Chronic Ischemic Left Ventricular Dysfunction, Myocardial Infarction
Conditions
Keywords
Cardiovascular, Chronic Ischemic Left Ventricular Dysfunction
Brief summary
Thirty (30) patients with chronic ischemic left ventricular dysfunction secondary to MI scheduled to undergo cardiac catheterization will be enrolled in the study. This is a phase II study intended to gain additional safety and efficacy assessments among two dose levels previously studied in a phase I setting.
Detailed description
Thirty (30) patients with chronic ischemic left ventricular dysfunction secondary to MI scheduled to undergo cardiac catheterization will be enrolled in the study.This is a phase II study intended to gain additional safety and efficacy assessments among two dose levels previously studied in a phase I setting. In this study, a 20 million total hMSC dose and a 100 million total hMSC dose will be randomly allocated administered via the Biocardia Helical infusion system in a blinded manner. The technique of transplanting progenitor cells into a region of damaged myocardium, termed cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be readily available, easy to culture to ensure adequate quantities for transplantation, and able to survive in host myocardium, which is often a hostile environment of limited blood supply and immunorejection. Whether effective cellular regenerative strategies require that administered cells differentiate into adult cardiomyocytes and couple electromechanically with the surrounding myocardium is increasingly controversial and recent evidence suggests that this may not be required for effective cardiac repair. Most importantly, transplantation of graft cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a number of candidate cells have been transplanted in experimental models, including fetal and neonatal cardiomyocytes, embryonic stem cell-derived myocytes, tissue engineered contractile grafts9, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac precursors residing within the heart itself. There has been substantial clinical development in the use of whole bone marrow and skeletal myoblast preparations in studies enrolling both post-infarction patients and patients with chronic ischemic left ventricular dysfunction and heart failure. The effects of bone marrow-derived mesenchymal stem cells (MSCs) have also been studied clinically. Currently, bone marrow or bone marrow-derived cells represent a highly promising modality for cardiac repair. The totality of evidence from trials investigating autologous whole bone marrow infusions into patients following myocardial infarction supports the safety of this approach. In terms of efficacy, increases in ejection fraction are reported in the majority of the trials. Chronic ischemic left ventricular dysfunction is a common and problematic condition; definitive therapy in the form of heart transplantation is available to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for acute MI, but represents a potentially important alternative for this disease.
Interventions
BIOLOGICALAllogeneic hMSCs
Allogeneic Adult Human Mesenchymal Stem Cells (MSCs) delivered via injection
Sponsors
The Emmes Company, LLC
Joshua M Hare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* In order to participate in this study, a patient MUST: 1. Be ≥ 21 and \< 90 years of age. 2. Provide written informed consent. 3. Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by previous myocardial infarction documented by an imaging study demonstrating coronary artery disease with corresponding areas of akinesis, dyskinesis, or severe hypokinesis. 4. Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 month. 5. Be a candidate for cardiac catheterization within 5 to 10 weeks of screening as determined by doctors. 6. Have an ejection fraction of less than or equal to 50% by gated blood pool scan, two-dimensional echocardiogram, CT, or left ventriculogram within the prior six months and not in the setting of a recent ischemic event.
Exclusion criteria
* In order to participate in this study, a patient MUST NOT: 1. Have a baseline glomerular filtration rate ≤ 35 ml/min/1.73m2. 2. Have a known, serious radiographic contrast allergy. 3. Have a Mechanical aortic valve or heart constrictive device. 4. Have a documented presence of aortic stenosis (aortic stenosis graded as 1.5cm2 or less). 5. Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2). 6. Require coronary artery revascularization. Patients who require or undergo revascularization procedures should undergo these procedures a minimum of 3 months in advance of treatment in this study. In addition, patients who develop a need for revascularization following enrollment will be submitted for this therapy without delay. 7. Have evidence of a life-threatening arrhythmia in the absence of a defibrillator (non-sustained ventricular tachycardia ≥ 20 consecutive beats or complete second or third degree heart block in the absence of a functioning pacemaker) or Corrected for heart rate (QTc) interval \> 550 ms on screening ECG 8. Automatic Implantable Cardioverter Defibrillator (AICD) firing in the past 60 days prior to enrollment. 9. Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cell \< 2,500/µl or platelet values \< 100,000/µl without another explanation. 10. Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the upper limit of normal (ULN). 11. Have a coagulopathy = (INR \> 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR \< 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment 12. Have known allergies to penicillin or streptomycin. 13. Hypersensitivity to Dimethyl Sulfoxide (DMSO). 14. Be an organ transplant recipient. 15. Have a history of organ or cell transplant rejection 16. Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma. 17. Have a non-cardiac condition that limits lifespan to \< 1 year. 18. Have a history of drug or alcohol abuse within the past 24 months. 19. Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists. 20. Be serum positive for HIV, hepatitis BsAg or viremic hepatitis C. 21. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial. 22. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Serious Adverse Events (SAE). | One month post-catheterization | Incidence (at one month post-catheterization) of any treatment-emergent serious adverse events, defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant With Reported Tissue Perfusion | 6 months, 12 months | Tissue perfusion measured by CT. |
| Peak Oxygen Consumption (VO2) | Baseline, 6 months, 12 months | Peak VO2 assessed via treadmill determination. |
| Six-minute Walk Test. | Baseline, 3 months, 6 months, 12 months | A test that measures how far a patient can walk in 6 minutes. |
| Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Baseline to 6 months, Baseline to 12 months | Changed in NYHA Functional Classification will be evaluated. Worsened: Documented increase in limitation in physical activity. Improved: Documented decrease in limitation in physical activity. Unchanged: No documented change in limitation in physical activity. |
| Number of Incidents of Major Adverse Cardiac Events (MACE). | 1 month, 6 months, 12 months post injection. | Incidence of the Major Adverse Cardiac Events (MACE) endpoint, defined as the composite incidence of (1) death, (2) hospitalization for worsening heart failure, or (3) non-fatal recurrent MI. |
| Number of Participants With Treatment Emergent Adverse Event (AE) | 6 months, 12 months | Incidence of Treatment Emergent Adverse Event defined as any untoward medical occurrence in a patient or clinical investigation subject temporally associated with the use of the study product. |
| Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | Baseline, 3 months, 6 months, 12 months | Minnesota Living with Heart Failure (MLHF) Questionnaire has a total score from 0 to 105. A higher score indicates that participant's heart failure is preventing them from living their life. |
| Echocardiographic-derived Measures of Left Ventricular Function | 6 months, 12 months | Left ventricular end diastolic wall thickness as determined by echocardiogram. |
| Difference Between Regional Left Ventricular Function (at the Site of Allogeneic Cell Injections) | Baseline, 12 Months | As determined by Computed Tomography Scan |
| Difference Between the Regional Left Ventricular Wall Thickening | Baseline, Month 12 | As determined by Computed Tomography Scan |
| Infarct Scar Size (ISS) | Baseline, 12 months | Determined by delayed contrast enhanced Computed Tomography (CT) Scan |
| Difference Between the Left Ventricular Ejection Fraction (LVEF) | Baseline, 12 months | Change in 1-year LVEF by CT as compared to baseline. |
| Difference in LVEF | Baseline, 6 months, 12 months | As assessed via ECHO |
| Difference in Left Ventricular Volume | Baseline, 6 months, 12 months | Difference in left ventricular end diastolic and end systolic volume will be assessed via ECHO |
| Difference in Left Ventricular Regional Myocardial Perfusion | Baseline, 12 months | As measured via myocardial mass by CT |
| Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months | The number of participants with abnormal ECG readings via 24 hour ambulatory ECG recordings as assessed per treating physician discretion. |
| Number of Clinically Significant of Abnormal Lab Values. | 12 months | Clinical significance of abnormal lab values will be assessed by treating physician |
| Serial Troponin I | 12 hours, 24 hours post cardiac catheterization | Serial Troponin I values in ng/mL over time. |
| Number of Participants With Abnormal ECHO Reading | 6 hours post cardiac catheterization | The number of participants with abnormal reading post-cardiac catheterization. As assessed per treating physician discretion. |
| Creatinine Kinase Muscle/Brain (CK-MB) | 12 hours, 24 hours post cardiac catheterization | CK-MB values in ng/mL over time. |
| Difference Between Left Ventricular End Diastolic Wall Thickness | Baseline, 12 Months | As determined by Computed Tomography Scan |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: 20 Million Allogeneic hMSCs Fifteen (15) patients to be treated with Allo-hMSCs: 4 million cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 0.2x 10\^8 (20 million) Allo-hMSCs.
Allogeneic hMSCs: Allogeneic Adult Human Mesenchymal Stem Cells (MSCs) delivered via injection | 15 |
| Group 2: 100 Million Allogeneic hMSCs Fifteen (15) patients to be treated with Allo-hMSCs: 20 million cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1x 10\^8 (100 million) Allo-hMSCs.
Allogeneic hMSCs: Allogeneic Adult Human Mesenchymal Stem Cells (MSCs) delivered via injection | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Group 2: 100 Million Allogeneic hMSCs | Group 1: 20 Million Allogeneic hMSCs | Total |
|---|---|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 9.4 | 66.8 years STANDARD_DEVIATION 12.2 | 66.2 years STANDARD_DEVIATION 10.7 |
| Enrollment Ejection Fraction (%) | 26.7 percentage STANDARD_DEVIATION 6.5 | 31.5 percentage STANDARD_DEVIATION 9.9 | 29.1 percentage STANDARD_DEVIATION 8.6 |
| Enrollment Glomerular Filtration Rate (mL/Min) | 79.2 mL/min STANDARD_DEVIATION 20.4 | 70.0 mL/min STANDARD_DEVIATION 24.4 | 74.6 mL/min STANDARD_DEVIATION 22.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 15 Participants | 12 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 1 / 15 |
| other Total, other adverse events | 8 / 15 | 10 / 15 |
| serious Total, serious adverse events | 4 / 15 | 2 / 15 |
Outcome results
Primary
Number of Participants With Treatment-emergent Serious Adverse Events (SAE).
Incidence (at one month post-catheterization) of any treatment-emergent serious adverse events, defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise).
Time frame: One month post-catheterization
Population: SAEs are collected for 12 months, however, outcome 1 is only for SAEs during the first month.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Treatment-emergent Serious Adverse Events (SAE). | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Treatment-emergent Serious Adverse Events (SAE). | 0 Participants |
Secondary
Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level.
Changed in NYHA Functional Classification will be evaluated. Worsened: Documented increase in limitation in physical activity. Improved: Documented decrease in limitation in physical activity. Unchanged: No documented change in limitation in physical activity.
Time frame: Baseline to 3 months, Baseline to 6 months, Baseline to 12 months
Population: Not all participants were able to complete procedure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Unchanged | 10 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 6 months, Worsened | 2 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 6 months, Improved | 5 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 12 months, Improved | 5 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Worsened | 3 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 12 months, Unchanged | 8 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 6 months, Unchanged | 7 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 12 months, Worsened | 1 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Improved | 2 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 12 months, Worsened | 4 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Improved | 4 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Unchanged | 9 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 3 months, Worsened | 2 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 6 months, Improved | 4 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 6 months, Unchanged | 8 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 6 months, Worsened | 2 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 12 months, Improved | 6 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level. | Baseline to 12 months, Unchanged | 4 Participants |
Secondary
Creatinine Kinase Muscle/Brain (CK-MB)
CK-MB values in ng/mL over time.
Time frame: 12 hours, 24 hours post cardiac catheterization
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Creatinine Kinase Muscle/Brain (CK-MB) | 12 hour post catheterization | 3.25 ng/ml |
| Group 1: 20 Million Allogeneic hMSCs | Creatinine Kinase Muscle/Brain (CK-MB) | 24 hour post catheterization | 4.20 ng/ml |
| Group 2: 100 Million Allogeneic hMSCs | Creatinine Kinase Muscle/Brain (CK-MB) | 12 hour post catheterization | 2.45 ng/ml |
| Group 2: 100 Million Allogeneic hMSCs | Creatinine Kinase Muscle/Brain (CK-MB) | 24 hour post catheterization | 4.40 ng/ml |
Secondary
Difference Between Left Ventricular End Diastolic Wall Thickness
As determined by Computed Tomography Scan
Time frame: Baseline, 12 Months
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Difference Between Regional Left Ventricular Function (at the Site of Allogeneic Cell Injections)
As determined by Computed Tomography Scan
Time frame: Baseline, 12 Months
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Difference Between the Left Ventricular Ejection Fraction (LVEF)
Change in 1-year LVEF by CT as compared to baseline.
Time frame: Baseline, 12 months
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Difference Between the Left Ventricular Ejection Fraction (LVEF) | -0.27 Percentage of ejected blood |
| Group 2: 100 Million Allogeneic hMSCs | Difference Between the Left Ventricular Ejection Fraction (LVEF) | 3.00 Percentage of ejected blood |
Secondary
Difference Between the Regional Left Ventricular Wall Thickening
As determined by Computed Tomography Scan
Time frame: Baseline, Month 12
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Difference in Left Ventricular Regional Myocardial Perfusion
As measured via myocardial mass by CT
Time frame: Baseline, 12 months
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Difference in Left Ventricular Volume
Difference in left ventricular end diastolic and end systolic volume will be assessed via ECHO
Time frame: Baseline, 6 months, 12 months
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Difference in Left Ventricular Volume
Difference in left ventricular end diastolic and end systolic volume will be assessed via CT
Time frame: Baseline, 12 months
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Difference in Left Ventricular Volume | 7.65 ml |
| Group 2: 100 Million Allogeneic hMSCs | Difference in Left Ventricular Volume | 3.70 ml |
Secondary
Difference in LVEF
As assessed via ECHO
Time frame: Baseline, 6 months, 12 months
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Echocardiographic-derived Measures of Left Ventricular Function
Left ventricular end diastolic wall thickness as determined by echocardiogram.
Time frame: 6 months, 12 months
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Echocardiographic-derived Measures of Left Ventricular Function | Month 6 | 5.8 centimeters (cm) |
| Group 1: 20 Million Allogeneic hMSCs | Echocardiographic-derived Measures of Left Ventricular Function | Month 12 | 6.1 centimeters (cm) |
| Group 2: 100 Million Allogeneic hMSCs | Echocardiographic-derived Measures of Left Ventricular Function | Month 6 | 6.3 centimeters (cm) |
| Group 2: 100 Million Allogeneic hMSCs | Echocardiographic-derived Measures of Left Ventricular Function | Month 12 | 6.2 centimeters (cm) |
Secondary
Infarct Scar Size (ISS)
Determined by delayed contrast enhanced Computed Tomography (CT) Scan
Time frame: Baseline, 12 months
Population: Not all participants were able to complete procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Infarct Scar Size (ISS) | Baseline | 9.9 Percent of Left Ventricular Mass |
| Group 1: 20 Million Allogeneic hMSCs | Infarct Scar Size (ISS) | 12 Months | 6.8 Percent of Left Ventricular Mass |
| Group 2: 100 Million Allogeneic hMSCs | Infarct Scar Size (ISS) | 12 Months | 5.6 Percent of Left Ventricular Mass |
| Group 2: 100 Million Allogeneic hMSCs | Infarct Scar Size (ISS) | Baseline | 9.7 Percent of Left Ventricular Mass |
Secondary
Minnesota Living With Heart Failure (MLHF) Questionnaire Scores
Minnesota Living with Heart Failure (MLHF) Questionnaire has a total score from 0 to 105. A higher score indicates that participant's heart failure is preventing them from living their life.
