Ischemic CardiomyopathyPhase 2CONCERT-HFNCT02501811

Combination of Mesenchymal and C-kit+ Cardiac Stem Cells as Regenerative Therapy for Heart Failure

A Phase 2 study testing Mesenchymal Stem Cells (MSC) and c-kit+ cells in people with Ischemic Cardiomyopathy, run by The University of Texas Health Science Center, Houston at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a phase II, randomized, placebo-controlled clinical trial designed to assess feasibility, safety, and effect of autologous bone marrow-derived mesenchymal stem cells (MSCs) and c-kit+ cells both alone and in combination (Combo), compared to placebo (cell-free Plasmalyte-A medium) as well as each other… Read more about this study

Who is it for?: Ages 21 to 79 years
Conditions the study is for: Ischemic Cardiomyopathy
What is being tested?: Mesenchymal Stem Cells (MSC) and c-kit+ cells
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 125 participants
Where: 7 sitesUnited States
Study dates: Oct 2015to 22 Jul 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Be ≥ 21 and <80 years of age
Have documented coronary artery disease (CAD) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF
Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by cMRI
Have an EF ≤ 40% by cMRI
Be receiving guideline-driven medical therapy for heart failure at stable and tolerated doses for ≥ 1 month prior to consent. For beta-blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.
Be a candidate for cardiac catheterization
Have NYHA class I, II, or III heart failure symptoms
If a female of childbearing potential, be willing to use one form of birth control for the duration of the study, and undergo a pregnancy test at baseline and within 36 hours prior to injection

Who cannot join

Indication for standard-of-care surgery (including valve surgery, placement of left-ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 4 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS status 1A or 1B, and they must have documented low probability of being transplanted
Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe (any valve) insufficiency/regurgitation within 12 months of consent
Aortic stenosis with valve area ≤ 1.5 cm2
History of ischemic or hemorrhagic stroke within 90 days of consent
History of a left ventricular remodeling surgical procedure utilizing prosthetic material
Presence of a pacemaker and/or implantable cardioverter-defibrillator (ICD) generator with any of the following limitations/conditions:

Show all 36Show fewer

manufactured before the year 2000
leads implanted < 6 weeks prior to consent
non-transvenous epicardial, or abandoned leads
subcutaneous ICDs
leadless pacemakers
any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated
Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded)
A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent
Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
Presence of LV thrombus
Evidence of active myocarditis
Baseline maximal oxygen consumption (VO2 max) greater than 75% of age and gender based predictive values
Baseline eGFR <35 ml/min/1.73m2
Blood glucose levels (HbA1c) >10%
Hematologic abnormality evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet count < 100,000/ul
Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the upper limit of normal (ULN)
Coagulopathy (INR ≥ 1.3) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors). Subjects who cannot be withdrawn from anticoagulation will be excluded.
HIV and/or active hepatitis B virus (HBV) or hepatitis C virus (HCV)
Allergy to radiographic contrast material that cannot adequately be managed by premedication
Known history of anaphylactic reaction to penicillin or streptomycin
Received gene or cell-based therapy from any source within the previous 12 months
History of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), excluding basal cell carcinoma and cervical carcinoma in situ which have been definitively treated
Condition that limits lifespan to < 1 year
History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
Participation in an investigational therapeutic or device trial within 30 days of consent
Cognitive or language barriers that prohibit obtaining informed consent or any study elements
Pregnancy or lactation or plans to become pregnant in the next 12 months
Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow-up

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

University of Florida-Department of Medicine
Gainesville, Florida, 32610
Texas Heart Institute
Houston, Texas, 77030
Indiana Center for Vascular Biology and Medicine
Indianapolis, Indiana, 46202
University of Louisville
Louisville, Kentucky, 40202
University of Miami-Interdisciplinary Stem Cell Institute
Miami, Florida, 33101
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, 55407
Stanford University School of Medicine (Falk Cardiovascular Research Center)
Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase II, Randomized, Placebo-Controlled Study of the Safety, Feasibility, & Efficacy of Autologous Mesenchymal Stem Cells & C-kit+ Cardiac Stem Cells, Alone or in Combination, Administered Transendocardially in Subjects With Ischemic HF

Read the detailed description

This is a randomized, placebo-controlled clinical trial designed to evaluate the feasibility, safety, and effect of Combo, MSCs alone, and c-kit+ cells alone compared with placebo as well as each other in subjects with heart failure of ischemic etiology. Following a successful lead-in phase, a total of one hundred forty-four (144) subjects will be randomized (1:1:1:1) to receive Combo, MSCs, c-kit+ cells, or placebo. After randomization, baseline imaging, relevant harvest procedures, and study product injection, subjects will be followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post study product injection. All subjects will receive study product injection (cells or placebo) using the NOGA® XP Mapping and Navigation System. Subjects will have delayed-enhanced magnetic resonance imaging (DEMRI) scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints will be assessed at the 6 and 12 month visits which will occur 180 ±30 days and 365 ±30 days respectively from the day of study product injection (Day 0). For the purpose of the endpoint analysis and safety evaluations, the Investigators will utilize an "intention-to-treat" study population, however an as treated analysis will also be conducted.

