Mesenchymal Stromal Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 223
- 试验地点
- 21
- 主要终点
- Number of all-cause mortality
研究概览
简要总结
The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS.
The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.
详细描述
This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial. Randomization will be stratified by clinical center and by moderate versus severe ARDS. The study is designed to have three interim analyses for stopping accrual early for efficacy and futility when 30%, 45% and 60% of the 300 patients have reached the primary endpoint using Bayesian predictive probabilities.
Patients will be randomized in a 1:1 allocation to intravenous infusion of MSCs (remestemcel-L) plus standard of care versus placebo plus standard of care for the treatment of COVID-19 related ARDS:
- Group 1: 2x10^6 MSC/kg of body weight plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day)
- Group 2: Placebo (Plasma-Lyte) plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day) (control)
MSCs and placebo will initially be administered intravenously in the dose defined above at randomization. The rate of infusion may be tailored to the patient's respiratory status and fluid status, but the duration of infusion should not exceed 60 minutes.
Patients will be followed for 90 days post randomization, with assessment of pulmonary symptoms at 6 and 12 months.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Remestemcel-L Plus Standard of Care
Intravenous infusion of remestemcel-L 2x10^6 MSC/kg of body weight plus standard of care
干预措施: Remestemcel-L (Biological)
Placebo Plus Standard of Care
Placebo (Plasma-Lyte) plus standard of care
干预措施: Placebo (Drug)
结局指标
主要结局
Number of all-cause mortality
时间窗: 30 days
Number of all-cause mortality within 30 days of randomization.
次要结局
- Number of days alive off mechanical ventilatory support(60 days)
- Number of participants alive at day 60(60 days)
- Number of participants alive at day 90(90 days)
- Number of participants alive at 12 Months(12 Months)
- Number of participants with resolution and/or improvement of ARDS(30 days)
- Severity of ARDS(baseline and 30 days)
- Length of stay(12 months)
- Readmissions(12 months)
- Length of Stay in Intensive Care Unit(12 months)
- Change in plasma hs-CRP concentration(baseline and 21 days)
- Number of participants alive at day 7(7 days)
- Number of participants alive at day 14(14 days)
- Number of adverse events(30 days)
- Clinical Improvement Scale(30 days)
- Change in serum hs-CRP concentration(baseline and 30 days)
- Change in IL-6 inflammatory marker level(baseline and 30 days)
- Change in IL-8 inflammatory marker level(baseline and 30 days)
- Change in TNF-alpha inflammatory marker level(baseline and 30 days)
- Pulmonary symptoms(12 months)
研究者
Annetine Gelijns
Chair, Department of Population Health Science & Policy
Icahn School of Medicine at Mount Sinai