Heart Failure
Conditions
Brief summary
Heart failure has a high morbidity and mortality because the heart is one of the least regenerative organs in the human body. Drug treatments for heart failure manage symptoms but do not restore lost myocytes. Cellular replacement therapy is a potential approach to repair damaged myocardial tissue, restore cardiac function, which has become a new strategy for the treatment of heart failure. The purpose of this study is to assess the safety, feasibility and efficacy of intramyocardial delivery of cardiomyocytes at the time of coronary artery bypass grafting in patients with chronic heart failure.
Detailed description
Patients with heart failure will be treated with allogenic human pluripotent stem cell-derived cardiomyocytes ( hPSC-CM ) from healthy donors. The cells will be injected directly into the myocardium at time of coronary artery bypass grafting. Patients will be assessed at 1, 6 and 12 months after cell transplantation for safety, feasibility and efficacy.
Interventions
BIOLOGICALhPSC-CM Therapy
Injection of allogenic human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) during coronary artery bypass grafting surgery. 200 million hPSC-CMs in 2.5-5 mL medium suspension will be injected into the myocardium.
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Help Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
To ensure the study results are evaluated without bias, outcomes assessors will not be informed the randomization details.
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 35-75 (including 35 and 75). 2. Have signed the Informed Consent Form (ICF). 3. Patients have chronic left ventricular dysfunction. 4. Patients have NYHA Class III-IV cardiac function even after improved medication for the treatment of advanced chronic heart failure. 5. Patients have indications for Coronary Artery Bypass Grafting. 6. 20% ≤ LVEF ≤ 45% as determined by echocardiogram (data collected up to 6 months prior to inclusion evaluation are valid; data collected within 1 month since a myocardial infarction are invalid). 7. Weakening or absence of segmental regional wall motion as determined by standard imaging.
Exclusion criteria
1. PRA ≥ 20% or DSA-positive. 2. Patient received ICD transplantation, CRT or similar treatment. 3. Patients with valvular heart disease or received heart valvular disease 4. Patients received treatment of percutaneous transluminal coronary intervention (PCI) 5. Patients with atrial fibrillation 6. Patients previously suffered sustained ventricular tachycardia or sudden cardiac death. 7. Baseline glomerular filtration rate \<30ml/min/1.73m2. 8. Liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN. 9. Hematological abnormality: A hematocrit \<25% as determined by HCT, white blood cell\<2500/ul or platelet values \<100000/ul without another explanation. 10. Known, serious radiographic contrast allergy, penicillin allergy, streptomycin allergy. 11. Coagulopathy (INR\>1.3) not due to a reversible cause. 12. Contra-indication to performance of a MRI scan. 13. Recipients of organ transplant. 14. Clinical history of malignancy within 5 years (patients with prior malignancy must be disease free for 5 years). 15. Non-cardiac condition that limits lifespan \<1 year. 16. On chronic therapy with immunosuppressant medication, such as glucocorticoid and TNFα antagonist. 17. Patients allergy to or cannot use immunosuppressant. 18. Serum positive for HIV, HBV, HCV, TP. 19. Currently enrolled other investigational therapeutic or device study. 20. Patients who are pregnant or breast feeding. 21. Other conditions that researchers consider not suitable to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of sustained ventricular arrhythmias | 1~6 Month Post-operation | defined as the proportion of patients experiencing ventricular arrhythmias lasting more than 30 seconds |
| Incidence of newly formed tumors | 1~12 Month Post-operation | by comparing chest, abdominal and pelvic CT scan and PET-CT scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Left Ventricular systolic performance as assessed by PET/ECT Scan | Baseline, 6 and 12 Months Post-operation | Myocardium perfusion |
| Functional status by 6 minute walk test | Baseline, 6 and 12 Months Post-operation | Evaluate Functional Capacity via the Six Minute Walk Test |
| Functional status by New York Heart Association (NYHA) Classification | Baseline, 6 and 12 Months Post-operation | Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination |
| Minnesota Living With Heart Failure Questionnaire (MLHFQ) | Baseline, 1, 6 and 12 Months Post-operation | Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF). The Maximum possible scores being 105 and the minimum 0. Higher scores indicate a worse or worsening quality of life, while lower scores or decreasing scores indicate a better quality of life. |
| Incidence of Major Adverse Cardiac Events (MACE) | Baseline, 1~12 Months Post-operation | Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) non-lethal myocardial infraction, and (3) hospitalization for worsening HF |
| Overall Left Ventricular systolic performance as assessed by MRI | Baseline, 6 and 12 Months Post-operation | Size of infracted myocardium, left ventricular side wall thickness at diastolic, interventricular septum thickness, left ventricular ejection fraction, left ventricular end-systolic volume and end-diastolic volume, stroke volume, cardiac output, myocardium density and left ventricular mass at diastolic will be evaluated and compared to baseline values. |
| Changes in penal reactive antibodies (PRA) | Baseline, 1, 6 and 12 Months Post-operation | Changes in penal reactive antibodies (PRA) as assessed via blooddraw |
| Changes in donor specific antibodies (DSA) | Baseline, 1, 6 and 12 Months Post-operation | Changes in donor specific antibodies (DSA) as assessed via blooddraw |
| Incidence of severe arrhythmia | First month post-operatively | Clinically significant arrhythmias will be recorded by Electrocardiogram monitoring |
| Changes in cytokines | Baseline,1, 6 and 12 Months Post-operation | Change in NT-proBNP as assessed via blooddraw |
| Incidence of Serious Adverse Events (SAE) | Baseline, 1~12 Months Post-operation | SAE justified (all undesirable or unintended diseases or laboratory and imaging disorders and symptoms that occur in subjects after CABG surgery and 12 months postoperative follow-up, or until the subject withdrawals from the study. AE grading will be based on Common Terminology Criteria for Adverse Events (CTCAE) V5.0.) |
| Overall Left Ventricular systolic performance as assessed by Echocardiogram | Baseline, 6 and 12 Months Post-operation | Interventricular septum thickness at diastolic, left ventricular end-systolic diameter and end-diastolic diameter, left ventricular posterior wall thickness at diastolic, left atrial diameter, left ventricular ejection fraction, mitral flow pattern (E/A) will be evaluated and compared to baseline values. |
Countries
China
Outcome results
None listed