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

NCT ID: NCT02362646

Last Updated: 2019-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2019-08-23

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.

Detailed Description

Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced heart failure who are treated with left ventricular assist device (LVAD) implantation may result in a renewable source of proliferating functional cardiomyocytes; induce development of capillaries and larger-size blood vessels to supply oxygen and nutrients to endogenous myocardium and newly-implanted cardiomyocytes; and release factors capable of paracrine signaling.

Conditions

Heart Failure; Cardiomyopathy; Ventricular Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MPC Intramyocardial Injection

Intramyocardial injections of 150 million MPCs

Group Type: EXPERIMENTAL

MPC Intramyocardial Injection

Intervention Type: BIOLOGICAL

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

Control Solution

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

Group Type: SHAM_COMPARATOR

Control Solution

Intervention Type: DRUG

Interventions

MPC Intramyocardial Injection

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

Intervention Type: BIOLOGICAL

Control Solution

Intervention Type: DRUG

Other Intervention Names

Mesenchymal Precursor Cell Injection; RevascorTM; 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO; Cryoprotective media

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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)
• Received investigational intervention within 30 days prior to randomization
• Treatment and/or an incomplete follow-up treatment of any investigational cell based therapy within 6 months prior to randomization
• Active participation in other research therapy for cardiovascular repair/regeneration
• Prior recipient of stem precursor cell therapy for cardiac repair
• Pregnant or breastfeeding at time of randomization.
• History of known or suspected hypercoagulable state in the opinion of the investigator

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Annetine Gelijns

OTHER

Sponsor Role: lead

Responsible Party

Annetine Gelijns

Chair, Department of Population Health Science & Policy; Edmond A. Guggenheim Professor of Health Policy; Co-Director, InCHOIR

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Patrick O'Gara, MD

Role: STUDY_CHAIR

Brigham and Women's Hospital

Richard Weisel, MD

Role: STUDY_CHAIR

Toronto General Hospital

Locations

University of Southern California

Los Angeles, California, United States

Stanford University School of Medicine

Stanford, California, United States

University of Maryland

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Einstein Heart Center

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Baylor Research Institute

Plano, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Virginia Health Systems

Charlottesville, Virginia, United States

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

University of Alberta Hospital

Edmonton, Alberta, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Institut Universitaire de Cardiologie de Quebec (Hopital Laval)

Québec, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 30912838 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.ctsurgerynet.org/

Cardiothoracic Surgical Network Website

Other Identifiers

2U01HL088942-07

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 08-1078-0008

Identifier Type: -

Identifier Source: org_study_id