Conditions: Ischemic Cardiomyopathy
Being tested: Mesenchymal Stem Cells (MSC), c-kit+ cells, Placebo (Plasmalyte A)
Keywords: Heart Failure, Ischemia, Autologous Stem Cells, LV dysfunction, Mesenchymal Stem Cells, c-kit+ Cells, Combination Cell Therapy, LV function, Functional status
Medical subject headings: Heart Failure, Ischemia, Ventricular Dysfunction, Left

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Mesenchymal Stem Cells (MSC)Biological
15 transendocardial injections of 0.4ml MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
c-kit+ cellsBiological
15 transendocardial injections of 0.4ml c-kit+ cells administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Placebo (Plasmalyte A)Biological
Also called Plasmalyte A
15 transendocardial injections of 0.4ml placebo administered to the left ventricle via NOGA Myostar injection catheter (single procedure)

Study groups in NCT02501811
Study group	Role	What they receive
Mesenchymal Stem Cells (MSC)	Experimental	Target dose of 150 million MSCs Receives: Biological: Mesenchymal Stem Cells (MSC)
c-kit+ cells	Experimental	Target dose of 5 million c-kit+ cells Receives: Biological: c-kit+ cells
Combination Cells (MSC and c-kit+ cells)	Experimental	Target dose of 150 million MSCs and 5 million c-kit+ cells Receives: Biological: Mesenchymal Stem Cells (MSC); Biological: c-kit+ cells
Placebo (Plasmalyte A)	Placebo comparator	Plasmalyte A Receives: Biological: Placebo (Plasmalyte A)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Change in left ventricular ejection fraction as assessed via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Global Strain (HARP MRI)
Change in global circumferential strain as assessed via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Regional Strain (HARP MRI)
Change in regional longitudinal strain as assessed via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)
Change in left ventricular end diastolic volume index as measured via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)
Change in left ventricular end systolic volume index as assessed via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Left Ventricular Sphericity Index
Change in left ventricular sphericity as assessed via cardiac MRI. Sphericity index is the ratio of the long and short axis measurements of the left ventricle.
Measured: Baseline to 6 months
Change From Baseline in Scar Size Percent (DEMRI)
Change in scar size percent as assessed via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Scar Tissue Mass (DEMRI)
Change in scar tissue mass as assessed via cardiac MRI
Measured: Baseline to 6 months
Change From Baseline in Maximal Oxygen Consumption (Peak VO2)
Change in maximal oxygen consumption (peak V02) as assessed via treadmill
Measured: Baseline to 6 months
Change From Baseline in Exercise Tolerance (Six Minute Walk Test)
Change in distance walked (in meters) as measured by the 6 minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 minutes). The average distance of the two walk tests was used for analysis.
Measured: Baseline to 6 months
Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score
Change in the quality of life summary score as measured by the Minnesota Living with Heart Failure Questionnaire. Minimum and maximum scores for the scale are 0 and 105 respectively. Lower scores indicative of better outcomes.
Measured: Baseline to 6 months
Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw
Measured: Baseline to 6 months
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Global Strain (HARP MRI)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Regional Strain (HARP MRI)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, 12 months)
Change From Baseline in Left Ventricular Sphericity Index-Trajectory
Sphericity index is the ratio of the long and short axis measurements of the left ventricle. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Scar Size Percent (DEMRI)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Maximal Oxygen Consumption (Peak VO2)-Trajectory
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory
Two walk tests were completed at each endpoint visit (separated by 30 minutes). The average distance of the two walk tests was used for analysis. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score-Trajectory
Minimum and maximum scores for the scale are 0 and 105 respectively. Lower scores indicative of better outcomes. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The 2nd and 3rd set of results represent differences for varying slopes from the interaction model.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory
Log transformation used. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Measured: Assessed as a trajectory (baseline, 6 months, and 12 months)
Participants With Major Adverse Cardiac Events (MACE)
Number of participants with adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).
Measured: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Participants Experiencing Other Significant Clinical Events
Number of participants experiencing other significant adjudicated clinical events including: non-fatal stroke, non-fatal MI, coronary artery revascularization, ventricular tachycardia/fibrillation, and pericardial tamponade
Measured: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Cumulative Days Alive and Out of Hospital for Heart Failure
Days alive and out of hospital during the study evaluation period. Subjects were allotted a visit window extending 30 days past their anticipated 12-month visit. Some participants had extended 12-month visit windows due to the COVID-19 pandemic.
Measured: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201522 Jul 2020