Time frame: Baseline, 3 months, 6 months, 12 months
Population: Not all participants were able to complete procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | Baseline | 29.0 score on a scale |
| Group 1: 20 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | 3 months | 22.0 score on a scale |
| Group 1: 20 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | 6 months | 30.0 score on a scale |
| Group 1: 20 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | 12 months | 25.0 score on a scale |
| Group 2: 100 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | 12 months | 15.0 score on a scale |
| Group 2: 100 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | Baseline | 35.0 score on a scale |
| Group 2: 100 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | 6 months | 21.5 score on a scale |
| Group 2: 100 Million Allogeneic hMSCs | Minnesota Living With Heart Failure (MLHF) Questionnaire Scores | 3 months | 20.0 score on a scale |
Secondary
Number of Clinically Significant of Abnormal Lab Values.
Clinical significance of abnormal lab values will be assessed by treating physician
Time frame: 12 months
Population: Data were not available to perform the statistical analyses as described in the protocol for this outcome.
Secondary
Number of Incidents of Major Adverse Cardiac Events (MACE).
Incidence of the Major Adverse Cardiac Events (MACE) endpoint, defined as the composite incidence of (1) death, (2) hospitalization for worsening heart failure, or (3) non-fatal recurrent MI.
Time frame: 1 month, 6 months, 12 months post injection.
Population: Not all participants were able to complete study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Number of Incidents of Major Adverse Cardiac Events (MACE). | 1 month from injection | 0 Incidents |
| Group 1: 20 Million Allogeneic hMSCs | Number of Incidents of Major Adverse Cardiac Events (MACE). | 6 months from injection | 3 Incidents |
| Group 1: 20 Million Allogeneic hMSCs | Number of Incidents of Major Adverse Cardiac Events (MACE). | 12 months from injection | 3 Incidents |
| Group 2: 100 Million Allogeneic hMSCs | Number of Incidents of Major Adverse Cardiac Events (MACE). | 1 month from injection | 0 Incidents |
| Group 2: 100 Million Allogeneic hMSCs | Number of Incidents of Major Adverse Cardiac Events (MACE). | 6 months from injection | 2 Incidents |
| Group 2: 100 Million Allogeneic hMSCs | Number of Incidents of Major Adverse Cardiac Events (MACE). | 12 months from injection | 2 Incidents |
Secondary
Number of Participants With Abnormal ECHO Reading
The number of participants with abnormal reading post-cardiac catheterization. As assessed per treating physician discretion.
Time frame: 6 hours post cardiac catheterization
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal ECHO Reading | Normal | 1 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal ECHO Reading | Abnormal, Not Clinically Significant | 6 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal ECHO Reading | Abnormal, Clinically Significant | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal ECHO Reading | Normal | 2 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal ECHO Reading | Abnormal, Not Clinically Significant | 6 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal ECHO Reading | Abnormal, Clinically Significant | 0 Participants |
Secondary
Number of Participants With Abnormal Electrocardiogram (ECG) Reads.
The number of participants with abnormal ECG readings via 24 hour ambulatory ECG recordings as assessed per treating physician discretion.
Time frame: 12 months
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | baseline, normal | 0 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | baseline, abnormal not clinically significant | 15 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | baseline, abnormal, clinically significant | 0 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months, normal | 0 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months, abnormal not clinically significant | 12 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months, abnormal, clinically significant | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months, abnormal not clinically significant | 14 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | baseline, normal | 1 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months, normal | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | baseline, abnormal not clinically significant | 14 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | 12 months, abnormal, clinically significant | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Abnormal Electrocardiogram (ECG) Reads. | baseline, abnormal, clinically significant | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Event (AE)
Incidence of Treatment Emergent Adverse Event defined as any untoward medical occurrence in a patient or clinical investigation subject temporally associated with the use of the study product.
Time frame: 6 months, 12 months
Population: Not all participants were able to complete the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Treatment Emergent Adverse Event (AE) | Treatment emergent AE (6 month) | 8 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participants With Treatment Emergent Adverse Event (AE) | Treatment emergent AE (12 months) | 10 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Treatment Emergent Adverse Event (AE) | Treatment emergent AE (6 month) | 10 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participants With Treatment Emergent Adverse Event (AE) | Treatment emergent AE (12 months) | 13 Participants |
Secondary
Number of Participant With Reported Tissue Perfusion
Tissue perfusion measured by CT.
