Study of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial - CORIMUNO-19 - VIRO
- Conditions
- COVID19SARS-CoV-2 Infection
- Interventions
- Registration Number
- NCT04341870
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 27
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Patients included in the CORIMUNO-19 cohort (NCT04324047)
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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]
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Patients with exclusion criteria to the CORIMUNO-19 cohort.
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Respiratory failure requiring non invasive or mechanical ventilation
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Patients requiring intensive care
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Do-not-resuscitate order (DNR order)
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Known hypersensitivity to sarilumab or to any of their excipients.
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Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation
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Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation
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Pregnancy or breastfeeding
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Current documented bacterial infection.
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sarilumab Sarilumab Sarilumab only Sarilumab + Azithromycin + Hydroxychloroquine Sarilumab Sarilumab combined with Azithromycin and Hydroxychloroquine Sarilumab + Azithromycin + Hydroxychloroquine Hydroxychloroquine Sarilumab combined with Azithromycin and Hydroxychloroquine Sarilumab + Azithromycin + Hydroxychloroquine Azithromycin Sarilumab combined with Azithromycin and Hydroxychloroquine
- Primary Outcome Measures
Name Time Method Need for ventilation (including invasive and non invasive ventilation), intensive care or death 14 days 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
Name Time Method Oxygen therapy-free days alive 14 and 28 days Number of oxygen therapy-free days alive
Immunophenotyping and multiplex cytokines 8 days Immunophenotyping and multiplex cytokines (blood sample)
Early improvement: OMS progression scale <= 5 4 days 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 14, 28 and 90 days Overall survival
OMS progression scale 4, 7 and 14 days 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
ICU-free days alive 14, 28 and 90 days Number of ICU-free days alive
Ventilation-free days alive 14 and 28 days Number of ventilation(invasive or non invasive)-free days alive
Time to negative viral excretion 90 days SARS-CoV-2 viral load measurement by rtPCR
Hospital-free days alive 14, 28 and 90 days Number of hospital-free days alive
Trial Locations
- Locations (5)
AP-HP Hôpital Beaujon
🇫🇷Clichy, France
AP-HP Hôpital Pitié Salpétrière
🇫🇷Paris, France
AP-HP Hôpital Avicenne
🇫🇷Bobigny, France
AP-HP Hôpital Saint Antoine
🇫🇷Paris, France
AP-HP Hôpital Ambroise Paré
🇫🇷Boulogne-Billancourt, France