First posted17 Jul 2015 (estimated)
Study startOct 2015
Primary completion25 Jun 2020
Study completion22 Jul 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Ischemic CardiomyopathyStudies of the same condition, open and under way.
More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 125 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02501811
Sponsor's protocol ID: HSC-SPH-15-0413
Other IDs: 5UM1HL087318
Acronym: CONCERT-HF
Status last verified: Mar 2021
First submitted: 15 Jul 2015
Last updated: 26 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Hare JM, Bolli R, Cooke JP, Gordon DJ, Henry TD, Perin EC, March KL, Murphy MP, Pepine CJ, Simari RD, Skarlatos SI, Traverse JH, Willerson JT, Szady AD, Taylor DA, Vojvodic RW, Yang PC, Moye LA; Cardiovascular Cell Therapy Research Network. Phase II clinical research design in cardiology: learning the right lessons too well: observations and recommendations from the Cardiovascular Cell Therapy Research Network (CCTRN). Circulation. 2013 Apr 16;127(15):1630-5. doi: 10.1161/CIRCULATIONAHA.112.000779. No abstract available.
PubMed 23588961
Nazarian S, Halperin HR. How to perform magnetic resonance imaging on patients with implantable cardiac arrhythmia devices. Heart Rhythm. 2009 Jan;6(1):138-43. doi: 10.1016/j.hrthm.2008.10.021. Epub 2008 Oct 22. No abstract available.
PubMed 19121814
Bolli R, Hare JM, March KL, Pepine CJ, Willerson JT, Perin EC, Yang PC, Henry TD, Traverse JH, Mitrani RD, Khan A, Hernandez-Schulman I, Taylor DA, DiFede DL, Lima JAC, Chugh A, Loughran J, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Moye L, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit+ Cardiac Stem Cells As Regenerative Therapy for Heart Failure). Circ Res. 2018 Jun 8;122(12):1703-1715. doi: 10.1161/CIRCRESAHA.118.312978. Epub 2018 Apr 27.
PubMed 29703749
Chacon-Alberty L, Tan X, Li M, Tang XL, Hochman-Mendez C, Bolli R. Changes in Circulating Biomarkers in Patients With Ischemic Heart Failure After Treatment With Autologous Mesenchymal Stromal Cells and c-Kit-Positive Cardiac Cells, Alone or in Combination: Results From the Cardiovascular Cell Therapy Research Network CONCERT-HF Clinical Trial. J Am Heart Assoc. 2026 May 5;15(9):e045963. doi: 10.1161/JAHA.125.045963. Epub 2026 Apr 20.
PubMed 42003602
Kato Y, Kizer JR, Ostovaneh MR, Lazar J, Peng Q, van der Geest RJ, Lima JAC, Ambale-Venkatesh B. Extracellular volume-guided late gadolinium enhancement analysis for non-ischemic cardiomyopathy: The Women's Interagency HIV Study. BMC Med Imaging. 2021 Jul 27;21(1):116. doi: 10.1186/s12880-021-00649-6.
PubMed 34315432

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Ischemic Cardiomyopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Randomized, Placebo-Controlled Study of the Safety, Feasibility, & Efficacy of Autologous Mesenchymal Stem Cells & C-kit+ Cardiac Stem Cells, Alone or in Combination, Administered Transendocardially in Subjects With Ischemic HF
ClinicalTrials.gov ID: NCT02501811
Acronym / sponsor ID: CONCERT-HF / HSC-SPH-15-0413
Conditions: Ischemic Cardiomyopathy
Keywords: Heart Failure, Ischemia, Autologous Stem Cells, LV dysfunction, Mesenchymal Stem Cells, c-kit+ Cells, Combination Cell Therapy, LV function
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 125 participants (actual)
Lead sponsor: The University of Texas Health Science Center, HoustonUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Oct 2015
Primary completion: 25 Jun 2020 (actual)
Study completion: 22 Jul 2020 (actual)
First posted: 17 Jul 2015 (estimated)
Results: Posted 26 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Mesenchymal Stem Cells (MSC)	Experimental	Biological: Mesenchymal Stem Cells (MSC)Target dose of 150 million MSCs
c-kit+ cells	Experimental	Biological: c-kit+ cellsTarget dose of 5 million c-kit+ cells
Combination Cells (MSC and c-kit+ cells)	Experimental	Biological: Mesenchymal Stem Cells (MSC), Biological: c-kit+ cellsTarget dose of 150 million MSCs and 5 million c-kit+ cells
Placebo (Plasmalyte A)	Placebo comparator	Biological: Placebo (Plasmalyte A)Plasmalyte A

