Clinical trial NCT04341870: Study of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients: Sarilumab, Azithromycin, Hydroxychloroquine Trial - CORIMUNO-19 - 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
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: COVID19
SARS-CoV-2 Infection
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Bayesian open labelled randomized clinical trial
Primary purpose: TREATMENT

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.


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:

1. Patients with exclusion criteria to the CORIMUNO-19 cohort.
2. Respiratory failure requiring non invasive or mechanical ventilation
3. Patients requiring intensive care
4. Do-not-resuscitate order (DNR order)
5. Known hypersensitivity to sarilumab or to any of their excipients.
6. Known contra-indication to hydroxychloroquine or chloroquine: including hypersensitivity/allergy, retinopathy, G6PD deficiency and QT prolongation
7. Known contra-indication to azithromycin: including hypersensitivity/allergy and QT prolongation
8. Pregnancy or breastfeeding
9. Current documented bacterial infection.
10. 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

Primary outcomes:
measure: Need for ventilation (including invasive and non invasive ventilation), intensive care or death
timeFrame: 14 days
Secondary outcomes:
measure: Early improvement: OMS progression scale <= 5
timeFrame: 4 days
measure: OMS progression scale
timeFrame: 4, 7 and 14 days
measure: Survival
timeFrame: 14, 28 and 90 days
measure: ICU-free days alive
timeFrame: 14, 28 and 90 days
measure: Ventilation-free days alive
timeFrame: 14 and 28 days
measure: Hospital-free days alive
timeFrame: 14, 28 and 90 days
measure: Oxygen therapy-free days alive
timeFrame: 14 and 28 days
measure: Time to negative viral excretion
timeFrame: 90 days
measure: Immunophenotyping and multiplex cytokines
timeFrame: 8 days
Other outcomes:
Locations:
city: Bobigny
country: France
facility: AP-HP Hôpital Avicenne
city: Boulogne-Billancourt
country: France
facility: AP-HP Hôpital Ambroise Paré
city: Clichy
country: France
facility: AP-HP Hôpital Beaujon
city: Paris
country: France
facility: AP-HP Hôpital Pitié Salpétrière
city: Paris
country: France
facility: AP-HP Hôpital Saint Antoine
Study officials:
References: