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Trial record 1 of 1 for:    NCT04344730
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Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 Pneumonia (COVIDICUS)

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ClinicalTrials.gov Identifier: NCT04344730
Recruitment Status : Recruiting
First Posted : April 14, 2020
Last Update Posted : April 14, 2020
Sponsor:
Information provided by (Responsible Party):
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.


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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
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 : April 10, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


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 Name: 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 Name: 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 Name: 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 Name: 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)




Primary Outcome Measures :
  1. The time-to-death from all causes [ Time Frame: day-60 ]
    The time-to-death from all causes within the first 60 days after randomization.

  2. The time to need for mechanical ventilation (MV) [ Time Frame: 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 :
  1. The viral load in the respiratory tract [ Time Frame: day-10 ]
    The cycle threshold for SARS-CoV-2 PCR at baseline, day 7 and day 10 in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)

  2. Number of patient with at least one episode of healthcare-associated infections [ Time Frame: day-28 ]
    Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28

  3. Number of days alive without mechanical ventilation [ Time Frame: day-28 ]
    To compare the exposition to mechanical ventilation

  4. Measure of SOFA score [ Time Frame: day-28 ]
    Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)

  5. Number of days alive without renal replacement therapy [ Time Frame: day-28 ]
    to compare the exposition to renal replacement therapy

  6. Lengths of ICU-stay [ Time Frame: day-60 ]
    To compare the lengths of ICU

  7. Lengths of hospital-stay [ Time Frame: day-60 ]
    To compare the lengths of hospital-stay

  8. Number of patients with severe hypoxemia, [ Time Frame: 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

  9. Number of patients with cardiac arrest within 1 hour after intubation [ Time Frame: day 60 ]
    Proportion of patients with cardiac arrest within 1 hour after intubation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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).

Exclusion 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
  6. hypersensitivity to dexamethasone or to any of the excipients
  7. Not Affiliation to the French social security

    In the subset of non-mechanically ventilated patients, additional non-inclusion criteria are:

  8. Anatomical factors precluding the use of nasal cannula
  9. Hypercapnia indicating NIV (paCO2 ≥ 50 mmHg)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04344730


Contacts
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Contact: Jean François TIMSIT, Pr 1 40 25 77 03 ext 33 jean-françois.timsit@aphp.fr
Contact: Lila Bouadma, Pr 1 40 25 77 03 ext 33 lila.bouadma@aphp.fr

Locations
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France
Hopital Bichat - Aphp Recruiting
Paris, France, 75018
Contact: LILA BOUADMA, Pr         
Contact: Jean-François TIMSIT, Pr         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Jean François TIMSIT, Pr Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04344730    
Other Study ID Numbers: APHP200388
2020-001457-43 ( EudraCT Number )
First Posted: April 14, 2020    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
COVID-19
acute hypoxemic respiratory failure (AHRF)
Additional relevant MeSH terms:
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Pneumonia
Respiratory Insufficiency
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Respiration Disorders
Dexamethasone
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents