C5 Complement Inhbition Using Ravulizumab for the Treatment of COVID-19 Induced Thrombotic Microangiopathy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Assess the efficacy of ravulizumab to ameliorate SARS-CoV-2 (COVID-19)-induced acute kidney injury manifesting as thrombotic microangiopathy.
研究概览
简要总结
Ultomiris (Ravulizumab), is a monoclonal antibody that specifically targets terminal complement products and is proposed for the treatment of COVID-19 induced microvasculature injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute kidney injury (AKI). Ravulizumab is to be used for participants with a confirmed diagnosis of COVID-19 who clinically or diagnostically present with deteriorating renal function. Ravulizumab causes immediate and sustained inhibition of the terminal complement cascade. The use of ravulizumab could ameliorate COVID-19 induced kidney injury due to TMA, shorten hospital stay, and improve the overall survival.
详细描述
The novel coronavirus (COVID 19) is responsible for the current pandemic with the numbers of diagnoses and fatalities rising daily. It is reported that of those requiring medical intensive care almost 49% will expire prior hospital discharge. The initial peak of hospitalized patients in Boston, MA occurred on April 15, 2020 however new presentations continue to manifest at a local and national level.
The exact pathophysiology is still not clear. There are various theories that explain the pathophysiology which includes but is not limited to direct viral damage via the angiotensin-converting enzyme 2 receptor, systemic inflammatory response with cytokine storm, and aggravated hypoxia.
Recently, it has been observed that signs and symptoms of severe COVID 19 describe complement-mediated TMA rather than the sepsis induced coagulopathy. This strengthens the hypothesis that complement inhibition by C5a inhibitor, Ultomiris (ravulizumab) could ameliorate COVID 19 induced TMA, improve renal function, shorten the hospital stay and reduce the overall mortality.
In those affected with severe or fatal COVID-19, there is evidence of end-organ damage with acute kidney injury which has heightened the interest in studying the excessive cytokine release and its overall effect in the form of multi-organ failure.
Ultomiris (Ravulizumab) is a long acting second generation monoclonal antibody against a terminal complement product C5a and is FDA approved for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and atypical hemolytic uremic syndrome.The benefit of Ultomiris has not been clinically evaluated in COVID 19 induced TMA.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or Females 18 years of age or above and weighing 40kg or above at the time of providing informed consent.
- •A clinical diagnosis of thrombotic microangiopathy will then be applied to include the following criteria: i) D-dimer > 100% the upper limit of the reference range and ii) serum creatinine >25% of the normal range or iii) >25% increase from patient's baseline serum creatinine.
- •Diagnosis of SARS-CoV-2 infection within 90 days prior to enrollment
排除标准
- •Participant is not expected to survive more than 24 hours.
- •Participant has an unresolved Neisseria Meningitides infection.
- •Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.
研究组 & 干预措施
Interventional arm
ravulizumab
干预措施: Ravulizumab (Drug)
结局指标
主要结局
Assess the efficacy of ravulizumab to ameliorate SARS-CoV-2 (COVID-19)-induced acute kidney injury manifesting as thrombotic microangiopathy.
时间窗: 30 days
50% improvement in estimated glomerular filtration rate compared to conventional therapy within 30 days of treatment for COVID-19-induced acute kidney injury.
次要结局
- Evaluation of pharmacokinetics of ravulizumab in participants with COVID-19(120 days)
研究者
Andrew Michael Siedlecki
asistant professor
Brigham and Women's Hospital