Stem Cell Transplantation, Ventricular Dysfunction, Left
Conditions
Keywords
Chronic Ischemic Left Ventricular Dysfunction
Brief summary
Heart attacks are a leading cause of death in both men and women in the United States. When a person has a heart attack, blood is unable to reach a certain area of the heart, and if the blood supply is not re-established quickly, that area of the heart can suffer permanent damage. While recovery from a heart attack can be managed through medications and lifestyle changes, these treatments can not reverse the original damage to the heart. Current research is focusing on the development of cell-based therapies using stem cells to repair organs that have been irreversibly damaged by disease. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair. This study will evaluate the safety and effectiveness of injecting MSCs into the heart to repair and restore heart function in people who have had a heart attack and who are having heart surgery for coronary artery bypass grafting (CABG).
Detailed description
Participation in this study will last 18 months. Potential participants will undergo initial screening 5 to 7 weeks prior to CABG surgery. Screening will include a physical exam, blood draw, pregnancy test, questions about medical history, current medications, and alcohol or drug use, an electrocardiogram (ECG), magnetic resonance imaging (MRI) of the heart, questionnaires, an echocardiogram and a computed tomography (CT) scan. Eligible participants will then undergo two baseline visits within 6 weeks of their scheduled surgery. Baseline Visit 1 will consist of vital sign measurements, a bone marrow aspiration to obtain MSCs and a blood draw for a biomarker test. Baseline Visit 2 will include treadmill test, 6-minute walk test, pulmonary function (FEV1) study and a 48 Hour Ambulatory ECG. After the second baseline visit, participants will be assigned randomly to receive either MSCs or placebo after surgery. On the day of surgery, once all of the bypass grafts have been placed, a high or low dose of MSCs or placebo will be injected into a damaged area of the heart that did not receive a bypass graft. After receiving the injections, participants will remain in the hospital for up to 7 days. During this stay, participants will undergo a daily blood draw, urine test, ECG, and ambulatory ECG monitoring for the first 96 hours after surgery. Upon being discharged, participants will return for monthly visits for 6 months and for follow-up visits 12 and 18 months after surgery. These visits will repeat most initial screening and baseline tests. There will be one additional visit 14 days after surgery, which will include questions about side effects, a physical exam, and a 48-hour ambulatory ECG.
Interventions
BIOLOGICALLower dose mesenchymal stem cell (MSC) injection
Participants will receive between 10 and 20 intramyocardial injections of 2 million MSCs per 0.25-0.5 cubic centimeter (cc) for a total of 2 x 10\^7 cells. The injections will be administered following completion of CABG surgery.
GENETICPlacebo
Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).
BIOLOGICALHigher dose MSC injection
Participants will receive between 10 and 20 intramyocardial injections of 20 million MSCs per 0.25-0.5 cc for a total of 2 x 10\^8 cells. The injections will be administered following completion of CABG surgery.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University Specialized Center for Cell Based Therapy
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic ischemic heart failure caused by a heart attack * Scheduled to undergo cardiac surgery for CABG * Ejection fraction between 15% and 50% * Presence of an akinetic or dyskinetic region by standard imaging
Exclusion criteria
* Glomerular filtration rate of less than 50 mL/min/1.73m2 at study entry * Contraindication to performance of an MRI scan * Bone marrow dysfunction, as evidenced by a 20% or more deviation from normal hematocrit, white blood cell count, or platelet values without another explanation * A coagulopathy condition not due to a reversible cause (i.e., Coumadin) * Known, serious radiographic contrast allergy * Known allergies to penicillin or streptomycin * Organ transplant recipient * Clinical history of malignancy within 5 years of study entry (e.g., patients with prior malignancy must be disease free for 5 years), except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma * Non-cardiac condition that limits lifespan to less than 1 year * On chronic therapy with immunosuppressant medication * Serum positive for HIV, hepatitis B, or hepatitis C * Female who is pregnant, nursing, or of child-bearing potential and not practicing effective birth control methods
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Serious Adverse Events | 12 Months | Six-month post-CABG surgery serious adverse event (SAE) proportion of patients experiencing a composite of sustained ventricular arrhythmias, (lasting longer than 15 seconds), with hemodynamic compromise, sudden unexpected death at six months, ectopic tissue formation at 12 months by chest/abdomen/pelvis CT exam. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Function (LVF) in Region of MSC Injection | Assessed at Baseline and 18 Months | The Left Ventricular Function differences in the region of MSC injection were evaluated. LVF is evaluated via ECHO as the percentage of ejected blood. |
| Regional Left Ventricular Wall Thickening | Assessed at Baseline and 18 months | Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI. |
| Left Ventricular End Diastolic Wall Thickness | Assessed at Baseline and 18 months | Difference between the baseline and 18 month left ventricular end diastolic wall thickness as determined by MRI and echocardiogram. |
| Change in Left Ventricular End Diastolic and Systolic Volume | Baseline, 6 Months, 18 Months | Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram. |
| Change in Left Ventricular Ejection Fraction | Baseline to 6 Months, Baseline to 18 Months | Change between baseline to 6-month and 18-month left ventricular ejection fraction (LVEF) as determined by MRI and echocardiogram. |
| Change in Peak Volume Oxygen | Baseline, 6 Months, 18 Months | Change in Peak VO2 as determined by treadmill test (mL/mg/min) from Baseline to 6 and from baseline to 18 months |
| Change in Six Minute Walk Test | Baseline, 6 Months, 18 Months | Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months |
| Change in NYHA Functional Class | Baseline to 6 Months, 6 months to 18 Months | Change in New York Heart Association (NYHA) Functional Classification based on patient's self reported activity level. Worsened: documented increase in limitations of physical activity as self-described by subject Improved: documented decrease in limitations of physical activity as self-described by subject Unchanged: no documented change in limitations of physical activity as self-described by subject |
| Change in Infarct Scar Size (ISS) Over 18 Month Period | Baseline, 6 Months, 18 Months | Change in infarct scar size (ISS) between baseline and 6-month and 18 month visits as determined by delayed contrast-enhanced MRI. |
| Incidence of Major Adverse Cardiac Events (MACE) | 18 Months | Incidence of Major Adverse Cardiac Events (MACE). A composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent Ml. |
| Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | Assessed at 6 Months, 12 Months, and 18 Months | Ambulatory ECG monitoring is the most widely employed technology for the evaluation of a patient with symptoms suggestive of cardiac arrhythmia or conduction abnormality. When the patient returns for follow up the 48- Hour Ambulatory monitor provides the data to the site staff to detect any abnormal recordings based upon standard ECG protocol. |
| Change in Pulmonary Function | Baseline, 6 Months, 12 Months, 18 Months | Change in Pulmonary Function from Baseline to 6 month, Baseline to 12 month, and Baseline to 18 month visits as measured by forced expiratory volume in 1 second (FEV1) |
| Serial Troponin Values (ng/mL) | Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG | Serial Troponin Values (ng/mL) Values from Baseline to 48 Hours Post CABG |
| Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG | Creatinine Kinase MB (ng/mL) Values every 12 hours from Baseline to 48 Hours Post CABG |
| Number of Clinically Significant Laboratory Values | 18 Months | Clinically significant laboratory values are first determined via standard laboratory normal values from a CAP and CLIA certified Laboratory and then assessed by investigator based on specific patient conditions and disease state. |
| Rate of Treatment Emergent Adverse Events | Assessed at 6 Months, 12 Months, and 18 Months | Rate of Treatment Emergent Adverse Events Post Coronary Artery Bypass Graft (CABG) at 6 Months, 12 Months, and 18 Months |
| Number of Abnormal Echocardiogram Readings 2 Days Post CABG. | Day 2 | The number of abnormal Echocardiogram readings 2 Days Post CABG will be documented based on transthoracic Echocardiographic standards. However, although Echocardiograms 2 days post CABG operation may show abnormalities which is standard in this population, this testing is instrumental because it measures End- diastolic wall thickness and Left ventricular volumes at end-diastole and end-systole. |
| Minnesota Living With Heart Failure Questionnaire Scores | Assessed at 6 Months and 18 Months | Minnesota Living with Heart Failure (MLHF) questionnaire has a total score from 0 to 105. A higher score indicates that participants heart failure is preventing them from living their lives measured at two time points. |
Countries
United States
Participant flow
Pre-assignment details
This trial, which originally was designed to enroll 45 patients, was suspended after 9 patients were enrolled because of slow accrual.
Participants by arm
| Arm | Count |
|---|---|
| (1) Lower MSC Dose Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 107 cells
Lower dose mesenchymal stem cell (MSC) injection: Participants will receive between 10 and 20 intramyocardial injections of 2 million MSCs per 0.25-0.5 cubic centimeter (cc) for a total of 2 x 107 cells. The injections will be administered following completion of CABG surgery. | 2 |
| (2) Higher MSC Dose Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 108 cells
Higher dose MSC injection: Participants will receive between 10 and 20 intramyocardial injections of 20 million MSCs per 0.25-0.5 cc for a total of 2 x 108 cells. The injections will be administered following completion of CABG surgery. | 4 |
| (3) Placebo Participants will receive placebo injections
Placebo: Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA). | 3 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | (1) Lower MSC Dose | (2) Higher MSC Dose | (3) Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 60.3668720 years STANDARD_DEVIATION 13.4742319 | 51.9240246 years STANDARD_DEVIATION 9.1760352 | 63.6276523 years STANDARD_DEVIATION 2.9733072 | 57.7014222 years STANDARD_DEVIATION 9.386946 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 | 1 / 3 |
| other Total, other adverse events | 2 / 2 | 4 / 4 | 2 / 3 |
| serious Total, serious adverse events | 0 / 2 | 2 / 4 | 3 / 3 |
Outcome results
Primary
Number of Patients With Serious Adverse Events
Six-month post-CABG surgery serious adverse event (SAE) proportion of patients experiencing a composite of sustained ventricular arrhythmias, (lasting longer than 15 seconds), with hemodynamic compromise, sudden unexpected death at six months, ectopic tissue formation at 12 months by chest/abdomen/pelvis CT exam.
Time frame: 12 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treated Group (Low/High Doses) | Number of Patients With Serious Adverse Events | 0 Participants |
| Placebo Group | Number of Patients With Serious Adverse Events | 1 Participants |
Secondary
Change in Infarct Scar Size (ISS) Over 18 Month Period
Change in infarct scar size (ISS) between baseline and 6-month and 18 month visits as determined by delayed contrast-enhanced MRI.
Time frame: Baseline, 6 Months, 18 Months
Population: One placebo subject expired Day 3 post injection. Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in Infarct Scar Size (ISS) Over 18 Month Period | 6 Months | -2.37 Grams (g) |
| Treated Group (Low/High Doses) | Change in Infarct Scar Size (ISS) Over 18 Month Period | 18 Months | -5.91 Grams (g) |
| Placebo Group | Change in Infarct Scar Size (ISS) Over 18 Month Period | 6 Months | -2.16 Grams (g) |
| Placebo Group | Change in Infarct Scar Size (ISS) Over 18 Month Period | 18 Months | -5.32 Grams (g) |
Secondary
Change in Left Ventricular Ejection Fraction
Change between baseline to 6-month and 18-month left ventricular ejection fraction (LVEF) as determined by MRI and echocardiogram.
Time frame: Baseline to 6 Months, Baseline to 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in Left Ventricular Ejection Fraction | Baseline to 6 Months | -.34 percentage of Ejection Fraction |
| Treated Group (Low/High Doses) | Change in Left Ventricular Ejection Fraction | Baseline to 18 Months | 2.50 percentage of Ejection Fraction |
| Placebo Group | Change in Left Ventricular Ejection Fraction | Baseline to 6 Months | 13.18 percentage of Ejection Fraction |
| Placebo Group | Change in Left Ventricular Ejection Fraction | Baseline to 18 Months | 14.61 percentage of Ejection Fraction |
Secondary
Change in Left Ventricular End Diastolic and Systolic Volume
Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram.
