COVID19, SARS-CoV-2 Infection
Conditions
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.
Interventions
DRUGSarilumab
Sarilumab: 400 mg in a 1 hour - I.V. infusion on D1
DRUGAzithromycin
Azithromycin: oral administration, 500mg on D1 then 250mg QD on D2 to D5 (total duration 5 days)
DRUGHydroxychloroquine
Hydroxychloroquine: oral administration, 600mg QD (200mg TID) from D1 to D10 (total duration 10 days)
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Bayesian open labelled randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
1. Patients with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Survival | 14, 28 and 90 days | Overall survival |
| 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 |
| 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 |
| Oxygen therapy-free days alive | 14 and 28 days | Number of oxygen therapy-free days alive |
| Time to negative viral excretion | 90 days | SARS-CoV-2 viral load measurement by rtPCR |
| Immunophenotyping and multiplex cytokines | 8 days | Immunophenotyping and multiplex cytokines (blood sample) |
| Hospital-free days alive | 14, 28 and 90 days | Number of hospital-free days alive |
Countries
France
Outcome results
None listed