Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 1 Multi-center Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stem Cells for the Treatment of Acute Respiratory Distress Syndrome

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: Age less than 18 years Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS Pregnant or breast-feeding Prisoner 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells<br>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. | Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells<br>* Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Pre-specified Infusion Associated Adverse Events | 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 | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Severe Adverse Events (SAEs) | The number of participants with a severe adverse event during the study was assessed. | 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 | Ventilator Free Days (VFDs) to day 28 were defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject received assisted breathing at day 27 or died prior to day 28, a value of zero VFDs was given. | time of initiating unassisted breathing to day 28 | 
| Duration of Vasopressor Use (Days) | Days on vasopressor to day 28 after study enrollment | 28 days | 
| ICU Free Days to Day 28 |  | 28 days after study enrollment | 
| Hospital Survival to Day 60 | The number of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60. | 60 days after randomization | 
| Mortality at Hospital Discharge | The number of patients expired at hospital discharge. | From study enrollment to Hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Acute Lung Injury, Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells