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
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Part A (Dose Escalation steps): Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (based on a comparison of data obtained during visit 2 and visit 7)
研究概览
简要总结
Primary objectiv is to assess safety and efficacy of Engineered Human Myocardium (EHM) in patients with terminal heart failure (HFrEF EF ≤35%) with or without RV dysfunction (TAPSE <16 mm)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non-randomized
- 主要目的
- Trial phase
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Heart failure with reduced ejection fraction (HFrEF with EF ≤ 35%) as assessed by high-resolution echocardiography and MRI or CT.
- •At least one hypo- or dyskinetic segment to demark the implant target area.
- •Stable disease condition allowing for an elective left-lateral mini-thoracotomy (for LV applications) or 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
- •Previous implantation of an ICD or CRT-D with event recorder
- •New York Heart Association (NYHA) Class III or IV under optimal medical therapy
- •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)
- •Simultaneous participation in another interventional trial
- •Pregnant or breastfeeding females
- •Known or suspected alcohol and/or drug abuse
- •Contraindication to TachoSil® (e.g. hypersenstitivity 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
- •Autoimmune disease
- •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)
结局指标
主要结局
Part A (Dose Escalation steps): Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (based on a comparison of data obtained during visit 2 and visit 7)
Part A (Dose Escalation steps): Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within 28 days (based on a comparison of data obtained during visit 2 and visit 7)
Part B: Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within the whole study duration
Part B: Adverse events related to the procedure, including in particular arrhythmic events and worsening of disease progression within the whole study duration
Evidence for structural and functional muscular augmentation of target myocardium determined as enhanced target heart wall thickness (HWT) and thickening fraction (HWTF)
Evidence for structural and functional muscular augmentation of target myocardium determined as enhanced target heart wall thickness (HWT) and thickening fraction (HWTF)
次要结局
- All-cause and cardiovascular mortality
- Frequency of major adverse cardiac events (MACE; non-fatal myocardial infarction, non-fatal stroke and cardiovascular death)
- Frequency and severity of arrhythmic events
- Incidence of immune rejection (allograft DNA, CK/CK-MB, cTnT. DSA)
- Incidence of mechanical perturbation of ventricular function by EHM graft
- Recurrent HF hospitalizations
- Left ventricular ejection fraction (EF)
- Change in heart failure medication
- Functional status in patients as determined by cardiopulmonary stress testing (VO2max), six-minute walk test (6MWT), and hand-grip strength measurements
- Patient reported outcomes assessed by NYHA classification, quality of life score (KCCQ, EQ-5D, QoL-VAD), and study adherence motivation (PHQ-9, HAF-17, ESSI, LOT-R, ULS-8, medication adherence, Trust/Mistrust in medical staff)
研究者
Florian Walker
Scientific
Universitaetsmedizin Goettingen