Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 46
- 试验地点
- 4
- 主要终点
- PaO2/FiO2 ratio
研究概览
简要总结
SARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease that has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of April 1, 2020, there are 874.081 numbers of confirmed cases with 43.290 fatalities. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment.
Key markers implying a fatal outcome are acute respiratory distress syndrome (ARDS)-like disease with pronounced dyspnea, hypoxia and radiological changes in the lung. Senicapoc improves oxygenation and reduces fluid retention, inflammation, and bleeding in the lungs of mice with ARDS-like disease. In cells, there is an antiviral effect of senicapoc.
详细描述
The investigators discovered that in an animal model with a knockout of a potassium channel with intermediate conductance (KCa3.1), the knockout protected against lung damage and accumulation of liquid in the lung. In subsequent studies, the investigators have developed a mouse model showing that genetic deletion of the KCa3.1 channels and senicapoc, a blocker of KCa3.1 channels, protects against the accumulation of liquid in the lung. Moreover, senicapoc treatment possesses anti-inflammatory effects illustrated as lower leukocyte accumulation inside the lungs after injury. Importantly, it also increases the FiO2/PaO2 ratio (ratio of inhaled to blood oxygen), hence preserving lung function in mice with an ARDS-like disease. In addition, there is evidence that senicapoc has antiviral properties. Aarhus University has patented senicapoc for use in the treatment of acute respiratory disease. In this case, respiratory disease is caused by an infection with a coronavirus. Senicapoc has been developed for the treatment of sickle cell disease and has been administered to 500 patients without observation of major treatment-related adverse effects.
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
盲法说明
Senicapoc-treated patients compared to standard treatment
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
- •COVID-19 positive
- •Age ≥18 years
- •Respiratory insufficiency
- •ICU admission
排除标准
- •Severe heart failure (ejection fraction < 30%)
- •Severe renal insufficiency (eGFR < 30 mL/min/1.73m2)
- •Severe hemodynamic instability (noradrenalin dose > 0.3 μg/kg/min)
- •Prior enrollment in the trial
- •Pregnancy
- •Allergy to senicapoc
- •Inability to take enteral medication
- •More than 24 hours since ICU admission
- •Limitations of care
- •Anticipated death within 24 hours
研究组 & 干预措施
Senicapoc
Senicapoc
干预措施: Senicapoc (Drug)
结局指标
主要结局
PaO2/FiO2 ratio
时间窗: Day 3
The PaO2/FiO2 ratio will be calculated based on the arterial gas closest to the time-point of Day 3 after randomization
次要结局
- Ventilator-free days(Day 28)
- Mortality(Day 28)