Back to resultsStudy of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial - CORIMUNO-19 - VIRO (CORIMUNO-VIRO)
Primary Purpose
COVID19, SARS-CoV-2 Infection
Status
Suspended
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Sarilumab
Azithromycin
Hydroxychloroquine
Sponsored by
About this trial
This is an interventional treatment trial for COVID19
Eligibility Criteria
Inclusion Criteria:
- Patients included in the CORIMUNO-19 cohort (NCT04324047)
COVID-19 cases not requiring ICU at admission with moderate or severe pneumopathy according to the WHO Criteria of severity of COVID pneumopathy:
- Moderate cases: Cases meeting all of the following criteria: [Showing fever and respiratory symptoms with radiological findings of pneumonia] AND [Requiring between 3L/min and 5L/min of oxygen to maintain SpO2>97%] OR
- Severe cases: Cases meeting any of the following criteria: [Respiratory distress ( ≥ 30 breaths/ min)] OR [Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 > 5L/min] OR [PaO2/FiO2 ≤ 300mmHg]
Exclusion Criteria:
- Patients with exclusion criteria to the CORIMUNO-19 cohort.
- Respiratory failure requiring non invasive or mechanical ventilation
- Patients requiring intensive care
- Do-not-resuscitate order (DNR order)
- Known hypersensitivity to sarilumab or to any of their excipients.
- Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation
- Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation
- Pregnancy or breastfeeding
- Current documented bacterial infection.
Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
- Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
- Haemoglobin level: no limitation
- Platelets (PLT) < 50 G /L
- SGOT or SGPT > 5N
Sites / Locations
- AP-HP Hôpital Avicenne
- AP-HP Hôpital Ambroise Paré
- AP-HP Hôpital Beaujon
- AP-HP Hôpital Pitié Salpétrière
- AP-HP Hôpital Saint Antoine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sarilumab + Azithromycin + Hydroxychloroquine
Sarilumab
Arm Description
Sarilumab combined with Azithromycin and Hydroxychloroquine
Sarilumab only
Outcomes
Primary Outcome Measures
Need for ventilation (including invasive and non invasive ventilation), intensive care or death
Events considered are: need for ventilation (including invasive and non invasive ventilation), transfer to the Intensive Care Unit, death or new do-not-resuscitate (DNR) decision in the absence ventilation and outside ICU.
Secondary Outcome Measures
Early improvement: OMS progression scale <= 5
WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
OMS progression scale
WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Survival
Overall survival
ICU-free days alive
Number of ICU-free days alive
Ventilation-free days alive
Number of ventilation(invasive or non invasive)-free days alive
Hospital-free days alive
Number of hospital-free days alive
Oxygen therapy-free days alive
Number of oxygen therapy-free days alive
Time to negative viral excretion
SARS-CoV-2 viral load measurement by rtPCR
Immunophenotyping and multiplex cytokines
Immunophenotyping and multiplex cytokines (blood sample)
Full Information
NCT ID
NCT04341870
First Posted
April 6, 2020
Last Updated
May 4, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04341870
Brief Title
Study of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial - CORIMUNO-19 - VIRO
Acronym
CORIMUNO-VIRO
Official Title
Efficacy of Sarilumab + Azithromycin + Hydroxychloroquine, and Sarilumab Alone, for Adult Patients Hospitalized With Moderate to Severe COVID-19: a Multicenter Open-label 1:1 Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Suspended
Why Stopped
DSMB recommendation (futility)
Study Start Date
April 11, 2020 (Actual)
Primary Completion Date
May 8, 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in combination with Azithromycin and Hydroxychloroquine, compared to Sarilumab only, patients with moderate, severe pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering investigational treatments administration to patients enrolled in the CORIMUNO-19 cohort (NCT04324047). Sarilumab+Azithromycin+Hydroxychloroquine, or Sarilumab only will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation. All patients will receive standard of care along with randomized investigational treatments. Outcomes of included patients will be compared between groups as well as with outcomes of patients in the CORIMUNO-19 cohort treated with other immune modulators or standard of care.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19, SARS-CoV-2 Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Bayesian open labelled randomized clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sarilumab + Azithromycin + Hydroxychloroquine
Arm Type
Experimental
Arm Description
Sarilumab combined with Azithromycin and Hydroxychloroquine
Arm Title
Sarilumab
Arm Type
Active Comparator
Arm Description
Sarilumab only
Intervention Type
Drug
Intervention Name(s)
Sarilumab
Intervention Description
Sarilumab: 400 mg in a 1 hour - I.V. infusion on D1
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
Azithromycin: oral administration, 500mg on D1 then 250mg QD on D2 to D5 (total duration 5 days)
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine: oral administration, 600mg QD (200mg TID) from D1 to D10 (total duration 10 days)
Primary Outcome Measure Information:
Title
Need for ventilation (including invasive and non invasive ventilation), intensive care or death
Description
Events considered are: need for ventilation (including invasive and non invasive ventilation), transfer to the Intensive Care Unit, death or new do-not-resuscitate (DNR) decision in the absence ventilation and outside ICU.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Early improvement: OMS progression scale <= 5
Description
WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Time Frame
4 days
Title
OMS progression scale
Description
WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Time Frame
4, 7 and 14 days
Title
Survival
Description
Overall survival
Time Frame
14, 28 and 90 days
Title
ICU-free days alive
Description
Number of ICU-free days alive
Time Frame
14, 28 and 90 days
Title
Ventilation-free days alive
Description
Number of ventilation(invasive or non invasive)-free days alive
Time Frame
14 and 28 days
Title
Hospital-free days alive
Description
Number of hospital-free days alive
Time Frame
14, 28 and 90 days
Title
Oxygen therapy-free days alive
Description
Number of oxygen therapy-free days alive
Time Frame
14 and 28 days
Title
Time to negative viral excretion
Description
SARS-CoV-2 viral load measurement by rtPCR
Time Frame
90 days
Title
Immunophenotyping and multiplex cytokines
Description
Immunophenotyping and multiplex cytokines (blood sample)
Time Frame
8 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients included in the CORIMUNO-19 cohort (NCT04324047)
COVID-19 cases not requiring ICU at admission with moderate or severe pneumopathy according to the WHO Criteria of severity of COVID pneumopathy:
Moderate cases: Cases meeting all of the following criteria: [Showing fever and respiratory symptoms with radiological findings of pneumonia] AND [Requiring between 3L/min and 5L/min of oxygen to maintain SpO2>97%] OR
Severe cases: Cases meeting any of the following criteria: [Respiratory distress ( ≥ 30 breaths/ min)] OR [Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 > 5L/min] OR [PaO2/FiO2 ≤ 300mmHg]
Exclusion Criteria:
Patients with exclusion criteria to the CORIMUNO-19 cohort.
Respiratory failure requiring non invasive or mechanical ventilation
Patients requiring intensive care
Do-not-resuscitate order (DNR order)
Known hypersensitivity to sarilumab or to any of their excipients.
Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation
Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation
Pregnancy or breastfeeding
Current documented bacterial infection.
Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
Haemoglobin level: no limitation
Platelets (PLT) < 50 G /L
SGOT or SGPT > 5N
Facility Information:
Facility Name
AP-HP Hôpital Avicenne
City
Bobigny
Country
France
Facility Name
AP-HP Hôpital Ambroise Paré
City
Boulogne-Billancourt
Country
France
Facility Name
AP-HP Hôpital Beaujon
City
Clichy
Country
France
Facility Name
AP-HP Hôpital Pitié Salpétrière
City
Paris
Country
France
Facility Name
AP-HP Hôpital Saint Antoine
City
Paris
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Study of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial - CORIMUNO-19 - VIRO
We'll reach out to this number within 24 hrs