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

March 18, 2019 updated by: Michael A. Matthay

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)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California San Francisco
      • Stanford, California, United States, 94305
        • Stanford University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Minnesota
      • Saint Paul, Minnesota, United States, 55108
        • University Of Minnesota Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
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.
Placebo Comparator: Plasma-Lyte A (placebo)
A single dose of Plasma-Lyte A was administered intravenously over approximately 60-80 minutes.
Biological: Plasma-Lyte A
Plasma-Lyte A placebo was administered intravenously over approximately 60-80 minutes.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
6 hours
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
24 hours
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
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PaO2:FiO2 Change From Baseline to Day 3
Time Frame: baseline and day 3
Efficacy endpoint: PaO2:FiO2 change from baseline to day 3
baseline and 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.
baseline and day 3
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
baseline and day 2
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.
baseline and day 3
Number of Patients Death to Day 28
Time Frame: 28 days
Efficacy endpoint: all-cause mortality at day 28
28 days
Mortality to Day 60
Time Frame: 60 days
Efficacy endpoint: all-cause mortality at day 60
60 days
Number of Ventilator-free Days to Day 28
Time Frame: 28 days
Efficacy endpoint: Number of ventilator-free days to day 28.
28 days
Non-pulmonary Organ-failure-free Days to Day 28
Time Frame: 28 days
Efficacy endpoint: Non-pulmonary organ-failure-free days to day 28
28 days
Angiopoietin 2 Change From Baseline to 6 h
Time Frame: baseline and 6 hours
Biological markers of endothelial injury: angiopoietin 2
baseline and 6 hours
Angiopoietin 2 Change From Baseline to 24 h
Time Frame: baseline and 24 hours
Biological markers of endothelial injury: angiopoietin 2
baseline and 24 hours
Interleukin 6 Change From Baseline to 6 h
Time Frame: baseline and 6 hours
Biological markers of inflammation: interleukin 6
baseline and 6 hours
Interleukin 6 Change From Baseline to 24 h
Time Frame: baseline and 24 hours
Biological markers of inflammation: interleukin 6
baseline and 24 hours
Interleukin 8 Change From Baseline to 6 h
Time Frame: baseline and 6 hours
Biological markers of inflammation: interleukin 8
baseline and 6 hours
Interleukin 8 Change From Baseline to 24 h
Time Frame: baseline and 24 hours
Biological markers of inflammation: interleukin 8
baseline and 24 hours
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)
baseline and 6 hours
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)
baseline and 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Michael A. Matthay

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
University of Pittsburgh
Stanford University
Ohio State University
University of Minnesota

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael A Matthay, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 9, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 9, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 19, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 10, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UCSF-hMSC-ARDS-P2
  • 1U01HL108713-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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