Back to resultsHuman Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome (START)
Primary Purpose
Acute Respiratory Distress Syndrome
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring Acute Respiratory Distress Syndrome, Acute Lung Injury, Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
Eligibility Criteria
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)
Sites / Locations
- University of California San Francisco Medical Center
- Stanford University Medical Center
- Massachusetts General Hospital
- University of Pittsburgh Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Incidence of Severe Adverse Events (SAEs)
The number of participants with a severe adverse event during the study was assessed.
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.
Duration of Vasopressor Use (Days)
Days on vasopressor to day 28 after study enrollment
ICU Free Days to Day 28
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.
Mortality at Hospital Discharge
The number of patients expired at hospital discharge.
Full Information
NCT ID
NCT01775774
First Posted
January 18, 2013
Last Updated
May 2, 2017
Sponsor
Michael A. Matthay
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Massachusetts General Hospital, Stanford University, University of Pittsburgh, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT01775774
Brief Title
Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome
Acronym
START
Official Title
A Phase 1 Multi-center Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stem Cells for the Treatment of Acute Respiratory Distress Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Michael A. Matthay
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Massachusetts General Hospital, Stanford University, University of Pittsburgh, University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
Acute Respiratory Distress Syndrome, Acute Lung Injury, Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells
Intervention Description
Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.
Primary Outcome Measure Information:
Title
Incidence of Pre-specified Infusion Associated Adverse Events
Description
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
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Incidence of Severe Adverse Events (SAEs)
Description
The number of participants with a severe adverse event during the study was assessed.
Time Frame
Investigators conducted daily assessments for the presence of adverse events (AE) from enrollment through study day 28 or hospital discharge, whichever occurred first.
Title
Ventilator Free Days at Study Day 28
Description
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 Frame
time of initiating unassisted breathing to day 28
Title
Duration of Vasopressor Use (Days)
Description
Days on vasopressor to day 28 after study enrollment
Time Frame
28 days
Title
ICU Free Days to Day 28
Time Frame
28 days after study enrollment
Title
Hospital Survival to Day 60
Description
The number of subjects alive at study day 60. Those subjects discharged home prior to day 60 were counted as alive at day 60.
Time Frame
60 days after randomization
Title
Mortality at Hospital Discharge
Description
The number of patients expired at hospital discharge.
Time Frame
From study enrollment to Hospital discharge
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25529339
Citation
Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17.
Results Reference
result
PubMed Identifier
25593740
Citation
Liu KD, Wilson JG, Zhuo H, Caballero L, McMillan ML, Fang X, Cosgrove K, Calfee CS, Lee JW, Kangelaris KN, Gotts JE, Rogers AJ, Levitt JE, Wiener-Kronish JP, Delucchi KL, Leavitt AD, McKenna DH, Thompson BT, Matthay MA. Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome. Ann Intensive Care. 2014 Jul 3;4:22. doi: 10.1186/s13613-014-0022-z. eCollection 2014.
Results Reference
derived
PubMed Identifier
24891325
Citation
Asmussen S, Ito H, Traber DL, Lee JW, Cox RA, Hawkins HK, McAuley DF, McKenna DH, Traber LD, Zhuo H, Wilson J, Herndon DN, Prough DS, Liu KD, Matthay MA, Enkhbaatar P. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax. 2014 Sep;69(9):819-25. doi: 10.1136/thoraxjnl-2013-204980. Epub 2014 Jun 2.
Results Reference
derived
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Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome
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