A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Oxygenation Improvement
研究概览
简要总结
Lung surfactant is present in the lungs. It covers the alveolar surface where it reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. This study will introduce surfactant to the patients lungs via the COVSurf Drug Delivery System
详细描述
The hypothesis behind the proposed trial of surfactant therapy for COVID-19 infected patients requiring ventilator support is that endogenous surfactant is dysfunctional. This could be due to decreased concentration of surfactant phospholipid and protein, altered surfactant phospholipid composition, surfactant protein proteolysis and/or oedema protein inhibition of surfactant surface tension function and/or oxidative inactivation of surfactant proteins. Variations of these dysfunctional mechanisms have been reported in a range of lung diseases, including cystic fibrosis and severe asthma, and in child and adult patients with ARDS. Our studies of surfactant metabolism in adult ARDS patients showed altered percentage composition of surfactant PC, with decreased DPPC and increased surface tension-inactive unsaturated species, and decreased concentrations of both total PC and phosphatidylglycerol (PG)
The SARS-CoV-2 virus binds to the angiotensin converting enzyme-2 (ACE2) receptor, which is preferentially expressed in the peripheral lung ATII cells. Consequent viral infection of ATII cells could reduce cell number and impair the capacity of the lungs to synthesise and secrete surfactant. This, however, has not yet been demonstrated empirically in COVID-19 patients. If this is the case, then exogenous surfactant administration to the lungs is potential one treatment option to mitigate disease severity in these patients.
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
- •Age ≥18 years old
- •Confirmed COVID-19 positive by PCR
- •Within 24 hours of mechanical ventilation (ETI arm) or within 24 hours of needing either CPAP or NIV (CPAP/NIV arm)
- •Assent or professional assent obtained
排除标准
- •Imminent expected death within 24 hours
- •Specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary haemorrhage)
- •Known or suspected pregnancy
- •Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR < 30)
- •Liver failure
- •Anticipated transfer to another hospital, which is not a study site within 72 hours.
- •Current participation or participation in another study within the last month that in the opinion of the investigator would prevent enrollment for safety purposes.
- •Consent Declined
结局指标
主要结局
Oxygenation Improvement
时间窗: 3 months
To assess the improvement in oxygenation as determined by the PaO2/FiO2 ratio after treatment with study treatment
Pulmonary ventilation Improvement
时间窗: 3 months
To assess the improvement in pulmonary ventilation as determined by the Ventilation Index (VI), where VI = (Respiratory rate X PIP X PaCo2 (mmHg)/ 1000 after study treatment.
IMV Need
时间窗: 3 months
Need for invasive mechanical ventilation (IMV) (CPAP/NIV arm only)
次要结局
- IMV free days(21 days)
- Duration of days(3 months)
- Number of days hospitalised(3 months)
- Mean Change in pulmonary compliance(48 hours)
- Safety Assessment of Frequency and Severity of Adverse Events(3 months)
- Mean Change in PEEP requirement(48 Hours)
- Clinical Improvement(28 days)
- Change in PaO2/FiO2 ratio(3 months)
- Mean Change in ventilatory index(48 hours)
- Mechanical ventilation duration(3 months)
- Length of ICU stay(3 months)
- Ventilator support free days(21 days)
- Mortality(28 days)