NCT02097641

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Mar 2014

Typical duration for phase_2

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 15, 2014

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

March 19, 2014

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 27, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 9, 2017

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 9, 2018

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

April 10, 2019

Completed
Last Updated

April 10, 2019

Status Verified

March 1, 2019

Enrollment Period

3 years

First QC Date

March 19, 2014

Results QC Date

January 15, 2019

Last Update Submit

March 18, 2019

Conditions

Respiratory Distress Syndrome, Adult

Keywords

Allogeneic Bone Marrow-derived Human Mesenchymal Stromal CellsAcute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (3)

  • Numbers of Patients Occurred Pre-specified Infusion Associated Events Occurring Within 6 Hours of Study Infusion

    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

    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)

    Safety endpoint: Any unexpected severe adverse events in two groups

    12 months

Secondary Outcomes (16)

  • PaO2:FiO2 Change From Baseline to Day 3

    baseline and day 3

  • Lung Injury Score From Baseline to Day 3

    baseline and day 3

  • Oxygenation Index Change From Baseline to Day 2

    baseline and day 2

  • SOFA Score Change From Baseline to Day 3

    baseline and day 3

  • Number of Patients Death to Day 28

    28 days

  • +11 more secondary outcomes

Study Arms (2)

Human Mesenchymal Stromal Cells (hMSCs)

EXPERIMENTAL

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

Plasma-Lyte A (placebo)

PLACEBO COMPARATOR

A single dose of Plasma-Lyte A was administered intravenously over approximately 60-80 minutes.

Biological: Plasma-Lyte A

Interventions

Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal CellsBIOLOGICAL

Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells was administered intravenously over approximately 60-80 minutes.

Human Mesenchymal Stromal Cells (hMSCs)
Plasma-Lyte ABIOLOGICAL

Plasma-Lyte A placebo was administered intravenously over approximately 60-80 minutes.

Plasma-Lyte A (placebo)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • World Health Organization (WHO) Class III or IV pulmonary hypertension
  • Documented deep venous thrombosis or pulmonary embolism within past 3 months
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota Medical Center

Saint Paul, Minnesota, 55108, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (4)

  • Matthay MA, Calfee CS, Zhuo H, Thompson BT, Wilson JG, Levitt JE, Rogers AJ, Gotts JE, Wiener-Kronish JP, Bajwa EK, Donahoe MP, McVerry BJ, Ortiz LA, Exline M, Christman JW, Abbott J, Delucchi KL, Caballero L, McMillan M, McKenna DH, Liu KD. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med. 2019 Feb;7(2):154-162. doi: 10.1016/S2213-2600(18)30418-1. Epub 2018 Nov 16.

    PMID: 30455077RESULT

  • Wick KD, Leligdowicz A, Zhuo H, Ware LB, Matthay MA. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight. 2021 Jun 22;6(12):e148983. doi: 10.1172/jci.insight.148983.

    PMID: 33974564DERIVED

  • 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.

    PMID: 25593740DERIVED

  • 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.

    PMID: 24891325DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Plasmalyte A

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration Disorders

Results Point of Contact

Title
Michael A. Matthay, MD
Organization
University of California San Francisco
michael.matthay@ucsf.edu
415-502-7434

Study Officials

  • Michael A Matthay, MD

    University of California, San Francisco

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

March 19, 2014

First Posted

March 27, 2014

Study Start

March 15, 2014

Primary Completion

March 9, 2017

Study Completion

February 9, 2018

Last Updated

April 10, 2019

Results First Posted

April 10, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will not share

Locations

US(6)