Treating Congestive Heart Failure Patients With Human iPSC-derived Cardiomyocytes Through Catheter-based Endocardial Injection
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of major serious adverse events (SAEs)
研究概览
简要总结
Heart failure is the primary cause of morbidity and mortality worldwide. Currently drug treatments for heart failure manage the symptoms, but not restore the loss cardiomyocytes due to the very limited regenerative capability in the adult heart. Novel reparative therapies that replace the cardiomyocytes loss are highly demanded to restore the cardiac function. The main purposes of this explanatory study is to investigate the safety and efficacy of the catheter-based endocardial delivery of human iPSC-derived cardiomyocytes in patients with congestive heart failure.
详细描述
Patients with severe congestive heart failure will be treated with allogeneic human iPSC-derived cardiomyocytes (HiCM-188) through the catheter-based injections. HiCM188, produced by Help therapeutics with cGMP condition, will be transplanted into the myocardium through a transcatheter endocardial injection system with two dosage (100 million cells or 400 million cells). The safety and efficacy assessments will be conducted at1, 3, 6 and 12 months after the cell transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-75 years (including 18 and 75).
- •Signed the informed consent.
- •Patients with congestive heart failure who have received regular treatment for heart failure.
- •New York Heart Association (NYHA) Class III or IV despite optimal standard of care
- •Left Ventricular Ejection Fraction (LVEF)<40% as assessed by echocardiography ( measure in the 3 months of recruit is included, excluding the measured values within 1 month of myocardial infarction ）
- •The thickness of left ventricular ≥8mm
- •Female patient who is not pregnant or nursing during the clinical trial
排除标准
- •PRA ≥ 20% or DSA positive.
- •Patients received treatments such as pacemakers, ICD or CRT device.
- •Patient with severe valvular disease or presence of a mechanical valve replacement, such as PCI implantation, or patients requiring simultaneous radiofrequency ablation of atrial fibrillation.
- •Patient with any therapeutic traumatic heart surgery within 30 days.
- •Hemodynamic instability or cardiogenic shock.
- •Right heart failure.
- •Restrictive cardiomyopathy such as amyloidosis, sarcoidosis or hematochromia, constrictive pericarditis.
- •Myocardial infarction occurred within 30 days or stroke occurred within 60 days before enrollment.
- •Thickness at left ventricular free wall infarction < 6 mm.
- •Severe ventricular arrhythmias (persistent ventricular tachycardia or other conditions that the investigator considers necessary to exclude).
- •Baseline glomerular filtration rate < 30 ml/min / 1.73 m
- •Abnormal liver function: ALT or AST 3 times higher than the normal value.
- •Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cells count <2,500/ul or platelet count <100000 / ul.
- •Known allergies to penicillin, streptomycin or radiocontrast agent.
- •Abnormal coagulation function, INR > 1.3, which cannot be corrected.
- •Contra-indication to performance of a magnetic resonance imaging scan and PET/ECT examinations.
- •Organ transplant recipient
- •Patients with other malignant disease within 5 years prior to enrollment.
- •Non-cardiac condition that limits lifespan to < 1 year
- •On chronic therapy with immunosuppressant medication such as glucocorticoid or TNFα antagonist
- •Contra-indication to take immunosuppressant medication.
- •Serum positive for infectious diseases (HIV, HBV, HCV, TP).
- •Participated in other clinical trials within the previous 3 months .
- •Female patient who is pregnant or nursing.
- •Other condition that the investigator considers inappropriate for participation in the study.
结局指标
主要结局
Incidence of major serious adverse events (SAEs)
时间窗: First month post-catheterization
Incidence of SAEs is defined as the composite of: death, fatal myocardial infarction, stroke, tamponade, cardiac perforation, ventricular arrhythmias affecting hemodynamics (\> 15s), and tumorigenicity related to the hiPSC-CM .
次要结局
- Overall Left Ventricular systolic performance as assessed by MRI(Baseline, 1, 3, 6 and 12 months post-catheterization)
- Incidence of severe arrhythmia(1-6 months post-catheterization)
- Incidence of newly formed tumors(Baseline, 1,3,6 and 12 months post-catheterization)
- Changes in donor specific antibodies (DSA)(Baseline, 1, 3 and 6 months post-catheterization)
- Changes in penal reactive antibodies (PRA)(Baseline, 1, 3 and 6 months post-catheterization)
- Overall Left Ventricular systolic performance as assessed by PET/ECT Scan(Baseline, 6 and 12 months post-catheterization)
- Functional status by 6 minute walk test(Baseline, 1,3,6 and 12 months post-catheterization)
- Functional status by New York Heart Association (NYHA) Classification(Baseline, 1,3,6 and 12 months post-catheterization)
- Minnesota Living With Heart Failure Questionnaire (MLHFQ)(Baseline, 1,3,6 and 12 months post-catheterization)