CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection, Nested In The CORIMUNO-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 161
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- 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 Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the CORIMUNO-19 cohort. Anakinra 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 Anakinra will receive standard of cares. Outcomes of Anakinra -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 with C-reactive protein level (CRP) > 25 mg / L the day or the day before the infusion)
- •Patients belonging to one of the 2 following groups:
- •Group 1: patients meeting all of the following criteria: 1) Requiring more than 3L/min of oxygen; 2) WHO progression scale = 5; 3) No non invasive ventilation or High flow
- •Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR non invasive ventilation OR High flow), with a WHO progression scale ≥ 6, and no do-not-resuscitate (DNR) order
排除标准
- •Patients with exclusion criteria to the CORIMUNO-19 cohort.
- •Known hypersensitivity to Anakinra 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:
- •Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
- •Haemoglobin level: no limitation
- •Platelets (PLT) < 50 G /L
- •SGOT or SGPT > 5N
- •Severe renal insufficiency with Glomerular filtration rate < 30 ml / mn
研究组 & 干预措施
ANAKINRA -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline)
Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5).
In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
干预措施: Anakinra (Drug)
ANAKINRA -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline)
Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5).
In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level > 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter
干预措施: Anakinra (Drug)
结局指标
主要结局
Percentage of Participants With Non-invasive Ventilation, Mechanical Ventilation or Death at Day 14 -- Severe COVID Population (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 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.
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 (percentage) 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.
Percentage of Participants With a Decrease of at Least One Point in WHO Clinical Progression Scale Score at Day 4 -- Critical COVID Population (WHO Clinical Progression Scale >5)
时间窗: 4 days
Percentage of patients with a decrease of WHO score of at least 1 point at day 4
次要结局
- WHO Clinical Progression Scale(4, 7, 14, 28 days)
- Percentage of Participants Surviving (Overall Survival)(14, 28 and 90 days)
- Mean of Ventilator Free-days at Day 28 -- Critical COVID Population (WHO-clinical Progression Scale >5 at Baseline)(28 days)
- PaO2/FiO2 Ratio -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)(day 1 to day 14)
- Cumulative Incidence (Percentage of Participants) of Oxygen Supply Independency(28 and 90 days)
- Cumulative Incidence (Percentage of Participants) of Discharge From Hospital(28 days)
- Cumulative Incidence (Percentage of Participants) of Intensive Care Unit Discharge -- Critical COVID Population (WHO Clinical Progression Scale >5 at Baseline)(28 and 90 days)