Time frame: Baseline, 6 Months, 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in Left Ventricular End Diastolic and Systolic Volume | End Diastolic Volume from Baseline to 6 Months | 192.92 ml |
| Treated Group (Low/High Doses) | Change in Left Ventricular End Diastolic and Systolic Volume | End Systolic Volume from Baseline to 6 Months | 130.09 ml |
| Treated Group (Low/High Doses) | Change in Left Ventricular End Diastolic and Systolic Volume | End Diastolic from 6 Month to 18 Month | 218.73 ml |
| Treated Group (Low/High Doses) | Change in Left Ventricular End Diastolic and Systolic Volume | End Systolic from 6 Month to 18 Month | 135.99 ml |
| Placebo Group | Change in Left Ventricular End Diastolic and Systolic Volume | End Systolic from 6 Month to 18 Month | 94.90 ml |
| Placebo Group | Change in Left Ventricular End Diastolic and Systolic Volume | End Diastolic Volume from Baseline to 6 Months | 169.63 ml |
| Placebo Group | Change in Left Ventricular End Diastolic and Systolic Volume | End Diastolic from 6 Month to 18 Month | 172.01 ml |
| Placebo Group | Change in Left Ventricular End Diastolic and Systolic Volume | End Systolic Volume from Baseline to 6 Months | 97.13 ml |
Secondary
Change in NYHA Functional Class
Change in New York Heart Association (NYHA) Functional Classification based on patient's self reported activity level. Worsened: documented increase in limitations of physical activity as self-described by subject Improved: documented decrease in limitations of physical activity as self-described by subject Unchanged: no documented change in limitations of physical activity as self-described by subject
Time frame: Baseline to 6 Months, 6 months to 18 Months
Population: Due to the early termination of the study,there was an insufficient sample size of the MSC treated participants.The statistical analysis plan was revised to combine the low and high dose groups.1 treated subject's NYHA class was not captured at the 18 Month time point.1 placebo treated subject expired prior to 6 and 18 months NYHA class assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in NYHA Functional Class | Baseline to 6 Months, Worsened | 0 Participants |
| Treated Group (Low/High Doses) | Change in NYHA Functional Class | Baseline to 6 Months, Improved | 3 Participants |
| Treated Group (Low/High Doses) | Change in NYHA Functional Class | Baseline to 6 Months, Unchanged | 3 Participants |
| Treated Group (Low/High Doses) | Change in NYHA Functional Class | 6 Months to 18 Months, Worsened | 2 Participants |
| Treated Group (Low/High Doses) | Change in NYHA Functional Class | 6 Months to 18 Months, Improved | 0 Participants |
| Treated Group (Low/High Doses) | Change in NYHA Functional Class | 6 Months to 18 Months, Unchanged | 3 Participants |
| Placebo Group | Change in NYHA Functional Class | 6 Months to 18 Months, Improved | 1 Participants |
| Placebo Group | Change in NYHA Functional Class | Baseline to 6 Months, Worsened | 0 Participants |
| Placebo Group | Change in NYHA Functional Class | 6 Months to 18 Months, Worsened | 0 Participants |
| Placebo Group | Change in NYHA Functional Class | Baseline to 6 Months, Improved | 1 Participants |
| Placebo Group | Change in NYHA Functional Class | 6 Months to 18 Months, Unchanged | 1 Participants |
| Placebo Group | Change in NYHA Functional Class | Baseline to 6 Months, Unchanged | 1 Participants |
Secondary
Change in Peak Volume Oxygen
Change in Peak VO2 as determined by treadmill test (mL/mg/min) from Baseline to 6 and from baseline to 18 months
Time frame: Baseline, 6 Months, 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in Peak Volume Oxygen | Baseline to 6 Months | .2 (mL/mg/min) |
| Treated Group (Low/High Doses) | Change in Peak Volume Oxygen | Baseline to 18 Months | -.2 (mL/mg/min) |
| Placebo Group | Change in Peak Volume Oxygen | Baseline to 6 Months | -.2 (mL/mg/min) |
| Placebo Group | Change in Peak Volume Oxygen | Baseline to 18 Months | -.4 (mL/mg/min) |
Secondary
Change in Pulmonary Function
Change in Pulmonary Function from Baseline to 6 month, Baseline to 12 month, and Baseline to 18 month visits as measured by forced expiratory volume in 1 second (FEV1)
Time frame: Baseline, 6 Months, 12 Months, 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in Pulmonary Function | Baseline to 6 Months | -7.2 Liters |
| Treated Group (Low/High Doses) | Change in Pulmonary Function | Baseline to 12 Months | -8.5 Liters |
| Treated Group (Low/High Doses) | Change in Pulmonary Function | Baseline to 18 Months | -7.2 Liters |
| Placebo Group | Change in Pulmonary Function | Baseline to 18 Months | 7.5 Liters |
| Placebo Group | Change in Pulmonary Function | Baseline to 6 Months | 7.0 Liters |
| Placebo Group | Change in Pulmonary Function | Baseline to 12 Months | -5.5 Liters |
Secondary
Change in Six Minute Walk Test
Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months
Time frame: Baseline, 6 Months, 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Change in Six Minute Walk Test | Baseline to 6 Months | 67 Meters |
| Treated Group (Low/High Doses) | Change in Six Minute Walk Test | Baseline to 18 Months | 67 Meters |
| Placebo Group | Change in Six Minute Walk Test | Baseline to 6 Months | -30.00 Meters |
| Placebo Group | Change in Six Minute Walk Test | Baseline to 18 Months | -33.0 Meters |
Secondary
Creatinine Kinase - Muscle/Brain (MB) (ng/mL)
Creatinine Kinase MB (ng/mL) Values every 12 hours from Baseline to 48 Hours Post CABG
Time frame: Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 48H | 4.75 ng/mL |
| Treated Group (Low/High Doses) | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | Baseline | 2.2 ng/mL |
| Treated Group (Low/High Doses) | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 12H | 19.6 ng/mL |
| Treated Group (Low/High Doses) | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 24H | 12.39 ng/mL |
| Treated Group (Low/High Doses) | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 36H | 8.04 ng/mL |
| Placebo Group | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 36H | 8.1 ng/mL |
| Placebo Group | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 24H | 15.5 ng/mL |
| Placebo Group | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | Baseline | 2.6 ng/mL |
| Placebo Group | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 48H | 6 ng/mL |
| Placebo Group | Creatinine Kinase - Muscle/Brain (MB) (ng/mL) | 12H | 24.75 ng/mL |
Secondary
Incidence of Major Adverse Cardiac Events (MACE)
Incidence of Major Adverse Cardiac Events (MACE). A composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent Ml.
Time frame: 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated Group (Low/High Doses) | Incidence of Major Adverse Cardiac Events (MACE) | 0 # of Major Adverse Cardiac Events (MACE) |
| Placebo Group | Incidence of Major Adverse Cardiac Events (MACE) | 1 # of Major Adverse Cardiac Events (MACE) |
Secondary
Left Ventricular End Diastolic Wall Thickness
Difference between the baseline and 18 month left ventricular end diastolic wall thickness as determined by MRI and echocardiogram.
