Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia (CORTICOVIDHUGO)
Primary Purpose
COVID-19
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Prednisone
Hydrocortisone
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- Adult patients ≥ 18 years old,
- Hospitalized with a proven diagnosis of COVID-19 (SARS-CoV-2 positive in RTPCR), in medicine or in intensive care.
- With a need for oxygen therapy ≥ 2 l / min to maintain a Sp02> 92% or a need for oxygen therapy to maintain a PaO2 / FiO2> 300 mmHg (for intubated patients).
- With a chest scanner at least 7 days after the onset of symptoms, and whose centralized interpretation shows a CT scan aspect suggestive of intense and predominant DAD which can explain the patient's oxygen dependence.
- Signature of a free, written and informed consent by the patient, or the person of trust
- Affiliate or beneficiary of a social security scheme.
Exclusion Criteria:
- Patients already treated by CS for a chronic disease.
- Patients with a known contraindication to SC, such as hypersensitivity.
- Patients at risk of dying within 48 hours.
- Pregnant or breastfeeding women.
- Patients under guardianship, curatorship, safeguard of justice.
- Poor understanding of the French language.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
corticosteroid + Optimized Standard of Care
Optimized Standard of Care
Arm Description
prednisone 0.7 mg/kg/day for 10 days, administered orally, once a day, or hydrocortisone hemisuccinate 3.5 mg/kg/day by continuous infusion for 10 days, administered by IV route if the patient cannot take drugs by oral route, standard of care
standard of care
Outcomes
Primary Outcome Measures
Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.
The 7-category ordinal scale is as follow:
Not hospitalized with resumption of usual activities
Not hospitalized, but unable to resume usual activities
Hospitalized, not requiring O2
Hospitalized, requiring O2 from 1 to 5 l/min
Hospitalized, requiring O2 >6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both
Hospitalized, requiring ECMO, invasive mechanical ventilation, or both
Death.
Secondary Outcome Measures
Proportion of patients free of oxygen at day 14 and 28
Proportion of patients discharged alive from hospital at day 14 and 28
Time to discharge for patients alive
Proportion of patients that were hospitalized to ICU or who died at day 14 and 28
14 and 28 day mortality rate
The time until weaning from oxygen therapy
The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28
Full Information
NCT ID
NCT04359511
First Posted
April 20, 2020
Last Updated
May 11, 2021
Sponsor
University Hospital, Tours
1. Study Identification
Unique Protocol Identification Number
NCT04359511
Brief Title
Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia
Acronym
CORTICOVIDHUGO
Official Title
Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia in Grand Ouest Interregion France
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Withdrawn
Why Stopped
COMPETITOR TEST (RECOVERY)
Study Start Date
July 3, 2020 (Actual)
Primary Completion Date
July 3, 2020 (Actual)
Study Completion Date
July 3, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD).
We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.
Detailed Description
"Severe acute respiratory syndrome" coronavirus 2 (SARS-Cov-2) is a new coronavirus that induces pneumonia called Corona Virus Disease- 19 (COVID-19), an infected 1.5 million people worldwide and caused the more than 85,000 patients died. COVID-19 usually comes in the form of viral pneumonia but with the peculiarities of a risk frequent worsening towards acute respiratory distress syndrome (ARDS) and a usual duration of oxygen dependence in fragile patients by their age or their comorbidities. To date, there is no therapy effective in preventing or treating COVID-19. Drug identification is a major concern and a public health emergency. Retrospective study (Wu 2020) highlighted improved survival in COVID-19 patients with acute ARDS and treated with corticosteroids (CS). So even in the absence of evidence of effectiveness, the SCs are used for COVID-19 oxygen-dependent patients or with an ARDS. However, their benefit / risk remains debated (Russel 2020). On histological samples of COVID-19, diffuse alveolar damage (DAD) has been especially observed (Hanley 2020). DAD is described histologically in an exudative phase, an organizational phase and a irreversible fibrotic phase (Hughes 2017). SC could have an effect beneficial by limiting the exudative / inflammatory phase but also that organization whose histological and CT aspects are sometimes indistinguishable from organized pneumonia, a form of pulmonary repair aberrant very corticosensitive (Travis 2013). Chest scans performed in the face of the persistence or worsening of oxygen dependence beyond the 7th day of COVID-19 symptoms, could help discern indirect complications (pulmonary embolism, exacerbation of COPD, bacterial superinfection, etc.) of an unfavorable course COVID-19 (by displaying an aspect suggesting DAD in particular during the organization phase). We hypothesize that, in the context of COVID-19, the SCs may be beneficial in patients with CT scans thoracic images suggestive of DAD either at the exudative phase or at the pulmonary organization phase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
corticosteroid + Optimized Standard of Care
Arm Type
Experimental
Arm Description
prednisone 0.7 mg/kg/day for 10 days, administered orally, once a day, or
hydrocortisone hemisuccinate 3.5 mg/kg/day by continuous infusion for 10 days, administered by IV route if the patient cannot take drugs by oral route,
standard of care
Arm Title
Optimized Standard of Care
Arm Type
No Intervention
Arm Description
standard of care
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
prednisone 0.7 mg/kg/d (PO)
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
hémisuccinate d'hydrocortisone 3,5 mg/kg/jour (IV)
Primary Outcome Measure Information:
Title
Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.
