Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 53
- 试验地点
- 3
- 主要终点
- Adverse events
研究概览
简要总结
The BioVAT-HF trial will test the hypothesis that cardiomyocyte implantation via engineered heart muscle (EHM), the proposed investigational medicinal product (IMP; designated "Biological Ventricular Assist Tissue" or BioVAT), results in sustainable remuscularization and biological enhancement of myocardial performance in the failing heart. EHM are constructed from defined mixtures of induced pluripotent stem cell (iPSC)-derived cardiomyocytes and stromal cells in a bovine collagen type I hydrogel. Comprehensive preclinical testing confirmed the rationale for the clinical translation of the myocardial remuscularization strategy by EHM implantation. The patient target population for EHM therapy is patients suffering from advanced heart failure with reduced ejection fraction (HFrEF; EF: ≤35%) and no realistic option for heart transplantation.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic heart failure (NYHA II-IV) with reduced ejection fraction (HFrEF with LVEF ≤35%) as assessed by echocardiography.
- •Patients on guideline-directed medical therapy
- •NT-proBNP >300 pg/mL for patients in sinus rhythm or >900 pg/mL if in atrial fibrillation
- •History of previous heart failure hospitalization in the past 12 months
- •At least one hypo- or dyskinetic segment or dilated heart chamber to demark the implant target area
- •(A) Stable disease condition allowing for an elective left-lateral mini-thoracotomy (for LV applications) or (B) open-chest surgery (for RV applications) for a clinically indicated intervention on the LV (e.g., coronary bypass surgery, valve repair, mechanical circulatory support device implantation) with concomitant RV dysfunction, diagnosed using the Tricuspid Annular Plane Systolic Excursion (TAPSE) index <16 mm (Rudski et al. 2010).
- •18-80 years of age
- •Willingness and ability to give written informed consent
- •Female subjects of childbearing potential must agree to use acceptable method(s) of contraception for the full study duration.
排除标准
- •Contraindication to immunosuppressive drugs (e.g. known history of unresolved cancer, hepatitis B/C, HIV, HTLV1)
- •Contraindication to TachoSil® (e.g. hypersensitivity to human fibrinogen, human thrombin, horse collagen, human albumin, Riboflavin, Natriumchloride, Natriumcitrate, L-Arginin-Hydrochloride)
- •Hypertrophic cardiomyopathy (HCM)
- •Terminal kidney failure (stage 4; GFR <30 ml/min) at the time of enrolment
- •Terminal liver failure (Child-Pugh stage C; score >10) at the time of enrolment
- •History of disabling stroke
- •Reduced life expectancy in the short term due to non-cardiac disease
- •Any condition that excludes adherence to study protocol (in particular lack of adherence to prescribed medication)
- •Simultaneous participation in another interventional trial
- •Pregnant or breastfeeding females
- •Known or suspected alcohol and/or drug abuse
研究组 & 干预措施
EHM Implantation
All patients will receive EHM implant
干预措施: EHM implantation (Biological)
结局指标
主要结局
Adverse events
时间窗: 12 months
Number of Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (Part A) and the whole study duration (Part B)
Heart target heart wall thickness
时间窗: 12 months
Change of target heart wall thickness (TWTh in mm) Echo or cCT or cMRI
LV/RV-ejection fraction
时间窗: 12 months
Change of LV/RV-ejection fraction (LV/RV-EF in %) Echo or cCT or cMRI
Patient reported outcome
时间窗: 12 months
Patient reported outcome Change of KCCQ-23 OSS (Overall Summary Score)
次要结局
- Major adverse cardiac events(12 months)
- Arrhythmic events(12 months)
- Immune rejection(12 months)
- Mechanical perturbation of ventricular function(12 months)
- Recurrent hospitalizations for heart failure(12 months)
- Mechanical circulatory assist device implantation(12 months)
- Heart transplantation(12 months)
- Cardiopulmonary stress testing (VO2max)(12 months)
- Cardiopulmonary stress testing six-minute walk test (6MWT)(12 months)
- Hand-grip strength(12 months)
- NYHA classification(12 months)
- Quality of life score (EQ-5D-5L)(12 months)
- Hospital Anxiety and Depression Scale (HADS)(12 months)
- Mortality(12 months)
- Montreal Cognitive Assessment (MoCA)(12 months)
- Medication adherence(12 months)
- Brief Illness Perception Questionnaire (B-IPQ)(12 months)
- Treatment Expectation Questionnaire (TEX-Q)(12 months)
研究者
Karsten Gavenis
on behalf of Principal Investigator Prof. Seidler and Study Director Prof. Zimmermann
University Medical Center Goettingen