Time frame: Assessed at Baseline and 18 months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treated Group (Low/High Doses) | Left Ventricular End Diastolic Wall Thickness | Baseline | 5.86 mm | Standard Error 0.46 |
| Treated Group (Low/High Doses) | Left Ventricular End Diastolic Wall Thickness | 18 Months | 6.17 mm | Standard Error 0.48 |
| Placebo Group | Left Ventricular End Diastolic Wall Thickness | Baseline | 16.15 mm | Standard Error 2.72 |
| Placebo Group | Left Ventricular End Diastolic Wall Thickness | 18 Months | 18.54 mm | Standard Error 1.55 |
Secondary
Left Ventricular Function (LVF) in Region of MSC Injection
The Left Ventricular Function differences in the region of MSC injection were evaluated. LVF is evaluated via ECHO as the percentage of ejected blood.
Time frame: Assessed at Baseline and 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treated Group (Low/High Doses) | Left Ventricular Function (LVF) in Region of MSC Injection | Baseline | -15.26 percentage of ejected blood | Standard Error 3.15 |
| Treated Group (Low/High Doses) | Left Ventricular Function (LVF) in Region of MSC Injection | 18 Months | -21.13 percentage of ejected blood | Standard Error 1.68 |
| Placebo Group | Left Ventricular Function (LVF) in Region of MSC Injection | Baseline | -18.53 percentage of ejected blood | Standard Error 2.71 |
| Placebo Group | Left Ventricular Function (LVF) in Region of MSC Injection | 18 Months | -19.66 percentage of ejected blood | Standard Error 1.07 |
Secondary
Minnesota Living With Heart Failure Questionnaire Scores
Minnesota Living with Heart Failure (MLHF) questionnaire has a total score from 0 to 105. A higher score indicates that participants heart failure is preventing them from living their lives measured at two time points.
Time frame: Assessed at 6 Months and 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Minnesota Living With Heart Failure Questionnaire Scores | 6 Month Visit | 11.5 score on a scale |
| Treated Group (Low/High Doses) | Minnesota Living With Heart Failure Questionnaire Scores | 18 Month Visit | 7.3 score on a scale |
| Placebo Group | Minnesota Living With Heart Failure Questionnaire Scores | 6 Month Visit | 54.5 score on a scale |
| Placebo Group | Minnesota Living With Heart Failure Questionnaire Scores | 18 Month Visit | 10.5 score on a scale |
Secondary
Number of Abnormal Echocardiogram Readings 2 Days Post CABG.
The number of abnormal Echocardiogram readings 2 Days Post CABG will be documented based on transthoracic Echocardiographic standards. However, although Echocardiograms 2 days post CABG operation may show abnormalities which is standard in this population, this testing is instrumental because it measures End- diastolic wall thickness and Left ventricular volumes at end-diastole and end-systole.
Time frame: Day 2
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine dose groups to make a comparison to placebo subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated Group (Low/High Doses) | Number of Abnormal Echocardiogram Readings 2 Days Post CABG. | 6 Abnormal Echocardiograms |
| Placebo Group | Number of Abnormal Echocardiogram Readings 2 Days Post CABG. | 3 Abnormal Echocardiograms |
Secondary
Number of Clinically Significant Laboratory Values
Clinically significant laboratory values are first determined via standard laboratory normal values from a CAP and CLIA certified Laboratory and then assessed by investigator based on specific patient conditions and disease state.
Time frame: 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Number of Clinically Significant Laboratory Values | Clinically Significant Hematology Values | 6 Incidents |
| Treated Group (Low/High Doses) | Number of Clinically Significant Laboratory Values | Clinically Significant Clinical Chemistry Values | 9 Incidents |
| Treated Group (Low/High Doses) | Number of Clinically Significant Laboratory Values | Clinically Significant Urinalysis Values | 0 Incidents |
| Placebo Group | Number of Clinically Significant Laboratory Values | Clinically Significant Clinical Chemistry Values | 0 Incidents |
| Placebo Group | Number of Clinically Significant Laboratory Values | Clinically Significant Hematology Values | 0 Incidents |
| Placebo Group | Number of Clinically Significant Laboratory Values | Clinically Significant Urinalysis Values | 0 Incidents |
Secondary
Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings
Ambulatory ECG monitoring is the most widely employed technology for the evaluation of a patient with symptoms suggestive of cardiac arrhythmia or conduction abnormality. When the patient returns for follow up the 48- Hour Ambulatory monitor provides the data to the site staff to detect any abnormal recordings based upon standard ECG protocol.