Description
The 7-category ordinal scale is as follow:
Not hospitalized with resumption of usual activities
Not hospitalized, but unable to resume usual activities
Hospitalized, not requiring O2
Hospitalized, requiring O2 from 1 to 5 l/min
Hospitalized, requiring O2 >6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both
Hospitalized, requiring ECMO, invasive mechanical ventilation, or both
Death.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Proportion of patients free of oxygen at day 14 and 28
Time Frame
14 and 28 days
Title
Proportion of patients discharged alive from hospital at day 14 and 28
Time Frame
14 and 28 days
Title
Time to discharge for patients alive
Time Frame
28 days
Title
Proportion of patients that were hospitalized to ICU or who died at day 14 and 28
Time Frame
14 and 28 days
Title
14 and 28 day mortality rate
Time Frame
14 and 28 days
Title
The time until weaning from oxygen therapy
Time Frame
28 days
Title
The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28
Time Frame
14 and 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients ≥ 18 years old,
Hospitalized with a proven diagnosis of COVID-19 (SARS-CoV-2 positive in RTPCR), in medicine or in intensive care.
With a need for oxygen therapy ≥ 2 l / min to maintain a Sp02> 92% or a need for oxygen therapy to maintain a PaO2 / FiO2> 300 mmHg (for intubated patients).
With a chest scanner at least 7 days after the onset of symptoms, and whose centralized interpretation shows a CT scan aspect suggestive of intense and predominant DAD which can explain the patient's oxygen dependence.
Signature of a free, written and informed consent by the patient, or the person of trust
Affiliate or beneficiary of a social security scheme.
Exclusion Criteria:
Patients already treated by CS for a chronic disease.
Patients with a known contraindication to SC, such as hypersensitivity.
Patients at risk of dying within 48 hours.
Pregnant or breastfeeding women.
Patients under guardianship, curatorship, safeguard of justice.
Poor understanding of the French language.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
LOUIS BERNARD, MD, PhD
Organizational Affiliation
CHRU DE TOURS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
JOUNEAU STEPHANE, MD, PhD
Organizational Affiliation
Rennes University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
MAILLOT FRANCOIS, MD
Organizational Affiliation
CHRU DE TOURS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
LIOGER BERTRAND, MD
Organizational Affiliation
CH DE BLOIS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GOUPIL FRANCOIS, MD
Organizational Affiliation
CH Le Mans
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
RABUT Thi- Tuyet Hong, MD
Organizational Affiliation
CH DE CHARTRES
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
POPA Mihai, MD
Organizational Affiliation
CH DE RDREUX
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
MOREL HUGUES, MD
Organizational Affiliation
CHR ORLEANS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
GUY TIPHAINE, MD
Organizational Affiliation
CH DE VANNES
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
LEMMENS BRUNO, MD
Organizational Affiliation
CH AMBOISE
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
BAZIN YANN, MD
Organizational Affiliation
CH SAINT MALO
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
ROY XAVIER, MD
Organizational Affiliation
CH DE CHATEAUROUX
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
PECQUERIAUX OLIVIER, MD
Organizational Affiliation
CH DE BOURGES
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
MARCHAND ADAM Sylvain, MD, PhD
Organizational Affiliation
CHRU DE TOURS
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia
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