Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome

Phase 1

Completed

Conditions: Acute Respiratory Distress Syndrome

Interventions: Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

Registration Number: NCT01775774

Lead Sponsor: Michael A. Matthay

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Pre-specified Infusion Associated Adverse Events	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

Secondary Outcome Measures

Name	Time	Method
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.	The number of participants with a severe adverse event during the study was assessed.
Ventilator Free Days at Study Day 28	time of initiating unassisted breathing to 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.
Duration of Vasopressor Use (Days)	28 days	Days on vasopressor to day 28 after study enrollment
ICU Free Days to Day 28	28 days after study enrollment
Hospital Survival to Day 60	60 days after randomization	The number of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.
Mortality at Hospital Discharge	From study enrollment to Hospital discharge	The number of patients expired at hospital discharge.

Trial Locations

Locations (4): University of California San Francisco Medical Center
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San Francisco, California, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
Stanford University Medical Center
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Stanford, California, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States