Ischemic Cardiomyopathy
Conditions
Keywords
Heart Failure, Ischemia, Autologous Stem Cells, LV dysfunction, Mesenchymal Stem Cells, c-kit+ Cells, Combination Cell Therapy, LV function, Functional status
Brief 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, administered by transendocardial injection in subjects with ischemic cardiomyopathy.
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.
Interventions
BIOLOGICALMesenchymal Stem Cells (MSC)
15 transendocardial injections of 0.4ml MSCs administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
BIOLOGICALc-kit+ cells
15 transendocardial injections of 0.4ml c-kit+ cells administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
BIOLOGICALPlacebo (Plasmalyte A)
15 transendocardial injections of 0.4ml placebo administered to the left ventricle via NOGA Myostar injection catheter (single procedure)
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Be ≥ 21 and \<80 years of age 2. Have documented coronary artery disease (CAD) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF 3. Have a detectable area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by cMRI 4. Have an EF ≤ 40% by cMRI 5. 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. 6. Be a candidate for cardiac catheterization 7. Have NYHA class I, II, or III heart failure symptoms 8. 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
Exclusion criteria
1. 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 2. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe (any valve) insufficiency/regurgitation within 12 months of consent 3. Aortic stenosis with valve area ≤ 1.5 cm2 4. History of ischemic or hemorrhagic stroke within 90 days of consent 5. History of a left ventricular remodeling surgical procedure utilizing prosthetic material 6. Presence of a pacemaker and/or implantable cardioverter-defibrillator (ICD) generator with any of the following limitations/conditions: * 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 7. Pacemaker-dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded) 8. A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent 9. Other MRI contraindications (e.g. patient body habitus incompatible with MRI) 10. An appropriate ICD firing or anti-tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent 11. 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 12. Presence of LV thrombus 13. Evidence of active myocarditis 14. Baseline maximal oxygen consumption (VO2 max) greater than 75% of age and gender based predictive values 15. Baseline eGFR \<35 ml/min/1.73m2 16. Blood glucose levels (HbA1c) \>10% 17. Hematologic abnormality evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet count \< 100,000/ul 18. Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the upper limit of normal (ULN) 19. 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. 20. HIV and/or active hepatitis B virus (HBV) or hepatitis C virus (HCV) 21. Allergy to radiographic contrast material that cannot adequately be managed by premedication 22. Known history of anaphylactic reaction to penicillin or streptomycin 23. Received gene or cell-based therapy from any source within the previous 12 months 24. 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 25. Condition that limits lifespan to \< 1 year 26. 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 27. Participation in an investigational therapeutic or device trial within 30 days of consent 28. Cognitive or language barriers that prohibit obtaining informed consent or any study elements 29. Pregnancy or lactation or plans to become pregnant in the next 12 months 30. Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Days Alive and Out of Hospital for Heart Failure | 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. |
| Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory | 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 | 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 | 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 | 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 | 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) | 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 | 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 |
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | Baseline to 6 months | Change in left ventricular ejection fraction as assessed via cardiac MRI |
| Change From Baseline in Global Strain (HARP MRI) | Baseline to 6 months | Change in global circumferential strain as assessed via cardiac MRI |
| Change From Baseline in Regional Strain (HARP MRI) | 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) | 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) | 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 | 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) | Baseline to 6 months | Change in scar size percent as assessed via cardiac MRI |
| Change From Baseline in Scar Tissue Mass (DEMRI) | Baseline to 6 months | Change in scar tissue mass as assessed via cardiac MRI |
| Change From Baseline in Maximal Oxygen Consumption (Peak VO2) | 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) | 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subjects Who Have a Failed Bone Marrow Aspiration Procedure | During bone marrow aspiration procedure | Number and percent of subjects who do not successfully undergo bone marrow aspiration |
| Subjects Who Have a Failed Endomyocardial Biopsy Procedure | During endomyocardial biopsy procedure | Number and percent of subjects who do not successfully undergo endomyocardial biopsy procedure. Note only participants who were assigned to MSC+CPC or to CPC groups had endomyocardial biopsy procedures attempted. |
| Subject MSC Products Which Failed Release Criteria | Harvest to Study Product Injection Procedure | Number and percent of subjects who have MSC products which failed release criteria |
| Subject CPC Products Which Failed Release Criteria | Harvest to Study Project Injection procedure | Number and percent of subjects who have CPC products which failed release criteria |
| Subjects Who Receive Less Than 15 Injections During SPI | During SPI procedure | Number and percent of subjects who received less than 15 injections during SPI |
| Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | Baseline to 12 months | Number and percent of subjects who have at least one cardiac MRI endpoint measure that is uninterpretable due to issues related to the device, including, but not limited to, inability to undergo the procedure |
| Subjects With Events Between Randomization and Study Product Injection (SPI) That Preclude the Receipt of Product | Randomization to SPI, an average of 14 weeks | Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product. Reasons include those who did not undergo harvest (n=6; death, subject withdraw, subject changed mind) and those who did not undergo SPI (n=9; death, LVAD placement, episodes of ventricular tachycardia, and cancelled procedures) |
Countries
United States
Participant flow
Recruitment details
Enrollment took place at seven CCTRN centers between November 2016 and November 2018. The main centers are located in Texas, Florida (2 locations), Minnesota, Kentucky, Indiana, and California. Recruitment methods included www.clinicaltrials.gov, local heart failure clinics, and outreach to physician cardiologists. Original sample size of 144 was capped at 125 by NHLBI following review by DSMB of cell production, interim analysis, and power calculations. Power deemed adequate at 125 subjects.
Pre-assignment details
125 individuals consented, completed baseline testing, met eligibility criteria, and were randomized to study group. Reasons for failed eligibility (n=68) included investigator discretion, elevated LVEF, MRI contraindications, LV thrombus requiring anticoagulation therapy, elevated peak VO2, and other.
Participants by arm
| Arm | Count |
|---|---|
| MSCs + CPCs Target dose of 150 million MSCs and 5 million CPCs | 33 |
| MSCs Target dose of 150 million MSCs | 29 |
| CPCs Target dose of 5 million CPCs | 31 |
| Placebo Plasmalyte A | 32 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 3 | 2 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 2 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | CPCs | MSCs | MSCs + CPCs |
|---|---|---|---|---|---|
| ACE Inhibitors | 52 Participants | 8 Participants | 18 Participants | 10 Participants | 16 Participants |
| Age, Continuous | 62.5 years STANDARD_DEVIATION 8.9 | 63.1 years STANDARD_DEVIATION 8 | 64.2 years STANDARD_DEVIATION 8.1 | 61.7 years STANDARD_DEVIATION 6.7 | 61.0 years STANDARD_DEVIATION 11.1 |
| Aldosterone Antagonists | 80 Participants | 22 Participants | 20 Participants | 20 Participants | 18 Participants |
| Angiotensin II Blockers | 28 Participants | 9 Participants | 6 Participants | 5 Participants | 8 Participants |
| Atrial Fibrillation | 40 Participants | 10 Participants | 11 Participants | 8 Participants | 11 Participants |
| Beta Blockers | 118 Participants | 31 Participants | 29 Participants | 26 Participants | 32 Participants |
| Body Mass Index | 30.3 kg/m^2 STANDARD_DEVIATION 4.6 | 30.0 kg/m^2 STANDARD_DEVIATION 4.4 | 29.4 kg/m^2 STANDARD_DEVIATION 5 | 30.4 kg/m^2 STANDARD_DEVIATION 5.4 | 31.2 kg/m^2 STANDARD_DEVIATION 3.5 |
| Coronary Artery Bypass Grafting (CABG) | 62 Participants | 15 Participants | 16 Participants | 14 Participants | 17 Participants |
| Diabetes | 39 Participants | 12 Participants | 10 Participants | 10 Participants | 7 Participants |
| Diastolic Blood Pressure | 69.0 mmHg STANDARD_DEVIATION 10.1 | 67.7 mmHg STANDARD_DEVIATION 11.2 | 68.3 mmHg STANDARD_DEVIATION 10.8 | 70.1 mmHg STANDARD_DEVIATION 9 | 70.2 mmHg STANDARD_DEVIATION 9.3 |
| Entresto | 39 Participants | 13 Participants | 7 Participants | 11 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 4 Participants | 6 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 28 Participants | 25 Participants | 22 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Hypertension | 105 Participants | 27 Participants | 26 Participants | 23 Participants | 29 Participants |
| Multi-Vessel Disease | 105 Participants | 30 Participants | 28 Participants | 22 Participants | 25 Participants |
| New York Heart Association Class 1 | 6 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| New York Heart Association Class 2 | 100 Participants | 28 Participants | 26 Participants | 22 Participants | 24 Participants |
| New York Heart Association Class 3 | 19 Participants | 3 Participants | 2 Participants | 6 Participants | 8 Participants |
| Number of Myocardial Infarctions | 1.8 events STANDARD_DEVIATION 1.3 | 1.7 events STANDARD_DEVIATION 1 | 1.9 events STANDARD_DEVIATION 1.2 | 1.9 events STANDARD_DEVIATION 1.7 | 1.6 events STANDARD_DEVIATION 1 |
| Ongoing Ischemia | 25 Participants | 7 Participants | 4 Participants | 5 Participants | 9 Participants |
| Percutaneous Coronary Intervention (PCI) | 106 Participants | 28 Participants | 27 Participants | 24 Participants | 27 Participants |
| Presence of a Cardiac Device | 101 Participants | 21 Participants | 28 Participants | 24 Participants | 28 Participants |
| Previous Emergency Department Visit for Heart Failure | 27 Participants | 9 Participants | 8 Participants | 4 Participants | 6 Participants |
| Previous Hospitalization for Heart Failure | 41 Participants | 13 Participants | 9 Participants | 8 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 113 Participants | 28 Participants | 28 Participants | 27 Participants | 30 Participants |
| Region of Enrollment United States | 125 participants | 32 participants | 31 participants | 29 participants | 33 participants |
| Sex: Female, Male Female | 9 Participants | 1 Participants | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 116 Participants | 31 Participants | 27 Participants | 27 Participants | 31 Participants |
| Smoking (Lifetime) | 83 Participants | 22 Participants | 24 Participants | 18 Participants | 19 Participants |
| Sustained Ventricular Arrhythmia | 28 Participants | 7 Participants | 4 Participants | 5 Participants | 12 Participants |
| Systolic Blood Pressure | 116.8 mmHg STANDARD_DEVIATION 16.5 | 117.2 mmHg STANDARD_DEVIATION 17.6 | 117.3 mmHg STANDARD_DEVIATION 17.9 | 114.0 mmHg STANDARD_DEVIATION 11.3 | 118.4 mmHg STANDARD_DEVIATION 18.2 |
| Valvular Heart Disease | 89 Participants | 24 Participants | 26 Participants | 17 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 33 | 3 / 29 | 2 / 31 | 4 / 32 |
| other Total, other adverse events | 10 / 33 | 6 / 29 | 14 / 31 | 15 / 32 |
| serious Total, serious adverse events | 14 / 33 | 14 / 29 | 13 / 31 | 18 / 32 |
Outcome results
Primary
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.
Time frame: Baseline to 6 months
Population: Participants with available analyzable exercise tolerance data at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Exercise Tolerance (Six Minute Walk Test) | 19.24 meters | Standard Deviation 71.65 |
| MSCs | Change From Baseline in Exercise Tolerance (Six Minute Walk Test) | 23.85 meters | Standard Deviation 57.03 |
| CPCs | Change From Baseline in Exercise Tolerance (Six Minute Walk Test) | 2.36 meters | Standard Deviation 44.3 |
| Placebo | Change From Baseline in Exercise Tolerance (Six Minute Walk Test) | 0.67 meters | Standard Deviation 70.54 |
p-value: 0.34895% CI: [-19.537, 56.687]ANCOVA
p-value: 0.2395% CI: [-12.759, 59.134]ANCOVA
p-value: 0.90595% CI: [-30.974, 34.361]ANCOVA
p-value: 0.33595% CI: [-15.267, 49.03]ANCOVA
p-value: 0.82795% CI: [-40.106, 30.88]ANCOVA
p-value: 0.16395% CI: [-50.989, 8.001]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable six minute walk tests at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory | 9.996 meters | Standard Error 5.558 |
| MSCs | Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory | 11.434 meters | Standard Error 5.531 |
| CPCs | Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory | 6.776 meters | Standard Error 6.192 |
| Placebo | Change From Baseline in Exercise Tolerance (Six Minute Walk Test)-Trajectory | -4.248 meters | Standard Error 5.215 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.025Repeated Measures Linear Regression
Primary
Change From Baseline in Global Strain (HARP MRI)
Change in global circumferential strain as assessed via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available analyzable global circumferential strain at baseline and 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Global Strain (HARP MRI) | -0.36 percent | Standard Deviation 3.2 |
| MSCs | Change From Baseline in Global Strain (HARP MRI) | 0.48 percent | Standard Deviation 3.36 |
| CPCs | Change From Baseline in Global Strain (HARP MRI) | 0.56 percent | Standard Deviation 2.08 |
| Placebo | Change From Baseline in Global Strain (HARP MRI) | -0.10 percent | Standard Deviation 3.38 |
p-value: 0.94295% CI: [-2.406, 1.887]ANCOVA
p-value: 0.28295% CI: [-1.815, 2.975]ANCOVA
p-value: 0.16395% CI: [-1.31, 2.635]ANCOVA
p-value: 0.17595% CI: [-2.471, 0.628]ANCOVA
p-value: 0.32995% CI: [-2.932, 1.254]ANCOVA
p-value: 0.75295% CI: [-1.829, 1.994]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had available analyzable global circumferential strain at baseline, 6 month, and 12 month.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Global Strain (HARP MRI)-Trajectory | 0.126 percent | Standard Error 0.239 |
| MSCs | Change From Baseline in Global Strain (HARP MRI)-Trajectory | -0.324 percent | Standard Error 0.283 |
| CPCs | Change From Baseline in Global Strain (HARP MRI)-Trajectory | 0.276 percent | Standard Error 0.3 |
| Placebo | Change From Baseline in Global Strain (HARP MRI)-Trajectory | 0.576 percent | Standard Error 0.417 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.361Repeated Measures Linear Regression
Primary
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Change in left ventricular ejection fraction as assessed via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available analyzable LVEF at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | -0.42 percentage of end diastolic volume | Standard Deviation 3.9 |
| MSCs | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | 0.37 percentage of end diastolic volume | Standard Deviation 2.95 |
| CPCs | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | 1.05 percentage of end diastolic volume | Standard Deviation 3.68 |
| Placebo | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) | -0.33 percentage of end diastolic volume | Standard Deviation 3.73 |
p-value: 0.99395% CI: [-2.19, 2.023]ANCOVA
p-value: 0.49995% CI: [-1.229, 2.635]ANCOVA
p-value: 0.57895% CI: [-0.729, 3.485]ANCOVA
p-value: 0.52395% CI: [-3.552, 0.629]ANCOVA
p-value: 0.47195% CI: [-2.7, 1.127]ANCOVA
p-value: 0.48595% CI: [-1.24, 2.59]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable LVEF at baseline, 6 months, and 12 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory | 0.167 percentage of end diastolic volume | Standard Error 0.551 |
| MSCs | Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory | 0.422 percentage of end diastolic volume | Standard Error 0.48 |
| CPCs | Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory | 0.633 percentage of end diastolic volume | Standard Error 0.411 |
| Placebo | Change From Baseline in Left Ventricular Ejection Fraction (LVEF)-Trajectory | -0.175 percentage of end diastolic volume | Standard Error 0.332 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reportedp-value: 0.269Repeated Measures Linear Regression
Primary
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)
Change in left ventricular end diastolic volume index as measured via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available analyzable LVEDVI at baseline and six months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) | 0.97 mL/m^2 | Standard Deviation 16.06 |
| MSCs | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) | 0.21 mL/m^2 | Standard Deviation 11.91 |
| CPCs | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) | -1.13 mL/m^2 | Standard Deviation 12.37 |
| Placebo | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) | 2.99 mL/m^2 | Standard Deviation 11.84 |
p-value: 0.60295% CI: [-9.754, 5.711]ANCOVA
p-value: 0.44395% CI: [-9.609, 4.044]ANCOVA
p-value: 0.34895% CI: [-11.011, 2.76]ANCOVA
p-value: 0.81295% CI: [-5.76, 9.968]ANCOVA
p-value: 0.995% CI: [-7.052, 8.574]ANCOVA
p-value: 0.84895% CI: [-8.321, 5.635]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable LVEDVI at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory | 1.538 mL/m^2 | Standard Error 1.585 |
| MSCs | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory | 0.320 mL/m^2 | Standard Error 1.303 |
| CPCs | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory | 1.796 mL/m^2 | Standard Error 1.393 |
| Placebo | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI)-Trajectory | 1.862 mL/m^2 | Standard Error 1.98 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.095Repeated Measures Linear Regression
Primary
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)
Change in left ventricular end systolic volume index as assessed via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available analyzable LVESVI at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) | 0.98 mL/m^2 | Standard Deviation 11.17 |
| MSCs | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) | -0.22 mL/m^2 | Standard Deviation 10.75 |
| CPCs | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) | -2.37 mL/m^2 | Standard Deviation 11.09 |
| Placebo | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI) | 2.23 mL/m^2 | Standard Deviation 10.69 |
p-value: 0.65995% CI: [-7.281, 4.789]ANCOVA
p-value: 0.46695% CI: [-8.621, 3.71]ANCOVA
p-value: 0.29395% CI: [-10.799, 1.594]ANCOVA
p-value: 0.5395% CI: [-2.795, 9.508]ANCOVA
p-value: 0.76195% CI: [-4.91, 7.33]ANCOVA
p-value: 0.66995% CI: [-8.426, 4.132]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, 12 months)
Population: Participants who had analyzable LVESVI at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory | 0.826 mL/m^2 | Standard Error 1.158 |
| MSCs | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory | -0.394 mL/m^2 | Standard Error 1.117 |
| CPCs | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory | 0.626 mL/m^2 | Standard Error 1.288 |
| Placebo | Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVI)-Trajectory | 1.077 mL/m^2 | Standard Error 1.709 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.379Repeated Measures Linear Regression
Primary
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.
