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Heart Failure has several etiologies and one of them is coronary artery disease. Coronary artery bypass grafting (CABG) is one of revascularizations method which has been used for decades in coronary artery disease theraphy. However, data about coronary artery bypass grafting shows that post-CABG patients still have low ejection fraction. For the last decade, there have been a lot of studies about the using of stem cells to increase heart contractility and reverse the heart remodelling process. In this study, we use CD 133+ bone marrow stem cells which has been proved to have higher angiogenesis potential. The stem cells is given during CABG by injection transepicardial and transseptal. The purpose of this study is to determine whether transpicardial and transseptal injection of CD 133+ bone marrow stem cells can improve myocardial perfusion in patient with low ejection fraction following CABG surgery.
Study sample : patient with low ejection fraction indicated for CABG surgery in NCCHK who fulfill inclusion and exclusion criteria
Sampling method : first we use consecutive method to find subject with male sex and age 40-70. After that, we use simple random sampling to allocate each subject to each group.
Total samples is 13 for each group. To anticipated drop out rate 10%, total sample is 15 for each group.
Intervention and measurement :
Control group will only receive CABG surgery. Study group will receive CBAG surgery and stem cell implantation. Stem cell aspiration will be performed 1 day before CABG procedure. Before aspiration, patients will be given local anesthetic and light sedation. Stem cell will be collected from posterior iliac crest. Total aspirate 190 cc. Stem cell CD133+ will be separated using CliniMACS® Magnetic Separation Device after labelled with Magnetic microbeads - anti CD133 labelling.
Myocardial perfusion reserve index will be measure using MRI. MPRI value will be obtained globally and segmentally in each 16 ventricle segments VEGF plasma level will be measured using sandwich Enzyme-linked Immunosorbent Assay method.
Ejection fraction, left ventricle dimension, and scar size will be measured using MRI.
Quality of life will be measured using Minnesota Living With Heart Failure Questionnaire.
Statistical analysis is done using IBM SPSS Statistics version 21.0 (SPSS inc, Chicago, IL, USA). Numerical data will be presented in either mean/standard deviation or median/min-max depend on distribution of data. Hypothesis test for numeric variable is done using paired/non-paired T test or Mann-Whitney/Wilcoxon depend on normality of data. Normality test is done using Shapiro-Wilk test. Hypothesis test for category varible is done using chi-square or fischer test.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| subject | Experimental | this arm will receive Transepicardial with Transseptal CD 133+ Implantation |
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| control | No Intervention | this arm will not receive Transepicardial with Transseptal CD 133+ Implantation |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transepicardial with Transseptal CD 133+ Implantation | Biological | Transepicardial with Transseptal CD 133+ Implantation |
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| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Defect Perfusion | Number of heart wall segments with perfusion defect measured by MRI. | Baseline, 6 months |
| Left Ventricular Ejection Fraction | Left ventricular ejection fraction (LVEF) measured by MRI. Normal range of LVEF ranges from 50% to 70%. Borderline LVEF ranges from 41% to 49% Reduced LVEF ranges < 41% | Baseline, 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Six Minutes Walking Test | Quality of life will be assessed using Six minutes walking test, to see the changes of six minutes walking test before and after intervention Distances reported for healthy individuals ages 40 yo 85 years range from 400 to 700 m.. | Baseline, 6 months |
| Wall Motion Score Index |
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Inclusion Criteria:
Exclusion Criteria:
Emergency CABG Ungraftable coronary artery Acute myocardial Infarct (<14 days) Valve disease which need surgery repair Contraindicated for MRI High degree ventricular arrhytmia Coagulation disorder HIV positive patient, Hepatitis B + patients, HCV + patients AST/ALT > 1,5 upper normal value Creatinine > 2 g/dl. Malignancy
Drop out criteria :
Aortic cross clamp >120 minutes and CABG total time >180
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| Name | Affiliation | Role |
|---|---|---|
| Tri Wisesa Soetisna, MD, MHA | National Cardiovascular Center Harapan Kita | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cardiovascular Center Harapan Kita | Jakarta | DKI Jakarta | 11420 | Indonesia |
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| ID | Title | Description |
|---|---|---|
| FG000 | CABG + Transepicardial With Transseptal CD 133+ Implantation | this arm will receive CABG + Transepicardial with Transseptal CD 133+ Implantation |
| FG001 | Control | this arm will receive CABG only |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 25, 2020 |
