Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients - Tocilizumab Trial - CORIMUNO-19 - TOCI (CORIMUNO-TOCI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 228
- 试验地点
- 8
- 主要终点
- Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
研究概览
简要总结
The overall objective of the study is to determine the therapeutic effect and tolerance of Tocilizumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the CORIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
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 —（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
- •Patients belonging to one of the 2 following groups:
- •Group 1: Cases meeting all of the following criteria
- •Requiring more than 3L/min of oxygen
- •OMS/WHO progression scale = 5
- •No Non Invasive Ventilation or High flow
- •Group 2: Cases meeting all of the following criteria
- •Respiratory failure AND (requiring mechanical ventilation OR Non Invasive Ventilation OR High flow)
- •WHO progression scale >=6
- •No do-not-resuscitate order (DNR order)
排除标准
- •Patients with exclusion criteria to the CORIMUNO-19 cohort.
- •Known hypersensitivity to Tocilizumab or to any of their excipients.
- •Pregnancy
- •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
TOCILIZUMAB -- Severe COVID Population (WHO Clinical Progression Scale =5 at baseline)
Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) CPS: Clinical Progression Scale
干预措施: Tocilizumab (Drug)
TOCILIZUMAB -- Critical COVID Population (WHO Clinical Progression Scale >5 at baseline)
Tocilizumab 8mg/kg on day 1 and if no response (no decrease of oxygen requirement) a second injection at day 3 (fixed dose of 400 mg) CPS: Clinical Progression Scale
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Percentage of Participants With WHO Clinical Progression Scale > 5 at Day 4 -- Severe COVID Population (WHO Clinical Progression Scale =5 at Baseline)
时间窗: 4 days
Percentage of participants who has died or needed non-invasive or mechanical ventilation by day 4 (WHO clinical progression scale \> 5). A patient with new do-not-resuscitate order at day 4 will be considered as with a score \> 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
Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 (WHO Clinical Progression Scale =5 at Baseline)
时间窗: Day 1 to Day 14
Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Percentage of non-invasive ventilation, mechanical ventilation or death. Thus, events considered are needing ventilator utilization (mechanical or non-invasive ventilation including high flow oxygen), or death. New do-not-resuscitate (DNR) order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Percentage of Participants With no Improvement in WHO Clinical Progression Scale at Day 4 -- Critical COVID Population ( WHO Clinical Progression Scale >5 at Baseline)
时间窗: 4 days
Results are presented as the percentage not improved, so that an effective treatment would be associated with a decrease in percentage 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
Cumulative Incidence (Percentage of Participants) With Successful Tracheal Extubation at Day 14 -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)
时间窗: Day 1 to Day 14
Cumulative incidence of successful tracheal extubation (defined as duration extubation \> 48h) at day 14 if patients have been intubated before day 14 ; or removal of Non Invasive Ventilation or high flow (for \> 48h) if they were included under oxygen by Non Invasive Ventilation or High flow (score 6) and remained without intubation. Death or new do-not-resuscitate order (if given after the inclusion of the patient) will be considered as a competing event.
次要结局
- Percentage of Participants Surviving (Overall Survival)(14, 28 and 90 days)
- WHO Progression Scale(4, 7 and 14 days)
- Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)(28 days)
- Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency(Day 28, 90)
- Cumulative Incidence (Percentage of Participants) of Discharge From Hospital(28, 90 days)
- Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)(28, 90 days)
- PaO2/FIO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)(day 1 to day 14)