Transepicardial With Transseptal Autologous CD 133+ Bone Marrow Cell Implantation in Patient Following CABG Surgery

The Effect of Transepicardial Augmentation on Transseptal Autologous CD 133+ Bone Marrow Cell Implantation to Myocardial Perfusion in Patient Following Coronary Artery Bypass Grafting

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02870933

Enrollment

Registered

2016-08-17

Start date

2016-01-31

Completion date

2019-04-30

Last updated

2020-04-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease

Keywords

CD 133+, Transepicardial with Transseptal Implantation, CABG

Brief summary

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.

Detailed description

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.

Interventions

BIOLOGICALTransepicardial with Transseptal CD 133+ Implantation

Transepicardial with Transseptal CD 133+ Implantation

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to 70 Years

Healthy volunteers

Inclusion criteria

* patients with coronary artery disease 3 vessels disease indicated for CABG * LVEF \< 35% which has been confirmed by MRI * Patients with akinetic or hypokineic segment, and left ventricle myocardial hypoperfusion confirmed in MRI * has signed informed consent

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

Design outcomes

Primary

Measure	Time frame	Description
Myocardial Defect Perfusion	Baseline, 6 months	Number of heart wall segments with perfusion defect measured by MRI.
Left Ventricular Ejection Fraction	Baseline, 6 months	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%

Secondary

Measure	Time frame	Description
Myocardial Scar Size	Baseline, 6 months	Percentage of myocardial scar size proportion measured by MRI to quantify and define the extent/transmurality of scar tissue, the following definitions were used 1. spatial (circumferential) extent, the number of affected segments 2. nontransmurality, the number of segmments with a segmental scar score of 1 or 2, and transmurality, the number of segments with a segmental scar score of 3 or 4 3. total score, summed segmental scar scores per patient divided by 17 (which reflects the damage per patient)
Vascular Endothelial Growth Factor	Baseline, 6 months	Cytokine that has important role for angiogenesis. Normal range for plasma VEGF is 0-115 pg/ml
Six Minutes Walking Test	Baseline, 6 months	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..
Minnesota Living With Heart Failure Questionnaire	Baseline, 6 months	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
Left Ventricle End Diastolic Volume	Baseline, 6 months	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
Left Ventricle End Systolic Volume	Baseline, 6 months	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.
Wall Motion Score Index	Baseline, 6 months	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.

Countries

Indonesia

Participant flow

Participants by arm

Arm	Count
CABG + Transepicardial With Transseptal CD 133+ Implantation this arm will receive Transepicardial with Transseptal CD 133+ Implantation	13
Control this arm will not receive Transepicardial with Transseptal CD 133+ Implantation	13
Total	26

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	2	1
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Control	Total	CABG + Transepicardial With Transseptal CD 133+ Implantation
Age, Continuous	57.46 years STANDARD_DEVIATION 6.33	56.69 years STANDARD_DEVIATION 7.63	55.92 years STANDARD_DEVIATION 8.95
CCS grade III-IV	2 Participants	3 Participants	1 Participants
Diabetes	9 Participants	14 Participants	5 Participants
Diastolic blood pressure	72.46 mmHg STANDARD_DEVIATION 15.36	75.04 mmHg STANDARD_DEVIATION 13.52	78.00 mmHg STANDARD_DEVIATION 12.03
Dyslipidemia	11 Participants	17 Participants	6 Participants
Hypertension	7 Participants	16 Participants	9 Participants
Left Ventricle Ejection Fraction	30.18 Percentage of Ejection Fraction STANDARD_DEVIATION 3.85	28.03 Percentage of Ejection Fraction STANDARD_DEVIATION 5.23	25.88 Percentage of Ejection Fraction STANDARD_DEVIATION 5.66
Left Ventricle End-Diastolic Volume	200.89 mililiters STANDARD_DEVIATION 37.1	178.5 mililiters STANDARD_DEVIATION 47.58	156.10 mililiters STANDARD_DEVIATION 47.46
Left Ventricle End-Systolic Volume	141.05 mililiters STANDARD_DEVIATION 27.77	128.46 mililiters STANDARD_DEVIATION 33.99	115.87 mililiters STANDARD_DEVIATION 35.94
Menopause	1 Participants	2 Participants	1 Participants
Minnesotta Living with Heart Failure Score	21.46 units on a scale STANDARD_DEVIATION 8.76	25.88 units on a scale STANDARD_DEVIATION 12.16	30.3 units on a scale STANDARD_DEVIATION 13.73
Myocardial perfusion defect	15.38 Percentage of Myocardial Perfusion STANDARD_DEVIATION 4.87	15.57 Percentage of Myocardial Perfusion STANDARD_DEVIATION 4.62	15.76 Percentage of Myocardial Perfusion STANDARD_DEVIATION 4.38
Myocardial Scar Size	24.45 Percentage of Scar Area STANDARD_DEVIATION 13.73	26.11 Percentage of Scar Area STANDARD_DEVIATION 14.58	27.76 Percentage of Scar Area STANDARD_DEVIATION 15.76
NYHA grade III-IV	4 Participants	7 Participants	3 Participants
Race and Ethnicity Not Collected	—	0 Participants	—
Random blood sugar level	136.85 mg/dl STANDARD_DEVIATION 39	131.85 mg/dl STANDARD_DEVIATION 38.5	126.85 mg/dl STANDARD_DEVIATION 38.89
Region of Enrollment Indonesia	13 participants	26 participants	13 participants
Sex: Female, Male Female	1 Participants	2 Participants	1 Participants
Sex: Female, Male Male	12 Participants	24 Participants	12 Participants
Six minutes walk test	308.92 meters STANDARD_DEVIATION 79.37	303.0 meters STANDARD_DEVIATION 74.75	297.08 meters STANDARD_DEVIATION 72.56
Smoking	9 Participants	20 Participants	11 Participants
Systolic blood pressure	126.5 mmHg STANDARD_DEVIATION 19.6	123.38 mmHg STANDARD_DEVIATION 17.51	121.92 mmHg STANDARD_DEVIATION 14.37
Vascular Endothelial Growth Factor	40.46 pg/mL STANDARD_DEVIATION 40.08	43.66 pg/mL STANDARD_DEVIATION 101.75	46.86 pg/mL STANDARD_DEVIATION 141.2
Wall motion score index	2.07 units on a scale STANDARD_DEVIATION 0.31	2.2 units on a scale STANDARD_DEVIATION 0.28	2.32 units on a scale STANDARD_DEVIATION 0.17

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 13	1 / 13
other Total, other adverse events	0 / 13	0 / 13
serious Total, serious adverse events	2 / 13	1 / 13

Outcome results

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%