Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Number of Subjects With Serious Adverse Events by 31 Days After First Infusion
研究概览
简要总结
The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).
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, Care Provider, Investigator)
盲法说明
Double-Blinding Trial
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 >/= 18 years old diagnosed with COVID-19 (as evaluated by PCR test confirming infection with SARS-CoV-2) will be eligible for inclusion if they meet all of the below criteria. Inclusion criteria must all be present within a 24-hour time period at the time of enrollment:
- •Patient currently hospitalized
- •Aged ≥ 18 years
- •Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
- •Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
- •PaO2/FiO2 ratio < 300 mmHg
- •Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
- •Hypoxemia requiring an increase in the fraction of inspired oxygen (FiO2) of ≥ 20% AND an increase in positive end-expiratory airway pressure (PEEP) level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95%, or requirement for escalation from oxygen therapy to invasive mechanical ventilation
排除标准
- •PaO2/FiO2 ≥ 300 at the time of enrollment
- •A previous MSC infusion not related to this trial
- •History of Pulmonary Hypertension (WHO Class III/IV)
- •History of left atrial hypertension or decompensated left heart failure.
- •Pregnant or lactating patient
- •Unstable arrhythmia
- •Patients with previous lung transplant
- •Patients currently receiving chronic dialysis
- •Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
- •Presence of any active malignancy (except non-melanoma skin cancer)
- •Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
- •Moderate to severe liver disease (AST and ALT >5 X ULN)
- •Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
- •Baseline QT prolongation
- •Moribund patient not expected to survive > 24 hours
结局指标
主要结局
Number of Subjects With Serious Adverse Events by 31 Days After First Infusion
时间窗: 31 days
The number of subjects experiencing serious adverse events by 31 days after the first infusion (corresponding to 28 days after the last infusion).
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 90 days
Total number of adverse events and serious adverse events as assessed by treating physician
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity
时间窗: 90 days
Total number of adverse events plus serious adverse events categorized by severity.
Subjects With Adverse Events and Serious Adverse Events by Severity
时间窗: 90 days
Total number of subjects with adverse events and serious adverse events categorized by severity.
Number of Participants With Pre-Specified Infusion Associated Adverse Events
时间窗: 6 and 24 hours
Safety as defined by the number of pre-specified infusion associated adverse events as assessed by treating physician. Any of the following occurring within 6 h post each infusion: 1. An increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg/min * Phenylephrine: 100 μg/min * Dopamine: 10 μg/kg/min * Epinephrine: 10 μg/min 2. In patients receiving mechanical ventilation: worsening hypoxemia, as assessed by a requirement for an increase of PEEP by 5 cm H2O over baseline, or requirement to increase FiO2 of \>20%. 3. In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation. 4. New cardiac arrhythmia requiring cardioversion 5. New ventricular tachycardia, ventricular fibrillation, or asystole 6. A clinical scenario consistent with transfusion incompatibility or transfusion-related infection 7. Cardiac arrest or death within 24h post infusion
Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90
时间窗: 90 days
Safety will be reported as the percentage of participants experiencing serious adverse events through Day 90 as assessed by treating physician.
Subjects With Adverse Events by Relatedness to Treatment
时间窗: 90 days
Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional
Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment
时间窗: 90 days
Total number of adverse events and serious adverse events categorized by relatedness to treatment defined by a medical professional.
次要结局
- Potassium(day 6)
- Creatinine(day 6)
- Survival at 60 Days Post First Infusion(60 days)
- Oxygenation Index (OI)(day 6)
- White Blood Cell Count (WBC)(day 6)
- Glomerular Filtration Rate(day 6)
- Total Protein(Day 6)
- Sodium(day 6)
- Ventilator-Free Days Throughout 90 Days(90 days or hospital discharge, whichever is earlier)
- Time to Recovery(31 days)
- Positive End-Expiratory Pressure (PEEP) and Plateau Pressure (Pplat)(day 6)
- Sequential Organ Failure Assessment (SOFA) Scores(Day 6)
- Hematocrit(day 6)
- Survival at 31 Days Post First Infusion(31 Days)
- Ventilator-Free Days Throughout 28 Days Post Second Infusion(28 days post second infusion)
- Respiratory Rate and Oxygenation Index (ROX Index)(day 6)
- Smell Identification Test (SIT) Scores(90 days)
- Platelets Count(day 6)
- Hemogoblin(day 6)
- Lymphocytes(day 6)
- Alanine Aminotransferase or Serum Glutamate-pyruvate Transaminase (ALT or SGPT)(day 6)
- Calcium(day 6)
- Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 6 Post First Infusion(day 6)
- Neutrophils(day 6)
- Glucose(day 6)
- Alkaline Phosphatase(day 6)
- Aspartate Aminotransferase or Serum Glutamic Oxaloacetic Transaminase (AST or SGOT)(day 6)
- Carbon Dioxide (CO2)(day 6)
- D-dimer Levels(day 6)
- 25-Hydroxy Vitamin D Levels(day 6)
- Tumor Necrosis Factor-beta (TNFβ)(day 6)
- Albumin(day 6)
- Blood Urea Nitrogen (BUN)(day 6)
- Arachidonic Acid/Eicosapentaenoic Acid (AA/EPA) Ratio(day 6)
- Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 14 Post First Infusion(day 14)
- Number of Participants With Positive, Negative, or Borderline Serology Testing for SARS-CoV-2 IgM/IgG(day 14 post first infusion)
- Chloride(day 6)
- C-Reactive Protein Levels(day 6)
- Number of Participants Reporting Panel Reactive Antibody (PRA) Positivity at Day 3 Post First Infusion(day 3 post first infusion)
- Total Bilirubin(day 6)
- Tumor Necrosis Factor-alpha (TNFα)(day 6)
- Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2)(day 6)
- Viral Load by SARS-CoV-2 RT-PCR(day 6)
研究者
Camillo Ricordi
Professor of Surgery and Chief, Division of Cellular Transplantation
University of Miami