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Human Mesenchymal Stromal Cells For Acute Respiratory Distress Syndrome (START) (START)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02097641
Recruitment Status : Completed
First Posted : March 27, 2014
Results First Posted : April 10, 2019
Last Update Posted : April 10, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Massachusetts General Hospital
Stanford University
University of Pittsburgh
University of Minnesota
Ohio State University
Information provided by (Responsible Party):
Michael A. Matthay, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE March 19, 2014
First Posted Date  ICMJE March 27, 2014
Results First Submitted Date  ICMJE January 15, 2019
Results First Posted Date  ICMJE April 10, 2019
Last Update Posted Date April 10, 2019
Actual Study Start Date  ICMJE March 15, 2014
Actual Primary Completion Date March 9, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
  • Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 12 months ]
    Safety endpoint: Any unexpected severe adverse events in two groups
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2014)
  • Incidence of pre-specified infusion associated events occurring within 6 hours of study infusion [ Time Frame: 6 hours ]
  • Any cardiac arrest or death within 24 hours of study infusion [ Time Frame: 24 hours ]
  • Any unexpected severe adverse events in two groups [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
  • PaO2:FiO2 Change From Baseline to Day 3 [ Time Frame: baseline and day 3 ]
    Efficacy endpoint: PaO2:FiO2 change from baseline to day 3
  • Lung Injury Score From Baseline to Day 3 [ Time Frame: baseline and day 3 ]
    Murray score for acute lung injury. The range is 0 to 4. The higher score, the worst outcome.
  • Oxygenation Index Change From Baseline to Day 2 [ Time Frame: baseline and day 2 ]
    Oxygenation index with the following validated measure of respiratory function: FiO2 (%) x mean airway pressure / PaO2
  • SOFA Score Change From Baseline to Day 3 [ Time Frame: baseline and day 3 ]
    Sequential organ failure assessment score (SOFA). The SOFA score ranges from 0 to 24. The higher, the worse.
  • Number of Patients Death to Day 28 [ Time Frame: 28 days ]
    Efficacy endpoint: all-cause mortality at day 28
  • Mortality to Day 60 [ Time Frame: 60 days ]
    Efficacy endpoint: all-cause mortality at day 60
  • Number of Ventilator-free Days to Day 28 [ Time Frame: 28 days ]
    Efficacy endpoint: Number of ventilator-free days to day 28.
  • Non-pulmonary Organ-failure-free Days to Day 28 [ Time Frame: 28 days ]
    Efficacy endpoint: Non-pulmonary organ-failure-free days to day 28
  • Angiopoietin 2 Change From Baseline to 6 h [ Time Frame: baseline and 6 hours ]
    Biological markers of endothelial injury: angiopoietin 2
  • Angiopoietin 2 Change From Baseline to 24 h [ Time Frame: baseline and 24 hours ]
    Biological markers of endothelial injury: angiopoietin 2
  • Interleukin 6 Change From Baseline to 6 h [ Time Frame: baseline and 6 hours ]
    Biological markers of inflammation: interleukin 6
  • Interleukin 6 Change From Baseline to 24 h [ Time Frame: baseline and 24 hours ]
    Biological markers of inflammation: interleukin 6
  • Interleukin 8 Change From Baseline to 6 h [ Time Frame: baseline and 6 hours ]
    Biological markers of inflammation: interleukin 8
  • Interleukin 8 Change From Baseline to 24 h [ Time Frame: baseline and 24 hours ]
    Biological markers of inflammation: interleukin 8
  • RAGE Change From Baseline to 6 h [ Time Frame: baseline and 6 hours ]
    Biological markers of alveolar epithelial injury: receptor for advanced glycation end products (RAGE)
  • RAGE Change From Baseline to 24 h [ Time Frame: baseline and 24 hours ]
    Biological markers of alveolar epithelial injury: receptor for advanced glycation end products (RAGE)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2014)
  • Respiratory efficacy endpoints which include lung injury score, PaO2/FiO2 ratio and oxygenation index at day 3. [ Time Frame: 28 days ]
  • Systemic efficacy endpoints which include SOFA score, ventilator-free days, organ failure free days, mortality, et al. [ Time Frame: 60 days ]
  • Biological efficacy endpoints which includes serial levels of plasma and urine biomarkers. [ Time Frame: 3 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Human Mesenchymal Stromal Cells For Acute Respiratory Distress Syndrome (START)
Official Title  ICMJE 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)
Brief Summary 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).
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Respiratory Distress Syndrome, Adult
Intervention  ICMJE
  • Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells
    Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells was administered intravenously over approximately 60-80 minutes.
  • Biological: Plasma-Lyte A
    Plasma-Lyte A placebo was administered intravenously over approximately 60-80 minutes.
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells
  • Placebo Comparator: Plasma-Lyte A (placebo)
    A single dose of Plasma-Lyte A was administered intravenously over approximately 60-80 minutes.
    Intervention: Biological: Plasma-Lyte A
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 24, 2014)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 9, 2018
Actual Primary Completion Date March 9, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  1. 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)
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
  3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.

Exclusion Criteria:

  1. Age less than 18 years
  2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition of ARDS
  3. Pregnant or breast-feeding
  4. Prisoner
  5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
  6. Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
  7. Moderate to severe liver failure (Childs-Pugh Score > 12)
  8. Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen
  9. 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)
  10. Major trauma in the prior 5 days
  11. Lung transplant patient
  12. No consent/inability to obtain consent
  13. Moribund patient not expected to survive 24 hours
  14. World Health Organization (WHO) Class III or IV pulmonary hypertension
  15. Documented deep venous thrombosis or pulmonary embolism within past 3 months
  16. No arterial line/no intent to place an arterial line
  17. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol
  18. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02097641
Other Study ID Numbers  ICMJE UCSF-hMSC-ARDS-P2
1U01HL108713-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael A. Matthay, University of California, San Francisco
Study Sponsor  ICMJE Michael A. Matthay
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Massachusetts General Hospital
  • Stanford University
  • University of Pittsburgh
  • University of Minnesota
  • Ohio State University
Investigators  ICMJE
Principal Investigator: Michael A Matthay, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP