A Nested Interventional Cohort Study to Assess the Efficacy and Safety of Adjunctive Humanized Monoclonal Interleukin-6 Receptor Blocker Tocilizumab (TCZ) Therapy to Standard of Care for the Reduction of Hyperinflammation Related Mortality in SARS-Cov2 Positive Patients
试验速览
- 阶段
- 3 期
- 入组人数
- 30
- 主要终点
- All-cause mortality
研究概览
简要总结
This is a cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%.
详细描述
The novel coronavirus, SARS-Cov2/COVID-19, emerged in late 2019 in Wuhan, China. Quickly, SARS-CoV2 spread to all corners of the globe. In March 2020, The World Health Organization (WHO) declared SARS-CoV2/COVID-19 a pandemic. Individuals infected with SARS-CoV2 have a varied clinical presentation, ranging from asymptomatic or mild respiratory symptoms to severe involvement of the lower respiratory tract, with patients requiring mechanical ventilation. A particular point of interest is how the overall severity and clinical outcomes of COVID-19 patients may be associated with the excessive production of pro-inflammatory cytokines, or hyperinflammation, leading to acute respiratory distress syndrome. This state of hyperinflammation may be associated with increased mortality in COVID-19 patients. Tocilizumab, an Interleukin-6 antagonist, may help treat COVID-19 associated hyperinflammation.
This is a nested interventional cohort study of COVID-19 patients with hyperinflammation. It aims to determine the impact of adjunctive Tocilizumab (TCZ) to standard of care on the reduction of hyperinflammation-related mortality in COVID-19. Patients with COVID-19 are at high risk of life-threatening hyperinflammation and death. One in three COVID-19 patients admitted to ICU was found to develop life-threatening hyperinflammation. The risk of death when untreated is estimated to be 50-80%. TCZ treatment may reduce mortality.
Primary objective: To establish that tocilizumab, in addition to standard of care, reduces the 30-day mortality from hyperinflammation in COVID-19 disease significantly compared to no anti-interleukin therapy plus standard of care.
Secondary objectives: To evaluate the addition of tocilizumab therapy to standard of care on a number of secondary outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Age ≥ 18 years
- •All genders
- •Hospitalization for suspected or confirmed SARS-CoV2 infection. COVID-19 diagnosis defined as positive on reverse-transcriptase polymerase chain reaction, with provincial laboratory confirmation.
- •Signs of hyperinflammation (cytokine release syndrome) defined by the presence of any of the following:
- •i. Elevated C-reactive protein (≥70 mg/dl and/or rising since last 24h not due to bacterial infection), ii. Ferritin (>700 mcg/L and/or rising since last 24h),
- •Anti-interleukin treatment indication as per hyperinflammation team
- •Informed consent for participation in the study
排除标准
- •Goal of Care C (palliative care)
- •Known hypersensitivity to TCZ or its components
- •Current systemic immunosuppressive therapy; anti-interleukin 1 or anti-interleukin 6 treatment
- •Known active bacterial or fungal infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment
- •Current or history of bowel perforation or diverticulitis
- •Suspicion of active or latent tuberculosis
- •Pregnant or breastfeeding patient
- •Patients with known prior liver disease
结局指标
主要结局
All-cause mortality
时间窗: Assessed at 30 days post treatment
Mortality status of participants
次要结局
- Ordinal Scale for evaluating subject clinical status at days 3, 8, 15, 30, 60 post treatment.(Assessed at days 3, 8, 15, 30, 60 post treatment)