Time frame: Assessed at 6 Months, 12 Months, and 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo. One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | 6 Month Visit | 4 Participants |
| Treated Group (Low/High Doses) | Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | 12 Month Visit | 3 Participants |
| Treated Group (Low/High Doses) | Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | 18 Month Visit | 5 Participants |
| Placebo Group | Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | 6 Month Visit | 2 Participants |
| Placebo Group | Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | 12 Month Visit | 2 Participants |
| Placebo Group | Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings | 18 Month Visit | 2 Participants |
Secondary
Rate of Treatment Emergent Adverse Events
Rate of Treatment Emergent Adverse Events Post Coronary Artery Bypass Graft (CABG) at 6 Months, 12 Months, and 18 Months
Time frame: Assessed at 6 Months, 12 Months, and 18 Months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Rate of Treatment Emergent Adverse Events | 6 Months Post CABG | 9.5 Number of Adverse Events |
| Treated Group (Low/High Doses) | Rate of Treatment Emergent Adverse Events | 12 Months Post CABG | 10.0 Number of Adverse Events |
| Treated Group (Low/High Doses) | Rate of Treatment Emergent Adverse Events | 18 Months Post CABG | 11 Number of Adverse Events |
| Placebo Group | Rate of Treatment Emergent Adverse Events | 6 Months Post CABG | 5.0 Number of Adverse Events |
| Placebo Group | Rate of Treatment Emergent Adverse Events | 12 Months Post CABG | 5.7 Number of Adverse Events |
| Placebo Group | Rate of Treatment Emergent Adverse Events | 18 Months Post CABG | 6 Number of Adverse Events |
Secondary
Regional Left Ventricular Wall Thickening
Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI.
Time frame: Assessed at Baseline and 18 months
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.One placebo subject expired Day 3 post injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treated Group (Low/High Doses) | Regional Left Ventricular Wall Thickening | Baseline | 20.68 mm | Standard Error 6.67 |
| Treated Group (Low/High Doses) | Regional Left Ventricular Wall Thickening | 18 Months | 47.87 mm | Standard Error 9.45 |
| Placebo Group | Regional Left Ventricular Wall Thickening | Baseline | 32.21 mm | Standard Error 9.97 |
| Placebo Group | Regional Left Ventricular Wall Thickening | 18 Months | 42.09 mm | Standard Error 9.49 |
Secondary
Serial Troponin Values (ng/mL)
Serial Troponin Values (ng/mL) Values from Baseline to 48 Hours Post CABG
Time frame: Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG
Population: Due to the early termination of the study, there was an insufficient sample size of the Low and High dose of MSCs participants. The statistical analysis plan was revised to combine the low and high dose groups in order to make a comparison to the participants who received a placebo.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treated Group (Low/High Doses) | Serial Troponin Values (ng/mL) | 12H | .76 ng/mL |
| Treated Group (Low/High Doses) | Serial Troponin Values (ng/mL) | 36H | .55 ng/mL |
| Treated Group (Low/High Doses) | Serial Troponin Values (ng/mL) | 24H | .35 ng/mL |
| Treated Group (Low/High Doses) | Serial Troponin Values (ng/mL) | 48H | .21 ng/mL |
| Treated Group (Low/High Doses) | Serial Troponin Values (ng/mL) | Baseline | .01 ng/mL |
| Placebo Group | Serial Troponin Values (ng/mL) | 48H | .2 ng/mL |
| Placebo Group | Serial Troponin Values (ng/mL) | Baseline | .01 ng/mL |
| Placebo Group | Serial Troponin Values (ng/mL) | 12H | .76 ng/mL |
| Placebo Group | Serial Troponin Values (ng/mL) | 24H | .1 ng/mL |
| Placebo Group | Serial Troponin Values (ng/mL) | 36H | .36 ng/mL |