Clinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic
试验速览
- 阶段
- 1 期
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- The number of patients with improved LVEF
研究概览
简要总结
Targeting patients with severe ischemic cardiomyopathy, the purpose of this study is as follows: to confirm short-term efficacy by observing changes and transitions in cardiac function and clinical symptoms compared with each patient's baseline (before and after comparison) by human iPS cell-derived cardiomyocyte sheet transplantation, and to evaluate the safety and tolerability including the combined use of immunosuppressants.
详细描述
The objective of this study is to confirm the efficacy and safety of a human (allogeneic) iPS cell-derived cardiomyocyte sheet in combination with an immunosuppressant for ischemic cardiomyopathy patients. The primary evaluation items will be improvement of left ventricular systolic function (LVEF) for efficacy, and safety will be assessed by blood tests, general laboratory tests, and other safety-related evaluations. Secondary evaluation items are NYHA functional evaluation, left ventricular remodeling evaluation by echocardiography, hemodynamic evaluation, physical activity function evaluation such as 6MWD and SAS, QOL, and exercise tolerance evaluation by questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with chronic ischemic heart disease
- •Patients with Grade III-IV NYHA Functional Classification heart failure
- •Patients who are in the state of heart failure despite maximal oral medications including digitalis, diuretics, ACE inhibitors, ARBs, beta-blockers, anti-aldosterone drugs, and oral cardiotonics
- •Patients who are 20 years of age or older at the point of consent
- •Patients at risk of worsening heart failure despite being under standard surgical treatment (coronary artery bypass surgery, mitral valve angioplasty, left ventricular angioplasty, cardiac resynchronization therapy, and percutaneous coronary intervention) for more than 3 months
- •Patients with LVEF (Echocardiography) at rest of 35% or less
- •Patients whose informed consent for clinical trial participation can be obtained from the subject himself/herself in writing
- •Patients who can continue to visit to the clinical trial site for 52 weeks after obtaining consent, continue to live in Japan, and can be expected to have data collected by NRMD/PMS
排除标准
- •Patients with autoimmune diseases
- •Patients with allergies or hypersensitivity to the immunosuppressant used
- •Patients with active infections
- •Patients who remain in shock due to worsening heart failure
- •Patients with irreversible organ failure other than heart
- •Patients with malignant tumors
- •Patients who are or may be pregnant
- •Patients with history of alcoholism or drug addiction within six months from the day of consent
- •Patients with allergies or hypersensitivity to animals such as cattle from which the raw materials are derived
- •Patients with severe pulmonary hypertension
- •Patients within 6 months of completion of other clinical trials at the time of enrollment
- •In addition, patients with other cardiovascular abnormalities who are determined to be unfit for this study as per the judgment of the patient enrollment study committee of physicians
结局指标
主要结局
The number of patients with improved LVEF
时间窗: 26 weeks
The number of patients with improved LVEF by echocardiography 26 weeks postoperatively compared with preoperatively.
Incidence of abnormal vital signs [Safety and Tolerability]
时间窗: Before surgery, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Regarding changes in vital signs(Body temperature, blood pressure (systolic, diastolic), and pulse rate), summary statistics and changes at each measurement time point will be obtained.
Incidence of abnormal blood biochemical tests [Safety and Tolerability]
时间窗: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Regarding changes in blood biochemistry tests(AST(GOT), ALT(GPT), LDH, ALP, BUN, Cre, UA, TG, T-Cho, LDL-Cho, Alb, CK, CK-MB, electrolytes (Na, K, Cl, Ca, iP, Mg), CRP, blood sugar), summary statistics and changes at each measurement time point will be obtained.
Incidence of abnormal tumor marker tests [Safety and Tolerability]
时间窗: Screening, 13 weeks, 26 weeks, 52 weeks
Regarding changes in tumor marker tests(AFP, CA19-9, CEA, hCG), summary statistics and changes at each measurement time point will be obtained.
Incidence of cardiac function clinical events such as death and hospitalization [Safety and Tolerability]
时间窗: From postoperative to the end of the observation period (52 weeks)
With respect to the incidence of cardiac function clinical events such as death and hospitalization, the number of cases in which the causes of death are related to heart disease and those unrelated to heart disease will be determined for cases of death.
Incidence of adverse events and defects [Safety and Tolerability]
时间窗: From postoperative to the end of the observation period (52 weeks)
Regarding adverse events and side effects (of the adverse events, those whose causal relationship with the clinical trial product is determined to be other than "not related" will be treated as side effects.) the number of occurrences and the number of occurrence examples by event and severity will be obtained.
Incidence of serious adverse events [Safety and Tolerability]
时间窗: From postoperative to the end of the observation period (52 weeks)
Regarding serious adverse events, the number of occurrences and the number of occurrence examples by event and severity will be obtained.
Incidence of abnormal general blood tests [Safety and Tolerability]
时间窗: Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks
Regarding changes in general blood tests(WBC, RBC, Hb, Ht, PLT), summary statistics and changes at each measurement time point will be obtained.
次要结局
- Number of Responder patients 26 and 52 weeks after transplantation of this product(26 and 52 weeks)
- Contraction function of the entire left ventricle(26 weeks)
- Left ventricular remodeling (LVESVI)(26 weeks)
- Left ventricular remodeling (LVEDVI)(26 weeks)
- New York Heart Association functional classification(Before surgery, 26 weeks, 52 weeks)
- Specific Activity Scale (SAS)(Before surgery, 26 weeks, 52 weeks)
- 6-minute walking distance(Before surgery, 26 weeks, 52 weeks)
- Brain natriuretic peptide (BNP)(Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks)
- The Minnesota Living with Heart Failure Questionnaire(Before surgery, 26 weeks, 52 weeks)
- 36-Item Short Form Survey (SF-36)(Before surgery, 26 weeks, 52 weeks)
- N-terminal pro-brain natriuretic peptide (NT-proBNP)(Before surgery, 1 days, 7 days, 14 days, 4 weeks, 13 weeks, 26 weeks, 52 weeks)
- Exercise tolerance (VO2max)(Before surgery, 26 weeks, 52 weeks)
- Exercise tolerance (AT)(Before surgery, 26 weeks, 52 weeks)
- Exercise tolerance (VE/VCO2)(Before surgery, 26 weeks, 52 weeks)
- Cumulative number of rejections that occurred during the observation period(26 weeks)
研究者
Koichi Toda
Associate Professor
Osaka University