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Cardiac wall motion abnormality will be measured using Wall Motion Score Index with MRI. Each myocardial segment is assigned a score from 1 to 4. The 16 segment model of myocardial segmentation is recommended. A WMSI of 1.0 is considered normokinetic. A WMSI of 1.5 is considered mild hypokinesia A WMSI of 2.0 is considered hypokinesia A WMSI of 2.5 is considered severe hypokinesia A WMSI of 3.0 is considered akinetic. |
| Baseline, 6 months |
| Myocardial Scar Size | Percentage of myocardial scar size proportion measured by MRI to quantify and define the extent/transmurality of scar tissue, the following definitions were used
| Baseline, 6 months |
| Vascular Endothelial Growth Factor | Cytokine that has important role for angiogenesis. Normal range for plasma VEGF is 0-115 pg/ml | Baseline, 6 months |
| Left Ventricle End Systolic Volume | Left ventricle end-systolic volume is the volume of blood in a left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. Normal LVESV ranges is 37 - 57 mililiters. | Baseline, 6 months |
| Minnesota Living With Heart Failure Questionnaire | Quality of life assessed using Minnesota Living With Heart Failure Questionnaire consist of 21 questions, to see the changes before and after intervention. Minimum score = 0, Maximum score = 105 Higher values represent a worse outcome | Baseline, 6 months |
| Left Ventricle End Diastolic Volume | Left ventricle end-diastolic volume is the volume of blood in the left ventricle at end load or filling in (diastole) or the amount of blood in the ventricle just before systole. Normal ranges of LVEDV is 121 - 163 mililiters | Baseline, 6 months |
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| ID | Title | Description |
|---|---|---|
| BG000 | CABG + Transepicardial With Transseptal CD 133+ Implantation | this arm will receive Transepicardial with Transseptal CD 133+ Implantation |
| BG001 | Control | this arm will not receive Transepicardial with Transseptal CD 133+ Implantation |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Systolic blood pressure | Systolic blood pressure is created when the heart beats, squeezes and push blood through arteries. The unit of measure is mmHg. Normal range for systolic pressure is < 120 mmHg | Mean | Standard Deviation | mmHg |
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| Diastolic blood pressure | Pressure blood exerts within arteries between heart beats. Normal range for diastolic pressure is < 80 mmHg | Mean | Standard Deviation | mmHg |
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| Smoking | Smoking as one of coronary artery disease risk factor. | Count of Participants | Participants |
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| Dyslipidemia | Dyslipidemia as one of coronary artery disease risk factor. | Count of Participants | Participants |
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| Hypertension | Hypertension as one of coronary artery disease risk factor. | Count of Participants | Participants |
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| Menopause | Menopause as one of coronary artery disease risk factor. | Count of Participants | Participants |
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| Diabetes | Diabetes as one of coronary artery disease risk factor. | Count of Participants | Participants |
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| Random blood sugar level | The reference values for a "normal" random glucose test in an average adult are 80-140 mg/dl, between 140-2000 mg/dl is considered pre-diabetis, and >200 mg/dl is considered diabetes according ADA guidelines. | Mean | Standard Deviation | mg/dl |
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| NYHA grade III-IV | NYHA (New York Heart Association) is classification for heart failure. Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. | Count of Participants | Participants |
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| CCS grade III-IV | Canadian Cardiovascular Society grading of angina pectoris. I : Ordinary physical activity does not cause angina II: Slight limitation of ordinary activity III: Marked limitation of ordinary physical activity IV: Inability to carry on any physical activity without discomfort, anginal syndrome may be present at rest | Count of Participants | Participants |
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| Six minutes walk test | 6-min walk test is sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. | Mean | Standard Deviation | meters |
| ||||||||||||||
| Left Ventricle Ejection Fraction | Left ventricular ejection fraction (LVEF) measured by MRI. Normal range of LVEF ranges from 50% to 70%. Borderline LVEF ranges from 41% to 49% Reduced LVEF ranges < 41% | Mean | Standard Deviation | Percentage of Ejection Fraction |
| ||||||||||||||
| Left Ventricle End-Systolic Volume | Left ventricle end-systolic volume is the volume of blood in a left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. Normal LVESV ranges is 37 - 57 mililiters. | Mean | Standard Deviation | mililiters |
| ||||||||||||||
| Left Ventricle End-Diastolic Volume | Left ventricle end-diastolic volume is the volume of blood in the left ventricle at end load or filling in (diastole) or the amount of blood in the ventricle just before systole. Normal ranges of LVEDV is 121 - 163 mililiters | Mean | Standard Deviation | mililiters |
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| Myocardial Scar Size | Percentage of myocardial scar size proportion measured by MRI to quantify and define the extent/transmurality of scar tissue, the following definitions were used
| Mean | Standard Deviation | Percentage of Scar Area |
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| Myocardial perfusion defect | Number of heart wall segments with perfusion defect measured by MRI. | Mean | Standard Deviation | Percentage of Myocardial Perfusion |
| ||||||||||||||
| Wall motion score index | Cardiac wall motion abnormality will be measured using Wall Motion Score Index with MRI. Each myocardial segment is assigned a score from 1 to 4. The 16 segment model of myocardial segmentation is recommended. A WMSI of 1.0 is considered normokinetic. A WMSI of 1.5 is considered mild hypokinesia A WMSI of 2.0 is considered hypokinesia A WMSI of 2.5 is considered severe hypokinesia A WMSI of 3.0 is considered akinetic. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Minnesotta Living with Heart Failure Score | Quality of life assessed using Minnesota Living With Heart Failure Questionnaire consist of 21 questions, to see the changes before and after intervention. Minimum score = 0, Maximum score = 105 Higher values represent a worse outcome | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Vascular Endothelial Growth Factor | Cytokine that has important role for angiogenesis. Normal range for plasma VEGF is 0-115 pg/ml | Mean | Standard Deviation | pg/mL |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Myocardial Defect Perfusion | Number of heart wall segments with perfusion defect measured by MRI. | Posted | Mean | Standard Deviation | Percentage of Myocardial Perfusion | Baseline, 6 months |
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| Primary | Left Ventricular Ejection Fraction | Left ventricular ejection fraction (LVEF) measured by MRI. Normal range of LVEF ranges from 50% to 70%. Borderline LVEF ranges from 41% to 49% Reduced LVEF ranges < 41% | Posted | Mean | Standard Deviation | percentage of ejection fraction | Baseline, 6 months |
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| Secondary | Six Minutes Walking Test | Quality of life will be assessed using Six minutes walking test, to see the changes of six minutes walking test before and after intervention Distances reported for healthy individuals ages 40 yo 85 years range from 400 to 700 m.. | Posted | Median | Inter-Quartile Range | meters | Baseline, 6 months |
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| Secondary | Wall Motion Score Index | Cardiac wall motion abnormality will be measured using Wall Motion Score Index with MRI. Each myocardial segment is assigned a score from 1 to 4. The 16 segment model of myocardial segmentation is recommended. A WMSI of 1.0 is considered normokinetic. A WMSI of 1.5 is considered mild hypokinesia A WMSI of 2.0 is considered hypokinesia A WMSI of 2.5 is considered severe hypokinesia A WMSI of 3.0 is considered akinetic. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 6 months |
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| Secondary | Myocardial Scar Size | Percentage of myocardial scar size proportion measured by MRI to quantify and define the extent/transmurality of scar tissue, the following definitions were used
| Posted | Mean | Standard Deviation | Percentage of Scar Area | Baseline, 6 months |
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| Secondary | Vascular Endothelial Growth Factor | Cytokine that has important role for angiogenesis. Normal range for plasma VEGF is 0-115 pg/ml | Posted | Mean | Standard Deviation | pg/ml | Baseline, 6 months |
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| Secondary | Left Ventricle End Systolic Volume | Left ventricle end-systolic volume is the volume of blood in a left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. Normal LVESV ranges is 37 - 57 mililiters. | Posted | Mean | Standard Deviation | milliliters | Baseline, 6 months |
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| Secondary | Minnesota Living With Heart Failure Questionnaire | Quality of life assessed using Minnesota Living With Heart Failure Questionnaire consist of 21 questions, to see the changes before and after intervention. Minimum score = 0, Maximum score = 105 Higher values represent a worse outcome | Posted | Median | Inter-Quartile Range | score on a scale | Baseline, 6 months |
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| Secondary | Left Ventricle End Diastolic Volume | Left ventricle end-diastolic volume is the volume of blood in the left ventricle at end load or filling in (diastole) or the amount of blood in the ventricle just before systole. Normal ranges of LVEDV is 121 - 163 mililiters | Posted | Mean | Standard Deviation | milliliters | Baseline, 6 months |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Subject | this arm will receive CABG + Transepicardial with Transseptal CD 133+ Implantation | 2 | 13 | 2 | 13 | 0 | 13 |
| EG001 | Control | this arm will receive CABG only | 1 | 13 | 1 | 13 | 0 | 13 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | Systematic Assessment |
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| Haemodynamic instability | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tri Wisesa Soetisna, M.D, MHA, PhD | National Cardiovascular Center Harapan Kita | +62215684093 | tricts2000@yahoo.com |
| Feb 25, 2020 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 25, 2020 | Feb 25, 2020 | ICF_001.pdf |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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