Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Adverse events (patient) - Decrease in oxygenation
研究概览
简要总结
The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety.
详细描述
The most severe patients infected by the virus that causes COVID-19 develop severe respiratory failure (called ARDS) and require mechanical ventilation in the intensive care unit to help maintain oxygen delivery to the blood. Often these patients further deteriorate while on mechanical ventilation. This trial will determine the feasibility and safety of a therapy that can potentially improve lung function, reduce the need for mechanical ventilation and hopefully impact mortality.
Adult patients with COVID-19 induced respiratory failure will be randomly assigned to receive either standard treatment or standard treatment plus exogenous surfactant. If enrolled in the latter, exogenous surfactant will be instilled into the lungs within 48 hours of intubation.
The study is founded on extensive research on ARDS for over 30 years, leading to evidence suggesting that exogenous surfactant administration may be beneficial in this disease. Importantly, exogenous surfactant is already utilized all over the world to reduce mortality in preterm infants. When tested in adults with ARDS, it was shown to be well tolerated and safe. Furthermore, clinical and laboratory evidence suggests that this therapy may be most effective in patients with a direct lung infection, and when administered shortly after the patient is intubated. In this study, twenty patients who are proven COVID-19 positive and require MV due to progressive respiratory failure will be randomized to receive either 1) exogenous surfactant (BLES) as soon as possible and within 48 hours of intubation and stabilization, or 2) treatment as usual (will not be treated with surfactant). The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety. Should the investigators obtain promising results, the data obtained from this study will be used to develop a large trial to test the impact of this therapy on the clinical outcomes, including mortality, associated with COVID-19.
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 over 18 years
- •definitive proof of COVID-19 infection within 48 hours of intubation
- •acute respiratory failure with PaO2/FiO2 < 300 requiring intubation
排除标准
- •known or high suspicion of pre-existing heart failure, unstable angina
- •presence of severe shock with hemodynamic instability despite escalating vasopressors
- •severe, underlying lung disease (COPD, pulmonary fibrosis, lung cancer. etc.)
- •Concurrent treatments are delivered directly into the lung (ie anesthetics etc)
- •Diagnosis of pulmonary hemorrhage
研究组 & 干预措施
BLES treatment
For patients randomized to the treatment arm, exogenous BLES will be administered as soon as possible and within 48 hours of intubation. BLES will be administered daily for up to 3 doses, or until the patient is liberated from the ventilator.
干预措施: Bovine Lipid Extract Surfactant (Drug)
结局指标
主要结局
Adverse events (patient) - Decrease in oxygenation
时间窗: 3 days post-randomization
Count of any decreases in oxygenation, expressed as PaO2 (mmHg) / FiO2 (% oxygen as a decimal), of greater than 20% during the BLES treatment and up to 30 minutes post-treatment. Change will be calculated relative to pre-treatment values.
Adverse event (healthcare worker) - Circuit breach
时间窗: 3 days post-randomization
Number of circuit breaches. Count of any circuit breach immediately prior to and during each BLES treatment procedure will be recorded.
Adverse events (patient) - Decrease in hemodynamics
时间窗: 3 days post-randomization
Count of any decrease in mean arterial blood pressure \>10 mmHg or requirement for \>20% increase in vasopressor dose during the BLES procedure and up to 30 minutes post-treatment. Change will be calculated relative to the pre-treatment values.
Adverse event (healthcare worker) - COVID-19 symptoms
时间窗: 2 weeks post-randomization
Count of healthcare personnel involved in the BLES procedure developing symptoms and testing positive for COVID-19.
次要结局
- IL-1 beta levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- Ventilated days(From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days)
- IFN gamma levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- MCP-1 levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- Length of ICU stay(From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days)
- Mortality(30 days)
- GM-CSF levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- Change in oxygenation(Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.)
- Change in Lung compliance(Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.)
- G-CSF levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- IL-4 levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- IL-6 levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- I levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- Length of hospital stay(From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days)
- IL-10 levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))
- TNF alpha levels (serum inflammatory biomarker)(ICU day 0, 1, 3 and 7 (7 days))