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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 : Active, not recruiting
First Posted : April 14, 2020
Last Update Posted : February 9, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE April 9, 2020
First Posted Date  ICMJE April 14, 2020
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE April 10, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2021)
  • The viral load in the respiratory tract [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: day-28 ]
    To compare the exposition to mechanical ventilation
  • Measure of SOFA score [ Time Frame: 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 [ Time Frame: day-28 ]
    to compare the exposition to renal replacement therapy
  • Lengths of ICU-stay [ Time Frame: day-60 ]
    To compare the lengths of ICU
  • Lengths of hospital-stay [ Time Frame: day-60 ]
    To compare the lengths of hospital-stay
  • 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
  • Proportion 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
  • Overall survival [ Time Frame: day 60 ]
    To compare Overall survival after randomization
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
  • 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)
  • 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
  • Number of days alive without mechanical ventilation [ Time Frame: day-28 ]
    To compare the exposition to mechanical ventilation
  • 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)
  • Number of days alive without renal replacement therapy [ Time Frame: day-28 ]
    to compare the exposition to renal replacement therapy
  • Lengths of ICU-stay [ Time Frame: day-60 ]
    To compare the lengths of ICU
  • Lengths of hospital-stay [ Time Frame: day-60 ]
    To compare the lengths of hospital-stay
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 Pneumonia
Official Title  ICMJE Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE
  • Acute Hypoxemic Respiratory Failure
  • COVID-19
Intervention  ICMJE
  • 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
  • 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)
  • 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)
  • 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
  • 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)
Study Arms  ICMJE
  • Placebo Comparator: Standard oxygen 1
    Standard oxygen and placebo of Dexamethasone
    Interventions:
    • Drug: placebo
    • Procedure: conventional oxygen
  • Experimental: Standard oxygen 2
    Standard oxygen and Dexamethasone
    Interventions:
    • Drug: Dexamethasone injection
    • Procedure: conventional oxygen
  • Experimental: CPAP 1
    CPAP and placebo of Dexamethasone
    Interventions:
    • Drug: placebo
    • Procedure: CPAP
  • Experimental: CPAP 2
    CPAP and Dexamethasone
    Interventions:
    • Drug: Dexamethasone injection
    • Procedure: CPAP
  • Experimental: HFNO 1
    HFNO and placebo of Dexamethasone
    Interventions:
    • Drug: placebo
    • Procedure: HFNO
  • Experimental: HFNO 2
    HFNO and Dexamethasone
    Interventions:
    • Drug: Dexamethasone injection
    • Procedure: HFNO
  • Placebo Comparator: mechanically ventilated 1
    placebo
    Interventions:
    • Drug: placebo
    • Procedure: mechanical ventilation
  • Experimental: mechanically ventilated 2
    Dexamethasone
    Interventions:
    • Drug: Dexamethasone injection
    • Procedure: mechanical ventilation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 13, 2020)
550
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04344730
Other Study ID Numbers  ICMJE APHP200388
2020-001457-43 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jean François TIMSIT, Pr Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP