Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients

NCT02362646 | Completed Phase 2 Results DMC

• 2 other identifiers: GCO 08-1078-00082U01HL088942-07
• Study Type: interventional
• Target: 159
• Locations: 2 countries
• Sites: 19

Brief Summary

The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.

Conditions

Heart Failure; Cardiomyopathy; Ventricular Dysfunction

Keywords

Heart Failure; Left Ventricular Assist Device; Heart Transplantation; Cardiomyopathy, Destination Therapy; Cell Therapy; Bridge to Transplant

Outcome Measures

Primary Outcomes (2)

• Number of Temporary Weans From LVAD Support Tolerated

  functional status, defined by the number of temporary weans from LVAD support tolerated over the 6 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt.

  up to 6 months

• Number of Participants With Adverse Events

  Safety as assessed by number of study intervention-related adverse events

  up to 6 months

Secondary Outcomes (14)

• Physiologic Assessments

  up to 12 months

• Histopathological Assessments of Myocardial Tissue

  up to 12 months

• Overall Survival

  up to 12 months

• Change in Quality of Life (QoL)

  6 months and 12 months

• Hopkins Verbal Learning Test

  3 months and 12 months

Study Arms (2)

MPC Intramyocardial Injection

EXPERIMENTAL

Intramyocardial injections of 150 million MPCs

Biological: MPC Intramyocardial Injection

Control Solution

SHAM COMPARATOR

Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO

Drug: Control Solution

Interventions

MPC Intramyocardial Injection BIOLOGICAL

Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation

Also known as: Mesenchymal Precursor Cell Injection, RevascorTM

MPC Intramyocardial Injection

Control Solution DRUG

Also known as: 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO, Cryoprotective media

Control Solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation
• Age 18 years or older
• If the subject or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after procedure
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening
• Admitted to the clinical center at the time of randomization
• Clinical indication and accepted candidate for implantation of an FDA-approved (US sites only) or Health Canada-approved (Canadian sites only) implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.

You may not qualify if:

• Planned percutaneous LVAD implantation
• Anticipated requirement for biventricular mechanical support
• Concomitant arrhythmia ablation at time of LVAD implantation
• \-- Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation
• Cardiothoracic surgery within 30 days prior to randomization
• Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as unstable plaque rupture, erosion or dissection within 30 days prior to randomization
• Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty
• Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism)
• Stroke within 30 days prior to randomization
• Platelet count \< 100,000/ul within 24 hours prior to randomization
• Acute infectious process: acute bacterial, fungal, or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis
• Presence of \>10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens
• A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products
• History of a known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated
• Presence of human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Annetine Gelijns: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (19)

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Einstein Heart Center

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor Research Institute

Plano, Texas, 75093, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Virginia Health Systems

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53726, United States

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Institut Universitaire de Cardiologie de Quebec (Hopital Laval)

Québec, Quebec, G1V 4G5, Canada

Location

Related Publications (1)

• Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, Acker MA, Selzman CH, Soltesz EG, Kern JA, Maltais S, Charbonneau E, Pan S, Marks ME, Moquete EG, O'Sullivan KL, Taddei-Peters WC, McGowan LK, Green C, Rose EA, Jeffries N, Parides MK, Weisel RD, Miller MA, Hung J, O'Gara PT, Moskowitz AJ, Gelijns AC, Bagiella E, Milano CA; Cardiothoracic Surgical Trials Network. Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial. JAMA. 2019 Mar 26;321(12):1176-1186. doi: 10.1001/jama.2019.2341.

  PMID: 30912838 DERIVED

Related Links

• Cardiothoracic Surgical Network Website

MeSH Terms

Conditions

Heart Failure; Cardiomyopathies; Ventricular Dysfunction

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Annetine Gelijns, PhD
• Organization: Icahn School of Medicine at Mount Sinai

annetine.gelijns@mssm.edu

212-659-9567

Study Officials

• Patrick O'Gara, MD

  Brigham and Women's Hospital

  STUDY CHAIR

• Richard Weisel, MD

  Toronto General Hospital

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair, Department of Population Health Science & Policy; Edmond A. Guggenheim Professor of Health Policy; Co-Director, InCHOIR

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: February 13, 2015
• Study Start: July 1, 2015
• Primary Completion: August 10, 2018
• Study Completion: August 23, 2019
• Last Updated: November 26, 2019
• Results First Posted: November 26, 2019

Record last verified: 2019-11

Locations

US (16); CA (3)