Time frame: Baseline to 6 months
Population: Participants with available analyzable LV sphericity index at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular Sphericity Index | 0.00 ratio-unitless | Standard Deviation 0.07 |
| MSCs | Change From Baseline in Left Ventricular Sphericity Index | -0.00 ratio-unitless | Standard Deviation 0.07 |
| CPCs | Change From Baseline in Left Ventricular Sphericity Index | 0.00 ratio-unitless | Standard Deviation 0.08 |
| Placebo | Change From Baseline in Left Ventricular Sphericity Index | 0.01 ratio-unitless | Standard Deviation 0.08 |
p-value: 0.90495% CI: [-0.041, 0.047]ANCOVA
p-value: 0.98995% CI: [-0.048, 0.04]ANCOVA
p-value: 0.49395% CI: [-0.056, 0.033]ANCOVA
p-value: 0.92695% CI: [-0.053, 0.039]ANCOVA
p-value: 0.47695% CI: [-0.035, 0.049]ANCOVA
p-value: 0.51595% CI: [-0.04, 0.048]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable LV Sphericity Index at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Left Ventricular Sphericity Index-Trajectory | 0.004 ratio-unitless | Standard Error 0.007 |
| MSCs | Change From Baseline in Left Ventricular Sphericity Index-Trajectory | -0.004 ratio-unitless | Standard Error 0.008 |
| CPCs | Change From Baseline in Left Ventricular Sphericity Index-Trajectory | 0.008 ratio-unitless | Standard Error 0.007 |
| Placebo | Change From Baseline in Left Ventricular Sphericity Index-Trajectory | 0.002 ratio-unitless | Standard Error 0.012 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.401Repeated Measures Linear Regression
Primary
Change From Baseline in Maximal Oxygen Consumption (Peak VO2)
Change in maximal oxygen consumption (peak V02) as assessed via treadmill
Time frame: Baseline to 6 months
Population: Participants with available analyzable peak VO2 data from baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Maximal Oxygen Consumption (Peak VO2) | -0.89 ml/kg/min | Standard Deviation 2.94 |
| MSCs | Change From Baseline in Maximal Oxygen Consumption (Peak VO2) | -0.83 ml/kg/min | Standard Deviation 3.75 |
| CPCs | Change From Baseline in Maximal Oxygen Consumption (Peak VO2) | 0.77 ml/kg/min | Standard Deviation 2.86 |
| Placebo | Change From Baseline in Maximal Oxygen Consumption (Peak VO2) | 0.13 ml/kg/min | Standard Deviation 2.28 |
p-value: 0.15795% CI: [-2.456, 0.411]ANCOVA
p-value: 0.42895% CI: [-2.798, 0.859]ANCOVA
p-value: 0.38295% CI: [-0.83, 2.093]ANCOVA
p-value: 0.05695% CI: [-3.255, -0.052]ANCOVA
p-value: 0.6195% CI: [-1.991, 1.885]ANCOVA
p-value: 0.19595% CI: [-0.356, 3.557]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable peak VO2 at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Maximal Oxygen Consumption (Peak VO2)-Trajectory | -0.711 ml/kg/min | Standard Error 0.352 |
| MSCs | Change From Baseline in Maximal Oxygen Consumption (Peak VO2)-Trajectory | 0.632 ml/kg/min | Standard Error 0.275 |
| CPCs | Change From Baseline in Maximal Oxygen Consumption (Peak VO2)-Trajectory | -0.165 ml/kg/min | Standard Error 0.325 |
| Placebo | Change From Baseline in Maximal Oxygen Consumption (Peak VO2)-Trajectory | -0.093 ml/kg/min | Standard Error 0.369 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.472Repeated Measures Linear Regression
Primary
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.