Who may qualify

Ages: 21 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Be ≥ 21 and <80 years of age
Have documented coronary artery disease (CAD) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF
Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by cMRI
Have an EF ≤ 40% by cMRI
Be receiving guideline-driven medical therapy for heart failure at stable and tolerated doses for ≥ 1 month prior to consent. For beta-blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.

Key exclusion criteria (36 listed)

Indication for standard-of-care surgery (including valve surgery, placement of left-ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 4 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS status 1A or 1B, and they must have documented low probability of being transplanted
Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe (any valve) insufficiency/regurgitation within 12 months of consent
Aortic stenosis with valve area ≤ 1.5 cm2
History of ischemic or hemorrhagic stroke within 90 days of consent
History of a left ventricular remodeling surgical procedure utilizing prosthetic material

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Mesenchymal Stem Cells (MSC)15 transendocardial injections of 0.4ml MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)	Biological	Combination Cells (MSC and c-kit+ cells), Mesenchymal Stem Cells (MSC)
c-kit+ cells15 transendocardial injections of 0.4ml c-kit+ cells administered to the left ventricle via NOGA Myostar injection catheter (single procedure)	Biological	Combination Cells (MSC and c-kit+ cells), c-kit+ cells
Placebo (Plasmalyte A)Also: Plasmalyte A15 transendocardial injections of 0.4ml placebo administered to the left ventricle via NOGA Myostar injection catheter (single procedure)	Biological	Placebo (Plasmalyte A)

Primary outcome

Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline to 6 months
Change in left ventricular ejection fraction as assessed via cardiac MRI
Change From Baseline in Global Strain (HARP MRI)
Time frame: Baseline to 6 months
Change in global circumferential strain as assessed via cardiac MRI
Change From Baseline in Regional Strain (HARP MRI)
Time frame: Baseline to 6 months
Change in regional longitudinal strain as assessed via cardiac MRI
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)
Time frame: Baseline to 6 months
Change in left ventricular end diastolic volume index as measured via cardiac MRI
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)
Time frame: Baseline to 6 months
Change in left ventricular end systolic volume index as assessed via cardiac MRI
Change From Baseline in Left Ventricular Sphericity Index
Time frame: Baseline to 6 months
Change in left ventricular sphericity as assessed via cardiac MRI. Sphericity index is the ratio of the long and short axis measurements of the left ventricle.
Change From Baseline in Scar Size Percent (DEMRI)
Time frame: Baseline to 6 months
Change in scar size percent as assessed via cardiac MRI
Change From Baseline in Scar Tissue Mass (DEMRI)
Time frame: Baseline to 6 months
Change in scar tissue mass as assessed via cardiac MRI
Change From Baseline in Maximal Oxygen Consumption (Peak VO2)
Time frame: Baseline to 6 months
Change in maximal oxygen consumption (peak V02) as assessed via treadmill
Change From Baseline in Exercise Tolerance (Six Minute Walk Test)
Time frame: Baseline to 6 months
Change in distance walked (in meters) as measured by the 6 minute walk test. Two walk tests were completed at each endpoint visit (separated by 30 minutes). The average distance of the two walk tests was used for analysis.
Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score
Time frame: Baseline to 6 months
Change in the quality of life summary score as measured by the Minnesota Living with Heart Failure Questionnaire. Minimum and maximum scores for the scale are 0 and 105 respectively. Lower scores indicative of better outcomes.
Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
Time frame: Baseline to 6 months
Change in N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) as measured via laboratory blood draw
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Global Strain (HARP MRI)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Regional Strain (HARP MRI)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Left Ventricular Sphericity Index-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Sphericity index is the ratio of the long and short axis measurements of the left ventricle. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Scar Size Percent (DEMRI)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Maximal Oxygen Consumption (Peak VO2)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Two walk tests were completed at each endpoint visit (separated by 30 minutes). The average distance of the two walk tests was used for analysis. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Minimum and maximum scores for the scale are 0 and 105 respectively. Lower scores indicative of better outcomes. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The 2nd and 3rd set of results represent differences for varying slopes from the interaction model.
Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Log transformation used. The change in this measure over time is assessed using a repeated measures linear regression model of trajectory (change over time). The first set of results reflects the model within each arm and represents change per 6 months within that treatment arm. The second set of results reflects an overall model with all patients and the results represent the change per 6 months irrespective of treatment arm.
Participants With Major Adverse Cardiac Events (MACE)
Time frame: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Number of participants with adjudicated events including death, hospitalization for worsening heart failure, and/or other exacerbation of heart failure (non-hospitalization).
Participants Experiencing Other Significant Clinical Events
Time frame: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Number of participants experiencing other significant adjudicated clinical events including: non-fatal stroke, non-fatal MI, coronary artery revascularization, ventricular tachycardia/fibrillation, and pericardial tamponade
Cumulative Days Alive and Out of Hospital for Heart Failure
Time frame: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Days alive and out of hospital during the study evaluation period. Subjects were allotted a visit window extending 30 days past their anticipated 12-month visit. Some participants had extended 12-month visit windows due to the COVID-19 pandemic.

