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
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Need for ventilation (including invasive and non invasive ventilation), intensive care or death
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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]
排除标准
- •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
研究组 & 干预措施
Sarilumab
Sarilumab only
干预措施: Sarilumab (Drug)
Sarilumab + Azithromycin + Hydroxychloroquine
Sarilumab combined with Azithromycin and Hydroxychloroquine
干预措施: Hydroxychloroquine (Drug)
Sarilumab + Azithromycin + Hydroxychloroquine
Sarilumab combined with Azithromycin and Hydroxychloroquine
干预措施: Sarilumab (Drug)
Sarilumab + Azithromycin + Hydroxychloroquine
Sarilumab combined with Azithromycin and Hydroxychloroquine
干预措施: Azithromycin (Drug)
结局指标
主要结局
Need for ventilation (including invasive and non invasive ventilation), intensive care or death
时间窗: 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.
次要结局
- Immunophenotyping and multiplex cytokines(8 days)
- Early improvement: OMS progression scale <= 5(4 days)
- Survival(14, 28 and 90 days)
- Oxygen therapy-free days alive(14 and 28 days)
- OMS progression scale(4, 7 and 14 days)
- ICU-free days alive(14, 28 and 90 days)
- Ventilation-free days alive(14 and 28 days)
- Time to negative viral excretion(90 days)
- Hospital-free days alive(14, 28 and 90 days)