Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 and Increased Inflammatory Markers: a Phase III Randomized Clinical Trial (COVID-19 Coalition Brazil VI) (TOCIBRAS)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 129
- 试验地点
- 7
- 主要终点
- Evaluation of clinical status
研究概览
简要总结
The trial evaluates the efficacy and safety of Tocilizumab, which rapidly reduces the inflammation process through inhibition of IL-6 in patients with moderate to severe COVID-19 with increased inflammatory markers. There will be two arms in the trial, one receiving the best supportive care, and the other receiving it plus tocilizumab. Patients will be followed until Day 29 after randomization.
详细描述
Coalition VI (TOCIBRÁS) is a prospective phase III randomized controlled trial that evaluates the efficacy and safety of Tocilizumab, an antibody anti-IL-6 receptor in patients with moderate to severe COVID-19 with increased inflammatory markers. This is a superiority open-label study with two arms. The control arm receives the best supportive care, and the experimental receives it plus tocilizumab. Randomization is done centrally by REDCap 1:1. Patients will be followed until Day 29 after randomization.
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
- •Male and females with 18 years and older
- •Confirmed diagnosis of SARS-CoV 2 infection
- •More than 3 days of symptoms related to COVID-19
- •Computed tomography (or Chest X-Ray) with COVID-19 alterations
- •Both of the criteria
- •Need for oxygen supplementation to keep SPO2 > 93% OR need for mechanical ventilation for less than 24 hours before the randomization
- •At least two of the following inflammatory tests above the cutoff :
- •D-dimer > 1,000 ng/mL
- •Reactive C protein > 5 mg/dL
- •Ferritin > 300 mg/dL
- •Lactate dehydrogenase > upper level limit
排除标准
- •Need for mechanical ventilation for 24 hours or more before the randomization
- •Hypersensitivity to tocilizumab
- •Patients without therapeutic perspective or in palliative care
- •Active non controlled infections
- •Other clinical conditions that contraindicate tocilizumab, according to the assistant physician
- •Low neutrophils count (< 0.5 x 109/L)
- •Low platelets count (< 50 x 109/L)
- •Liver disease, cirrhosis or elevated AST or ALT above 5 times the upper level limit
- •Renal disease with estimate glomerular filtration below 30 mL/min/1.72 m2 (MDRD or CKD-EPI scores)
- •Active diverticulitis
- •Breastfeeding women
- •Pregnancy
研究组 & 干预措施
Tocilizumab
Single-dose tocilizumab of 8 mg/kg (maximum dose of 800mg). Best supportive care.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Evaluation of clinical status
时间窗: Day 15 of the trial
Evaluation of clinical status of patients on day 15 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)
次要结局
- Incidence of adverse events(29 days after the randomization (specific evaluations at D8, D15 and D29))
- Hospital Mortality(29 days after the randomization)
- Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale(29 days after the randomization (evaluations at D8 and D15))
- Evaluation of clinical status(29 days after the randomization (evaluations at D8 and D29))
- Time until oxygen support independence(29 days after the randomization)
- Need of mechanical ventilation support(29 days after the randomization)
- Duration of hospitalization(29 days after the randomization)
- All-cause mortality(29 days after the randomization)
- Ventilator free days(29 days after the randomization)
- Days to mechanical ventilation support.(29 days after the randomization)
- Other infections(29 days after the randomization)
- Incidence of thromboembolic events(29 days after the randomization)
研究者
Dr Rozana Mesquita Ciconelli
Head of research team
Beneficência Portuguesa de São Paulo