Back to resultsSafety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Primary Purpose
Heart Failure, Cardiomyopathy, Ventricular Dysfunction
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MPC Intramyocardial Injection
Control Solution
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Left Ventricular Assist Device, Heart Transplantation, Cardiomyopathy, Destination Therapy, Cell Therapy, Bridge to Transplant
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
Sites / Locations
- University of Southern California
- Stanford University School of Medicine
- University of Maryland
- University of Michigan
- Henry Ford Hospital
- Montefiore Einstein Heart Center
- Columbia University Medical Center
- Duke University
- Cleveland Clinic Foundation
- Ohio State University
- University of Pennsylvania
- University of Pittsburgh
- Baylor Research Institute
- University of Utah
- University of Virginia Health Systems
- University of Wisconsin School of Medicine and Public Health
- University of Alberta Hospital
- Toronto General Hospital
- Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
MPC Intramyocardial Injection
Control Solution
Arm Description
Intramyocardial injections of 150 million MPCs
Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
Outcomes
Primary Outcome Measures
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.
Number of Participants With Adverse Events
Safety as assessed by number of study intervention-related adverse events
Secondary Outcome Measures
Physiologic Assessments
Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes)
Histopathological Assessments of Myocardial Tissue
Overall Survival
Change in Quality of Life (QoL)
Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure.
Hopkins Verbal Learning Test
Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Trailmaking Tests A and B
Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
MCG Complex Figures
Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Digit Span
Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Digit Symbol Substitution Test
Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Controlled Oral Word Association
Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Length of Stay
Length of stay of index hospitalization
Hospitalizations
Frequency and cause of readmissions
Hospital Costs
Hospital resource use
Functional Status
functional status, defined by the number of temporary weans from LVAD support tolerated
Full Information
NCT ID
NCT02362646
First Posted
February 9, 2015
Last Updated
November 7, 2019
Sponsor
Annetine Gelijns
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT02362646
Brief Title
Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Official Title
Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
August 10, 2018 (Actual)
Study Completion Date
August 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Annetine Gelijns
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Cardiomyopathy, Ventricular Dysfunction
Keywords
Heart Failure, Left Ventricular Assist Device, Heart Transplantation, Cardiomyopathy, Destination Therapy, Cell Therapy, Bridge to Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
159 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MPC Intramyocardial Injection
Arm Type
Experimental
Arm Description
Intramyocardial injections of 150 million MPCs
Arm Title
Control Solution
Arm Type
Sham Comparator
Arm Description
Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
Intervention Type
Biological
Intervention Name(s)
MPC Intramyocardial Injection
Other Intervention Name(s)
Mesenchymal Precursor Cell Injection, RevascorTM
Intervention Description
Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation
Intervention Type
Drug
Intervention Name(s)
Control Solution
Other Intervention Name(s)
50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO, Cryoprotective media
Primary Outcome Measure Information:
Title
Number of Temporary Weans From LVAD Support Tolerated
Description
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.
Time Frame
up to 6 months
Title
Number of Participants With Adverse Events
Description
Safety as assessed by number of study intervention-related adverse events
Time Frame
up to 6 months
Secondary Outcome Measure Information:
Title
Physiologic Assessments
Description
Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes)
Time Frame
up to 12 months
Title
Histopathological Assessments of Myocardial Tissue
Time Frame
up to 12 months
Title
Overall Survival
Time Frame
up to 12 months
Title
Change in Quality of Life (QoL)
Description
Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure.
Time Frame
6 months and 12 months
Title
Hopkins Verbal Learning Test
Description
Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Time Frame
3 months and 12 months
Title
Trailmaking Tests A and B
Description
Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Time Frame
3 months and 12 months
Title
MCG Complex Figures
Description
Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Time Frame
3 months and 12 months
Title
Digit Span
Description
Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Time Frame
3 months and 12 months
Title
Digit Symbol Substitution Test
Description
Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Time Frame
3 months and 12 months
Title
Controlled Oral Word Association
Description
Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel.
Time Frame
3 months and 12 months
Title
Length of Stay
Description
Length of stay of index hospitalization
Time Frame
up to 12 months
Title
Hospitalizations
Description
Frequency and cause of readmissions
Time Frame
up to 12 months
Title
Hospital Costs
Description
Hospital resource use
Time Frame
up to 12 months
Title
Functional Status
Description
functional status, defined by the number of temporary weans from LVAD support tolerated
Time Frame
up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick O'Gara, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Richard Weisel, MD
Organizational Affiliation
Toronto General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Montefiore Einstein Heart Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Baylor Research Institute
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
University of Virginia Health Systems
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
University of Wisconsin School of Medicine and Public Health
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53726
Country
United States
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Institut Universitaire de Cardiologie de Quebec (Hopital Laval)
City
Québec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
30912838
Citation
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. Erratum In: JAMA. 2019 Sep 3;322(9):895.
Results Reference
derived
Links:
URL
http://www.ctsurgerynet.org/
Description
Cardiothoracic Surgical Network Website
Learn more about this trial
Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
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