A Phase 1 Multi-center Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stem Cells for the Treatment of Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 4
- 主要终点
- Incidence of Pre-specified Infusion Associated Adverse Events
研究概览
简要总结
This is a Phase 1, open label, dose escalation, multi-center clinical trial of Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells (hMSCs) for the treatment of Acute Respiratory Distress Syndrome (ARDS). The purpose of this study is to assess the safety of hMSCs in patients with ARDS.
详细描述
The primary objective of this study is to assess the safety of intravenous infusion of Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells (hMSCs) in patients with ARDS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 will be eligible for inclusion if they meet all of the below criteria. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:
- •Acute onset (defined below) of:
- •A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio < 200 with at least 8 cm H2O positive end-expiratory airway pressure (PEEP)
- •Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
- •No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.
- •In addition to meeting inclusion criteria, enrollment must occur within 96-hours of first meeting ARDS criteria per the Berlin definition of ARDS.
排除标准
- •Age less than 18 years
- •Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
- •Pregnant or breast-feeding
- •Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
- •Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
- •Moderate to severe liver failure (Childs-Pugh Score > 12)
- •Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
- •Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest).
- •Major trauma in the prior 5 days
- •Lung transplant patient
- •No consent/inability to obtain consent
- •Moribund patient not expected to survive 24 hours
- •WHO Class III or IV pulmonary hypertension
- •Documented deep venous thrombosis or pulmonary embolism within past 3 months
- •No arterial line/no intent to place an arterial line
- •No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
- •Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
研究组 & 干预措施
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
A dose-escalation with 3 cohorts with 3 subjects/cohort who receive doses of 1, 5 and 10 million cells/kg predicted body weight (PBW). Proceed from lower dose to next higher dose if no safety concerns for each cohort.
干预措施: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells (Biological)
结局指标
主要结局
Incidence of Pre-specified Infusion Associated Adverse Events
时间窗: 24 hours
Any of the following occurring within 6 h of mesenchymal stem-cell infusion: * Addition of a third vasopressor or an increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg per min * Phenylephrine: 100 μg per min * Dopamine: 10 μg/kg per min * Epinephrine: 0·1 μg/kg per min * Hypoxaemia requiring an increase in the fraction of inspired oxygen of ≥0·2 and increase in positive end-expiratory airway pressure level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95% * New cardiac arrhythmia requiring cardioversion * New ventricular tachycardia, ventricular fi brillation, or asystole * A clinical scenario consistent with transfusion incompatibility or transfusion-related infection * Cardiac arrest or death within 24 h of mesenchymal stem-cell infusion
次要结局
- Incidence of Severe Adverse Events (SAEs)(Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.)
- Ventilator Free Days at Study Day 28(time of initiating unassisted breathing to day 28)
- Duration of Vasopressor Use (Days)(28 days)
- ICU Free Days to Day 28(28 days after study enrollment)
- Hospital Survival to Day 60(60 days after randomization)
- Mortality at Hospital Discharge(From study enrollment to Hospital discharge)
研究者
Michael A. Matthay
Prinicpal Investigator
University of California, San Francisco