Time frame: Baseline to 6 months
Population: Participants with available analyzable MLHFQ summary score at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score | -15.32 score on a scale | Standard Deviation 16.94 |
| MSCs | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score | -20.78 score on a scale | Standard Deviation 23.11 |
| CPCs | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score | -8.65 score on a scale | Standard Deviation 23.72 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score | -5.68 score on a scale | Standard Deviation 18.23 |
p-value: 0.02395% CI: [-18.915, -0.357]ANCOVA
p-value: 0.0595% CI: [-26.871, -3.319]ANCOVA
p-value: 0.11995% CI: [-14.784, 8.836]ANCOVA
p-value: 0.84595% CI: [-18.087, 4.762]ANCOVA
p-value: 0.97695% CI: [-5.931, 16.848]ANCOVA
p-value: 0.71795% CI: [-1.337, 25.578]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable MLHFQ scores at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score-Trajectory | -9.258 score on a scale | Standard Error 2.079 |
| MSCs | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score-Trajectory | -7.295 score on a scale | Standard Error 2.746 |
| CPCs | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score-Trajectory | 0.776 score on a scale | Standard Error 1.731 |
| Placebo | Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Score-Trajectory | -2.378 score on a scale | Standard Error 2.357 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. A time by treatment interaction was assessed.p-value: 0.037Regression, Linear
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. A time by treatment interaction was assessed.p-value: 0.035Regression, Linear
Primary
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
Time frame: Baseline to 6 months
Population: Participants with available analyzable NT-proBNP values at baseline and 6 months. Log transformation used. P-values obtained from transformed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | -724.46 pg/ml | Standard Deviation 4020.53 |
| MSCs | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | 52.6 pg/ml | Standard Deviation 586.16 |
| CPCs | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | 204.09 pg/ml | Standard Deviation 533.51 |
| Placebo | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | 687.25 pg/ml | Standard Deviation 2006.72 |
p-value: 0.1195% CI: [-3108.3, 284.9]ANCOVA
p-value: 0.11295% CI: [-1460.7, 191.4]ANCOVA
p-value: 0.89195% CI: [-1301.5, 335.2]ANCOVA
p-value: 0.00995% CI: [-2470.7, 613.6]ANCOVA
p-value: 0.66195% CI: [-2323.2, 769.1]ANCOVA
p-value: 0.01595% CI: [-175.4, 478.4]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable NT-proBNP values at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory | 74.650 pg/ml | Standard Error 72.303 |
| MSCs | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory | 102.250 pg/ml | Standard Error 46.194 |
| CPCs | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory | 61.680 pg/ml | Standard Error 57.365 |
| Placebo | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)-Trajectory | 185.210 pg/ml | Standard Error 99.19 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.092Repeated Measures Linear Regression
Primary
Change From Baseline in Regional Strain (HARP MRI)
Change in regional longitudinal strain as assessed via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available analyzable regional longitudinal strain at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Regional Strain (HARP MRI) | -0.50 percent | Standard Deviation 2.33 |
| MSCs | Change From Baseline in Regional Strain (HARP MRI) | -0.51 percent | Standard Deviation 2.33 |
| CPCs | Change From Baseline in Regional Strain (HARP MRI) | -0.76 percent | Standard Deviation 2.49 |
| Placebo | Change From Baseline in Regional Strain (HARP MRI) | -0.91 percent | Standard Deviation 2.44 |
p-value: 0.73395% CI: [-1.118, 1.927]ANCOVA
p-value: 0.73595% CI: [-1.248, 2.041]ANCOVA
p-value: 0.79495% CI: [-1.464, 1.767]ANCOVA
p-value: 0.95195% CI: [-1.161, 1.666]ANCOVA
p-value: 0.96295% CI: [-1.441, 1.457]ANCOVA
p-value: 0.94595% CI: [-1.793, 1.303]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable regional strain at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Regional Strain (HARP MRI)-Trajectory | -0.084 percent | Standard Error 0.287 |
| MSCs | Change From Baseline in Regional Strain (HARP MRI)-Trajectory | -0.385 percent | Standard Error 0.35 |
| CPCs | Change From Baseline in Regional Strain (HARP MRI)-Trajectory | -0.325 percent | Standard Error 0.323 |
| Placebo | Change From Baseline in Regional Strain (HARP MRI)-Trajectory | -0.288 percent | Standard Error 0.36 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.107Repeated Measures Linear Regression
Primary
Change From Baseline in Scar Size Percent (DEMRI)
Change in scar size percent as assessed via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available and analyzable scar size data at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Scar Size Percent (DEMRI) | -0.57 percentage of mass | Standard Deviation 3.25 |
| MSCs | Change From Baseline in Scar Size Percent (DEMRI) | -0.70 percentage of mass | Standard Deviation 2.8 |
| CPCs | Change From Baseline in Scar Size Percent (DEMRI) | -1.06 percentage of mass | Standard Deviation 2.4 |
| Placebo | Change From Baseline in Scar Size Percent (DEMRI) | -0.53 percentage of mass | Standard Deviation 2.29 |
p-value: 0.56995% CI: [-1.77, 1.687]ANCOVA
p-value: 0.76795% CI: [-1.792, 1.457]ANCOVA
p-value: 0.26195% CI: [-1.965, 0.921]ANCOVA
p-value: 0.58795% CI: [-1.261, 2.222]ANCOVA
p-value: 0.99495% CI: [-1.763, 2.014]ANCOVA
p-value: 0.63995% CI: [-1.993, 1.283]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable scar size percent at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Scar Size Percent (DEMRI)-Trajectory | -0.341 percentage of mass | Standard Error 0.314 |
| MSCs | Change From Baseline in Scar Size Percent (DEMRI)-Trajectory | -0.290 percentage of mass | Standard Error 0.231 |
| CPCs | Change From Baseline in Scar Size Percent (DEMRI)-Trajectory | -0.427 percentage of mass | Standard Error 0.306 |
| Placebo | Change From Baseline in Scar Size Percent (DEMRI)-Trajectory | -0.013 percentage of mass | Standard Error 0.34 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.126Repeated Measures Linear Regression
Primary
Change From Baseline in Scar Tissue Mass (DEMRI)
Change in scar tissue mass as assessed via cardiac MRI
Time frame: Baseline to 6 months
Population: Participants with available and analyzable scar size data at baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Scar Tissue Mass (DEMRI) | -0.87 grams | Standard Deviation 5.21 |
| MSCs | Change From Baseline in Scar Tissue Mass (DEMRI) | -1.13 grams | Standard Deviation 3.71 |
| CPCs | Change From Baseline in Scar Tissue Mass (DEMRI) | -2.51 grams | Standard Deviation 4.51 |
| Placebo | Change From Baseline in Scar Tissue Mass (DEMRI) | -1.31 grams | Standard Deviation 4.07 |
p-value: 0.99295% CI: [-2.437, 3.319]ANCOVA
p-value: 0.86295% CI: [-2.278, 2.643]ANCOVA
p-value: 0.21795% CI: [-3.846, 1.443]ANCOVA
p-value: 0.32795% CI: [-1.325, 4.611]ANCOVA
p-value: 0.85995% CI: [-2.551, 3.068]ANCOVA
p-value: 0.33895% CI: [-3.952, 1.184]ANCOVA
Primary
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.
Time frame: Assessed as a trajectory (baseline, 6 months, and 12 months)
Population: Participants who had analyzable scar size data at baseline, 6 months, and 12 months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory | -0.309 grams | Standard Error 0.539 |
| MSCs | Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory | -0.266 grams | Standard Error 0.367 |
| CPCs | Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory | -0.958 grams | Standard Error 0.615 |
| Placebo | Change From Baseline in Scar Tissue Mass (DEMRI)-Trajectory | -0.390 grams | Standard Error 0.549 |
Comparison: Repeated-measures linear regression models were used to address trajectories (upward or downward trends) over time within each of the 4 treatment groups. Results of the overall model are reported.p-value: 0.139Repeated Measures Linear Regression
Primary
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.
Time frame: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Population: Comparison of the 4 treatment groups on days alive and out of the hospital for heart failure during the 12 month study evaluation period; adjusted for time in followup. Analysis includes all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MSCs + CPCs | Cumulative Days Alive and Out of Hospital for Heart Failure | 472 days | Standard Deviation 121 |
| MSCs | Cumulative Days Alive and Out of Hospital for Heart Failure | 448 days | Standard Deviation 120 |
| CPCs | Cumulative Days Alive and Out of Hospital for Heart Failure | 438 days | Standard Deviation 163 |
| Placebo | Cumulative Days Alive and Out of Hospital for Heart Failure | 427 days | Standard Deviation 158 |
Primary
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
Time frame: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Population: Population includes all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Participants Experiencing Other Significant Clinical Events | 8 Participants |
| MSCs | Participants Experiencing Other Significant Clinical Events | 3 Participants |
| CPCs | Participants Experiencing Other Significant Clinical Events | 11 Participants |
| Placebo | Participants Experiencing Other Significant Clinical Events | 7 Participants |
Primary
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).
Time frame: Baseline to End of 12 Month Visit Window, an average of 395 days following study product injection
Population: Population includes all randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Participants With Major Adverse Cardiac Events (MACE) | 3 Participants |
| MSCs | Participants With Major Adverse Cardiac Events (MACE) | 7 Participants |
| CPCs | Participants With Major Adverse Cardiac Events (MACE) | 2 Participants |
| Placebo | Participants With Major Adverse Cardiac Events (MACE) | 9 Participants |
Other Pre-specified
Subject CPC Products Which Failed Release Criteria
Number and percent of subjects who have CPC products which failed release criteria
Time frame: Harvest to Study Project Injection procedure
Population: Population includes only those participant products assigned to treatment groups including CPCs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subject CPC Products Which Failed Release Criteria | 5 Participants |
| CPCs | Subject CPC Products Which Failed Release Criteria | 4 Participants |
Other Pre-specified
Subject MSC Products Which Failed Release Criteria
Number and percent of subjects who have MSC products which failed release criteria
Time frame: Harvest to Study Product Injection Procedure
Population: Population includes only those participant products assigned to treatment groups including MSCs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subject MSC Products Which Failed Release Criteria | 8 Participants |
| MSCs | Subject MSC Products Which Failed Release Criteria | 6 Participants |
Other Pre-specified
Subjects Who Have a Failed Bone Marrow Aspiration Procedure
Number and percent of subjects who do not successfully undergo bone marrow aspiration
Time frame: During bone marrow aspiration procedure
Population: Participants who attended their harvest visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subjects Who Have a Failed Bone Marrow Aspiration Procedure | 0 Participants |
| MSCs | Subjects Who Have a Failed Bone Marrow Aspiration Procedure | 0 Participants |
| CPCs | Subjects Who Have a Failed Bone Marrow Aspiration Procedure | 0 Participants |
| Placebo | Subjects Who Have a Failed Bone Marrow Aspiration Procedure | 0 Participants |
Other Pre-specified
Subjects Who Have a Failed Endomyocardial Biopsy Procedure
Number and percent of subjects who do not successfully undergo endomyocardial biopsy procedure. Note only participants who were assigned to MSC+CPC or to CPC groups had endomyocardial biopsy procedures attempted.
Time frame: During endomyocardial biopsy procedure
Population: Participants who attended the harvest visit and were assigned to either MSCs+CPCs or CPCs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subjects Who Have a Failed Endomyocardial Biopsy Procedure | 0 Participants |
| MSCs | Subjects Who Have a Failed Endomyocardial Biopsy Procedure | 0 Participants |
| CPCs | Subjects Who Have a Failed Endomyocardial Biopsy Procedure | 1 Participants |
| Placebo | Subjects Who Have a Failed Endomyocardial Biopsy Procedure | 0 Participants |
Other Pre-specified
Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable
Number and percent of subjects who have at least one cardiac MRI endpoint measure that is uninterpretable due to issues related to the device, including, but not limited to, inability to undergo the procedure
Time frame: Baseline to 12 months
Population: Participants completing an MRI scan at both baseline and 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | 5 Participants |
| MSCs | Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | 1 Participants |
| CPCs | Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | 1 Participants |
| Placebo | Subjects Who Have at Least One Cardiac MRI Endpoint Measure That is Uninterpretable | 3 Participants |
Other Pre-specified
Subjects Who Receive Less Than 15 Injections During SPI
Number and percent of subjects who received less than 15 injections during SPI
Time frame: During SPI procedure
Population: Participants who received study product administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subjects Who Receive Less Than 15 Injections During SPI | 2 Participants |
| MSCs | Subjects Who Receive Less Than 15 Injections During SPI | 0 Participants |
| CPCs | Subjects Who Receive Less Than 15 Injections During SPI | 1 Participants |
| Placebo | Subjects Who Receive Less Than 15 Injections During SPI | 1 Participants |
Other Pre-specified
Subjects With Events Between Randomization and Study Product Injection (SPI) That Preclude the Receipt of Product
Number and percent of subjects with events between randomization and study product injection (SPI) that preclude the subject from receiving product. Reasons include those who did not undergo harvest (n=6; death, subject withdraw, subject changed mind) and those who did not undergo SPI (n=9; death, LVAD placement, episodes of ventricular tachycardia, and cancelled procedures)
Time frame: Randomization to SPI, an average of 14 weeks
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MSCs + CPCs | Subjects With Events Between Randomization and Study Product Injection (SPI) That Preclude the Receipt of Product | 3 Participants |
| MSCs | Subjects With Events Between Randomization and Study Product Injection (SPI) That Preclude the Receipt of Product | 4 Participants |
| CPCs | Subjects With Events Between Randomization and Study Product Injection (SPI) That Preclude the Receipt of Product | 4 Participants |
| Placebo | Subjects With Events Between Randomization and Study Product Injection (SPI) That Preclude the Receipt of Product | 4 Participants |