Results and safety

Results posted to the registry on 26 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MSCs + CPCs	33	29
MSCs	29	23
CPCs	31	25
Placebo	32	25

Primary outcome: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

Time frame: Baseline to 6 months. Mean (Standard Deviation). Unit: percentage of end diastolic volume

Measure	MSCs + CPCs n = 28	MSCs n = 24	CPCs n = 25	Placebo n = 25
Value	-0.42 (3.90)	0.37 (2.95)	1.05 (3.68)	-0.33 (3.73)

MSCs + CPCs vs Placebo: Mean Difference (Final Values): -0.08 (95% CI -2.190 to 2.023), p = 0.993, ANCOVA
MSCs vs Placebo: Mean Difference (Final Values): 0.70 (95% CI -1.229 to 2.635), p = 0.499, ANCOVA
CPCs vs Placebo: Mean Difference (Final Values): 1.38 (95% CI -0.729 to 3.485), p = 0.578, ANCOVA

Population analysed: Participants with available analyzable LVEF at baseline and 6 months

Primary outcome: Change From Baseline in Global Strain (HARP MRI)

Time frame: Baseline to 6 months. Mean (Standard Deviation). Unit: percent

Measure	MSCs + CPCs n = 26	MSCs n = 17	CPCs n = 22	Placebo n = 16
Value	-0.36 (3.20)	0.48 (3.36)	0.56 (2.08)	-0.10 (3.38)

MSCs + CPCs vs Placebo: Mean Difference (Final Values): -0.26 (95% CI -2.406 to 1.887), p = 0.942, ANCOVA
MSCs vs Placebo: Mean Difference (Final Values): 0.58 (95% CI -1.815 to 2.975), p = 0.282, ANCOVA
CPCs vs Placebo: Mean Difference (Final Values): 0.66 (95% CI -1.310 to 2.635), p = 0.163, ANCOVA

Population analysed: Participants with available analyzable global circumferential strain at baseline and 6 months.

Primary outcome: Change From Baseline in Regional Strain (HARP MRI)

Time frame: Baseline to 6 months. Mean (Standard Deviation). Unit: percent

Measure	MSCs + CPCs n = 26	MSCs n = 18	CPCs n = 22	Placebo n = 17
Value	-0.50 (2.33)	-0.51 (2.33)	-0.76 (2.49)	-0.91 (2.44)

MSCs + CPCs vs Placebo: Mean Difference (Final Values): 0.40 (95% CI -1.118 to 1.927), p = 0.733, ANCOVA
MSCs vs Placebo: Mean Difference (Final Values): 0.40 (95% CI -1.248 to 2.041), p = 0.735, ANCOVA
CPCs vs Placebo: Mean Difference (Final Values): 0.15 (95% CI -1.464 to 1.767), p = 0.794, ANCOVA

Population analysed: Participants with available analyzable regional longitudinal strain at baseline and 6 months

Primary outcome: Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)

Time frame: Baseline to 6 months. Mean (Standard Deviation). Unit: mL/m^2

Measure	MSCs + CPCs n = 28	MSCs n = 24	CPCs n = 25	Placebo n = 25
Value	0.97 (16.06)	0.21 (11.91)	-1.13 (12.37)	2.99 (11.84)

MSCs + CPCs vs Placebo: Mean Difference (Final Values): -2.02 (95% CI -9.754 to 5.711), p = 0.602, ANCOVA
MSCs vs Placebo: Mean Difference (Final Values): -2.78 (95% CI -9.609 to 4.044), p = 0.443, ANCOVA
CPCs vs Placebo: Mean Difference (Net): -4.13 (95% CI -11.011 to 2.760), p = 0.348, ANCOVA

Population analysed: Participants with available analyzable LVEDVI at baseline and six months

Adverse events

Time frame: Events reported occurred between randomization and the end of 12 Month Visit Window (an average of 395 days following study product injection).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MSCs + CPCs	14 of 33 (42.4%)	10 of 33 (30.3%)	2 of 33
MSCs	14 of 29 (48.3%)	6 of 29 (20.7%)	3 of 29
CPCs	13 of 31 (41.9%)	14 of 31 (45.2%)	2 of 31
Placebo	18 of 32 (56.3%)	15 of 32 (46.9%)	4 of 32

Limitations and caveats (from the sponsor): Relatively small group sizes overall. Relatively long interval between harvest visit and study product injection (approx. 14wks) resulting in patient attrition. Failure of cells to grow from tissue of some patients, resulting in some patients crossing over into other treatment groups.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23588961Hare JM, Bolli R, Cooke JP, Gordon DJ, Henry TD, Perin EC, March KL, Murphy MP, Pepine CJ, Simari RD, Skarlatos SI, Traverse JH, Willerson JT, Szady AD, Taylor DA, Vojvodic RW, Yang PC, Moye LA; Cardiovascular Cell Therapy Research Network. Phase II clinical research design in cardiology: learning the right lessons too well: observations and recommendations from the Cardiovascular Cell Therapy Research Network (CCTRN). Circulation. 2013 Apr 16;127(15):1630-5. doi: 10.1161/CIRCULATIONAHA.112.000779. No abstract available.
Background: PubMed 19121814Nazarian S, Halperin HR. How to perform magnetic resonance imaging on patients with implantable cardiac arrhythmia devices. Heart Rhythm. 2009 Jan;6(1):138-43. doi: 10.1016/j.hrthm.2008.10.021. Epub 2008 Oct 22. No abstract available.
Background: PubMed 29703749Bolli R, Hare JM, March KL, Pepine CJ, Willerson JT, Perin EC, Yang PC, Henry TD, Traverse JH, Mitrani RD, Khan A, Hernandez-Schulman I, Taylor DA, DiFede DL, Lima JAC, Chugh A, Loughran J, Vojvodic RW, Sayre SL, Bettencourt J, Cohen M, Moye L, Ebert RF, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Rationale and Design of the CONCERT-HF Trial (Combination of Mesenchymal and c-kit+ Cardiac Stem Cells As Regenerative Therapy for Heart Failure). Circ Res. 2018 Jun 8;122(12):1703-1715. doi: 10.1161/CIRCRESAHA.118.312978. Epub 2018 Apr 27.
Derived from this study: PubMed 42003602Chacon-Alberty L, Tan X, Li M, Tang XL, Hochman-Mendez C, Bolli R. Changes in Circulating Biomarkers in Patients With Ischemic Heart Failure After Treatment With Autologous Mesenchymal Stromal Cells and c-Kit-Positive Cardiac Cells, Alone or in Combination: Results From the Cardiovascular Cell Therapy Research Network CONCERT-HF Clinical Trial. J Am Heart Assoc. 2026 May 5;15(9):e045963. doi: 10.1161/JAHA.125.045963. Epub 2026 Apr 20.
Derived from this study: PubMed 34315432Kato Y, Kizer JR, Ostovaneh MR, Lazar J, Peng Q, van der Geest RJ, Lima JAC, Ambale-Venkatesh B. Extracellular volume-guided late gadolinium enhancement analysis for non-ischemic cardiomyopathy: The Women's Interagency HIV Study. BMC Med Imaging. 2021 Jul 27;21(1):116. doi: 10.1186/s12880-021-00649-6.
Cardiovascular Cell Therapy Research NetworkLink provided by the sponsor.
National Heart, Lung, and Blood InstituteLink provided by the sponsor.
Information on stem cells from the National Institutes of HealthLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert Simari, MD study chair

CCTRN Steering Committee Chair

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Left Ventricular Ejection Fraction (LVEF) (time frame: Baseline to 6 months). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02501811, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.