Prospective, Randomized, Multi-center Phase 2 Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) for the Treatment of Acute Respiratory Distress Syndrome (ARDS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 12
- 主要终点
- Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion
研究概览
简要总结
This was a Phase 2a, randomized, double-blind, placebo-controlled, multi-center trial to assess the safety and efficacy of a single dose of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) infusion in patients with Acute Respiratory Distress Syndrome (ARDS).
详细描述
We carried out a randomized, double-blind placebo-controlled trial of allogeneic bone marrow derived human mesenchymal stromal cells for treatment of moderate to severe ARDS in 60 patients, 40 MSC and 20 placebo, in a 2:1 randomization. This trial is the extension of the Phase 1 pilot trial (NCT01775774). Patients were followed daily for adverse events through day 28, death or hospital discharge, whichever occurs first. Vital status was collected at 6 and 12 months after study enrollment.
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)
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.
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
- •World Health Organization (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
Plasma-Lyte A (placebo)
A single dose of Plasma-Lyte A was administered intravenously over approximately 60-80 minutes.
干预措施: Plasma-Lyte A (Biological)
Human Mesenchymal Stromal Cells (hMSCs)
A single dose of 10 million cells/kg PBW (predicted body weight) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells was administered intravenously over approximately 60-80 minutes.
干预措施: Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells (Biological)
结局指标
主要结局
Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion
时间窗: 6 hours
Within 6 h of study product infusion: * Increase in vasopressor dose to the following values or higher: * Norepinephrine 10 μg/min * Phenylephrine 100 μg/min * Dopamine 10 μg/kg per min * Epinephrine 0.1 μg/kg per min or addition of a third vasopressor * New ventricular tachycardia, ventricular fibrillation or asystole * New cardiac arrhythmia requiring cardioversion * Hypoxaemia requiring an increase in FiO2 of 0·2 or more and an increase in PEEP of 5·0 or more to maintain SpO2 in the target range of 88-95% * Clinical scenario consistent with transfusion incompatibility or transfusion-related infection (eg, urticaria, new bronchospasm)
Numbers of Patients Occurred Any Cardiac Arrest or Death Within 24 Hours of Study Infusion
时间窗: 24 hours
Within 24 h of study product infusion • Any cardiac arrest or death
Numbers of Patients Occurred Any Unexpected Severe Adverse Events (Including All-cause Deaths)
时间窗: 12 months
Safety endpoint: Any unexpected severe adverse events in two groups
次要结局
- PaO2:FiO2 Change From Baseline to Day 3(baseline and day 3)
- Lung Injury Score From Baseline to Day 3(baseline and day 3)
- Oxygenation Index Change From Baseline to Day 2(baseline and day 2)
- SOFA Score Change From Baseline to Day 3(baseline and day 3)
- Number of Patients Death to Day 28(28 days)
- Number of Ventilator-free Days to Day 28(28 days)
- Non-pulmonary Organ-failure-free Days to Day 28(28 days)
- Angiopoietin 2 Change From Baseline to 6 h(baseline and 6 hours)
- Angiopoietin 2 Change From Baseline to 24 h(baseline and 24 hours)
- Mortality to Day 60(60 days)
- Interleukin 6 Change From Baseline to 6 h(baseline and 6 hours)
- Interleukin 6 Change From Baseline to 24 h(baseline and 24 hours)
- Interleukin 8 Change From Baseline to 6 h(baseline and 6 hours)
- Interleukin 8 Change From Baseline to 24 h(baseline and 24 hours)
- RAGE Change From Baseline to 6 h(baseline and 6 hours)
- RAGE Change From Baseline to 24 h(baseline and 24 hours)
研究者
Michael A. Matthay
Principal Investigator
University of California, San Francisco