Heart Failure
Conditions
Brief summary
The purpose of this clinical study is to evaluate the feasibility, safety and efficacy of intramyocardial injection of human induce pluripotent stem cell-derived cardiomyocytes (HiCM-188) during coronary artery bypass grafting (CABG) surgery in patients with severe chronic ischemic heart failure.
Detailed description
This is a single center, open-label, three-group dose-escalation (phase I) study followed by dose-extension (phase IIa) study in up to 36 severe ischemic heart failure patients. It is estimated that up to 18 phase I patients will be received HiCM-188 intramyocardial injection during CABG surgery. The maximum number of subjects after dose escalation and dose extension studies in each dose group is 12. All the subjects need take immunosuppressant after transplantation.
Interventions
DRUGHiCM-188 therapy
Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes (HiCM-188) during coronary artery bypass grafting surgery
Sponsors
Help Therapeutics
TEDA International Cardiovascular Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Willingness and ability to give written informed consent 3. Nuclide-myocardial metabolic perfusion imaging or Magnetic Resonance Imaging (MRI) revealed infarcted myocardium in the left anterior descending branch (LAD) coronary artery supply area 4. LVEF\<50% as assessed by Echocardiography or LVEF≤40% as assessed by MRI 5. Patients have indications for Coronary Artery Bypass Grafting
Exclusion criteria
1. Presence of a pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy device (CRT) 2. Diagnosed with malignancy within 5 years 3. Autoimmune disease 4. Recipients of organ transplant. 5. Patients undergoing other surgical operations (excluding resection of ventricular aneurysm and left atrial appendage excision/occlusion). 6. Severe ventricular arrhythmia 7. Contraindication to CABG surgery 8. Contraindication to cardiac MRI or PET/CT scan. 9. Contraindication to immunosuppressants 10. Participation in another clinical trial within 3 months prior to screening 11. Pregnancy, lactation, or a positive serum pregnancy test 12. Any other condition considered by the investigator to be inappropriate for inclusion in this clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of major Serious Adverse Events (SAE) | Within the first month after surgery | The incidence of major Serious Adverse Events (SAE) within the first month after surgery, including pericardial tamponade, nonfatal myocardial infarction, stroke, and all-cause death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade 4 or above arrhythmias Related to HiCM-188 Cell Therapy | Within the first month after surgery | Grade 4 or above arrhythmias associated with the HiCM-188 therapy within the first month after surgery |
| The incidence of tumor | 12 months after surgery | assessed by PET whole-body imaging at baseline and 12 months after HiCM-188 therapy |
| Left ventricular geometry as assessed by cardiac magnetic resonance imaging (MRI) | Baseline, 6 and 12 months after surgery | Left ventricular wall thickness, interventricular septum thickness |
| Size of myocardial infarction as assessed by MRI | Baseline, 6 and 12 months after surgery | Size of myocardial infarction |
| Ventricular wall motion as assessed by MRI | Baseline, 6 and 12 months after surgery | Ventricular wall motion |
| Left ventricular ejection fraction as assessed by MRI | Baseline, 6 and 12 months after surgery | Left ventricular ejection fraction |
| Cardiac Volumes as assessed by MRI | Baseline, 6 and 12 months after surgery | Left ventricular end-diastolic volume (LVEDV), Left ventricular end-systolic volume (LVESV) and Stroke Volume (SV) |
| Cardiac output (CO) as assessed by MRI | Baseline, 6 and 12 months after surgery | Cardiac output (CO) |
| End-diastolic myocardial mass as assessed by MRI | Baseline, 6 and 12 months after surgery | End-diastolic myocardial mass |
| Left ventricular ejection fraction (LVEF) as assessed by Echocardiography | Baseline, 6 and 12 months after surgery | Left ventricular ejection fraction |
| Fractional shortening (FS) as assessed by Echocardiography | Baseline, 6 and 12 months after surgery | Fractional shortening |
| Left ventricular dimensions as assessed by Echocardiography | Baseline, 6 and 12 months after surgery | Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter(LVESD)and left atrial diameter |
| Cardiac Volumes as assessed by Echocardiography | Baseline, 6 and 12 months after surgery | Left ventricular end- diastolic volume (LVEDV) and Left ventricular end-systolic volume(LVESV) |
| Mitral valve inflow spectrum(E/A) as assessed by Echocardiography | Baseline, 6 and 12 months after surgery | Mitral valve inflow spectrum (E/A) |
| Longitudinal strain as assessed by Echocardiography | Baseline, 6 and 12 months after surgery | Longitudinal strain |
| Myocardial viability as assessed by SPECT | Baseline, 6 and 12 months after surgery | Myocardial viability |
| Myocardial blood flow as assessed by SPECT | Baseline, 6 and 12 months after surgery | Myocardial blood flow |
| NT-proBNP Levels | Baseline, 6 and 12 months after surgery | The changes of NT-proBNP Levels |
| 6-minute walking distance | Baseline, 6 and 12 months after surgery | The changes of 6-minute walking distance at 6M and 12M after HiCM-188 therapy |
| New York Heart Association (NYHA) functional classification | Baseline, 6 and 12 months after surgery | The changes of New York Heart Association (NYHA) functional classification at 6M and 12M after HiCM-188 therapy |
| Changes of Quality of Life (QoL) as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ) | Baseline, 6 and 12 months after surgery | The MLHFQ is a self-administered disease-specific outcome measure instrument for patients with heart failure (HF), comprising 21 items rated on Likert scales, representing different degrees of impact of HF on QoL. The MLHFQ scores are on a range of 0-105, in which higher scores reflect better health status. |
| Changes of Quality of Life(QOL) as assessed by 36-Item Short Form Survey (SF-36) | Baseline, 6 and 12 months after surgery | The 36-Item Short Form Survey(SF-36) is a self-administered outcome measure instrument that comprises 36 items grouped into 8 dimensions: limitations in physical activities because of health problems, limitations in social activities because of physical or emotional problems, limitations in usual role activities because of physical health problems, bodily pain, general mental health, limitations in usual role activities because of emotional problems, vitality, general health perceptions. The SF-36 scores are on a range of 0-100, in which higher scores reflect better health status. |
Countries
China
Outcome results
None listed