Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome

NCT01775774 | Completed Phase 1 Results DMC

• 2 other identifiers: ARDS MSC 0011U01HL108713-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

Acute Respiratory Distress Syndrome; Acute Lung Injury; Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

Outcome Measures

Primary Outcomes (1)

• 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

  24 hours

Secondary Outcomes (6)

• 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.

• Ventilator Free Days at Study Day 28

  time of initiating unassisted breathing to day 28

• Duration of Vasopressor Use (Days)

  28 days

• ICU Free Days to Day 28

  28 days after study enrollment

• Hospital Survival to Day 60

  60 days after randomization

Study Arms (1)

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

EXPERIMENTAL

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.

Biological: Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

Interventions

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells BIOLOGICAL

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells will be administered intravenously.

Allogeneic Bone Marrow-Derived Human Mesenchymal Stem Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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
• WHO Class III or IV pulmonary hypertension
• Documented deep venous thrombosis or pulmonary embolism within past 3 months

Sponsors & Collaborators

• Michael A. Matthay: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Massachusetts General Hospital: collaborator
• Stanford University: collaborator
• University of Pittsburgh: collaborator
• University of Minnesota: collaborator

Study Sites (4)

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• 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.

  PMID: 25529339 RESULT

• 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: 25593740 DERIVED

• 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: 24891325 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Acute Lung Injury

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury

Results Point of Contact

• Title: Michael A. Matthay, MD
• Organization: University of California San Francisco

michael.matthay@ucsf.edu

415-353-1206

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prinicpal Investigator

Study Record Dates

• First Submitted: January 18, 2013
• First Posted: January 25, 2013
• Study Start: July 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2015
• Last Updated: August 14, 2017
• Results First Posted: August 14, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)