret S, Bouadma L, Dupuis C, Burdet C, Timsit JF; COVIDICUS RCT group. Which severe COVID-19 patients could benefit from high dose dexamethasone? A Bayesian post-hoc reanalysis of the COVIDICUS randomized clinical trial. Ann Intensive Care. 2023 Aug 27;13(1):75. doi: 10.1186/s13613-023-01168-z.

Reference Type DERIVED
PMID: 37634234 (View on PubMed)

Chevret S, Timsit JF, Biard L. Challenges of using external data in clinical trials- an illustration in patients with COVID-19. BMC Med Res Methodol. 2022 Dec 15;22(1):321. doi: 10.1186/s12874-022-01769-5.

Reference Type DERIVED
PMID: 36522698 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35788622 (View on PubMed)

Other Identifiers

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2020-001457-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP200388

Identifier Type: -

Identifier Source: org_study_id

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