A Phase 2 Trial Evaluating Sargramostim in Patients With COVID-19 Associated Acute Hypoxemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 123
- 试验地点
- 11
- 主要终点
- Number of Patients Who Have Been Intubated by Day 14
研究概览
简要总结
The purpose of this research is to find out if a drug (sargramostim) also known as Leukine® could help patient recover faster from COVID-19. Sargramostim may help the lungs recover from the effects of COVID-19, and this research study will help to find this out.
详细描述
This Phase 2 study is designed as a proof of concept study and will randomize 2:1 approximately 120 patients with COVID-19 associated acute hypoxemia: of which 80 patients will receive sargramostim plus standard of care, and 40 patients who will receive standard of care alone. The aim of the study is to determine if inhaled sargramostim, as an adjunct to institutional standard of care, improves clinical outcomes in patients with COVID-19-associated acute hypoxemia. All patients on the sargramostim arm will be treated with 125 mcg inhaled sargramostim twice daily for 5 days, in addition to institutional standard of care. If required, upon progression to an invasive mechanical ventilator, administration of sargramostim may be delivered by intravenous infusion to complete a total of 5 days (including days delivered via inhalation).
GM-CSF is a critical cytokine for healthy pulmonary function and is necessary for the maturation and maintenance of alveolar macrophages. Preclinical studies have shown GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages for their health and normal functioning. Clinical studies of sargramostim in patients with severe sepsis and respiratory dysfunction or acute respiratory distress syndrome have shown improvements in oxygenation and lung compliance.
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
- •Patients aged ≥ 18 years
- •Patients (or legally authorized decision maker) must provide informed consent
- •Test positive for SARS-CoV-2 virus by PCR
- •Admitted to hospital
- •Presence of acute hypoxemia defined as (either or both)
- •saturation below 93% on ≥ 2 L/min oxygen supplementation
- •PaO2/FiO2 below 350
排除标准
- •Patients requiring invasive (mechanical ventilation) or non-invasive (CPAP, BiPAP for hypoxemia) ventilation or ECMO (Note: oxygen supplementation using high flow oxygen systems or low flow oxygen systems would not exclude patients from this study)
- •Intractable metabolic acidosis
- •Cardiogenic pulmonary edema
- •Hypotension requiring use of vasopressors
- •Hyperferritinemia (serum ferritin ≥2,000 mcg/L)
- •White blood cell count > 50,000/mm3
- •Participation in another interventional clinical trial for COVID-19 therapy
- •Highly immunosuppressive therapy or anti-cancer combination chemotherapy within 24 hours prior to first dose of sargramostim
- •Known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product
- •Previous experience of severe and unexplained side effects during aerosol delivery of any kind of medical product
- •Presence of any preexisting illness that, in the opinion of the Investigator, would place the patient at an unreasonably increased risk through participation in this study
- •Pregnant or breastfeeding females
- •Severe or uncontrolled pulmonary comorbid conditions, including systemic steroid dependent asthma, systemic steroid dependent COPD, oxygen dependent COPD, lung transplant, known interstitial lung disease, or cystic fibrosis
研究组 & 干预措施
Sargramostim Arm
Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19
干预措施: Sargramostim (Drug)
Sargramostim Arm
Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19
干预措施: Standard of care (Drug)
Control Arm
Standard of care for COVID-19
干预措施: Standard of care (Drug)
结局指标
主要结局
Number of Patients Who Have Been Intubated by Day 14
时间窗: 1-14 days
Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6
时间窗: 1-6 days
The P(A-a)O2 gradient is a measure of how well the oxygen moves from the lungs into the bloodstream. Patients with a high gradient have less oxygen in the bloodstream.
次要结局
- All Cause 28-day Mortality(1-28 days)
- Number of Patients With Treatment-related Adverse Events(1-58 days)
- Survival Time of Patients(Day 1-90)
- Causes of Death(Day 1-90)
- Number of Patients Requiring Invasive Mechanical Ventilation(Day 1-90)
- Change in Ordinal Scale(1-28 days)
- Number of Participants Wtih Nosocomial Infections(Day 1-90)
- Duration of Hospitalization(Day 1-90)
- Duration of Invasive, Non-invasive and Supplemental Oxygen(Day 1-90)
- Time to Normalization of White Blood Cells and Lymphocytes(Day 1-90)
- Change From Baseline in P/F Ratio(From Day 1 up to Day 6)