Time frame: 6 months, 12 months
Population: Not all participants were able to complete procedure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Number of Participant With Reported Tissue Perfusion | at 6 months | 0 Participants |
| Group 1: 20 Million Allogeneic hMSCs | Number of Participant With Reported Tissue Perfusion | at 12 months | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participant With Reported Tissue Perfusion | at 6 months | 0 Participants |
| Group 2: 100 Million Allogeneic hMSCs | Number of Participant With Reported Tissue Perfusion | at 12 months | 0 Participants |
Secondary
Peak Oxygen Consumption (VO2)
Peak VO2 assessed via treadmill determination.
Time frame: Baseline, 6 months, 12 months
Population: Not all participants were able to complete procedure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Peak Oxygen Consumption (VO2) | Baseline | 15.8 mL/kg/min | Standard Deviation 5.15 |
| Group 1: 20 Million Allogeneic hMSCs | Peak Oxygen Consumption (VO2) | 6 months | 15.0 mL/kg/min | Standard Deviation 5.27 |
| Group 1: 20 Million Allogeneic hMSCs | Peak Oxygen Consumption (VO2) | 12 months | 14.4 mL/kg/min | Standard Deviation 4.94 |
| Group 2: 100 Million Allogeneic hMSCs | Peak Oxygen Consumption (VO2) | Baseline | 16.7 mL/kg/min | Standard Deviation 4.48 |
| Group 2: 100 Million Allogeneic hMSCs | Peak Oxygen Consumption (VO2) | 6 months | 16.5 mL/kg/min | Standard Deviation 5.3 |
| Group 2: 100 Million Allogeneic hMSCs | Peak Oxygen Consumption (VO2) | 12 months | 16.3 mL/kg/min | Standard Deviation 5.84 |
Secondary
Serial Troponin I
Serial Troponin I values in ng/mL over time.
Time frame: 12 hours, 24 hours post cardiac catheterization
Population: Not all participants were able to complete the procedure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Serial Troponin I | 12-hours post-catheterization | 0.01 ng/ml |
| Group 1: 20 Million Allogeneic hMSCs | Serial Troponin I | 24-hours post-catheterization | 0.06 ng/ml |
| Group 2: 100 Million Allogeneic hMSCs | Serial Troponin I | 24-hours post-catheterization | 0.05 ng/ml |
| Group 2: 100 Million Allogeneic hMSCs | Serial Troponin I | 12-hours post-catheterization | 0.01 ng/ml |
Secondary
Six-minute Walk Test.
A test that measures how far a patient can walk in 6 minutes.
Time frame: Baseline, 3 months, 6 months, 12 months
Population: Not all participants were able to complete procedure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: 20 Million Allogeneic hMSCs | Six-minute Walk Test. | Baseline | 398.7 Meters | Standard Deviation 111.62 |
| Group 1: 20 Million Allogeneic hMSCs | Six-minute Walk Test. | 3 months | 396.1 Meters | Standard Deviation 109.62 |
| Group 1: 20 Million Allogeneic hMSCs | Six-minute Walk Test. | 6 months | 416.4 Meters | Standard Deviation 107.76 |
| Group 1: 20 Million Allogeneic hMSCs | Six-minute Walk Test. | 12 months | 409.7 Meters | Standard Deviation 130.19 |
| Group 2: 100 Million Allogeneic hMSCs | Six-minute Walk Test. | 12 months | 463.0 Meters | Standard Deviation 143.07 |
| Group 2: 100 Million Allogeneic hMSCs | Six-minute Walk Test. | Baseline | 434.9 Meters | Standard Deviation 120.04 |
| Group 2: 100 Million Allogeneic hMSCs | Six-minute Walk Test. | 6 months | 453.6 Meters | Standard Deviation 126.82 |
| Group 2: 100 Million Allogeneic hMSCs | Six-minute Walk Test. | 3 months | 433.5 Meters | Standard Deviation 133.97 |