A First-in-Human Feasibility Study to Evaluate the Safety (and Short Term Effectiveness) of the Autologous GrOwnValve Transcatheter Pulmonary Heart Valve [GECT]
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Position and condition of the stent and structures
研究概览
简要总结
Aim of this study is to investigate the clinical safety of a novel pediatric heart valve.
详细描述
Defective or diseased pulmonary heart valves do not recover. If left untreated, pediatric and adult patients alike, face serious risks of progressive heart failure and death. Due to the insufficient care of children with heart valve defects, the valve replacement with regenerative, remodeling, and growth potential remains an unmet medical need. Therefore, the first pediatric heart valve (GrOwnValve) was developed to overcome the current limitations, which should offer regenerative potential that adapts to the somatic growth of the child. The study aims to investigate the safety and provide the first initial efficacy estimates of the transcatheter implantable GrOwnValve. This first prospective, non-randomized, single center trial in 7 study subjects (≥ 18 years of age) should be conducted to assess the devices safety for clinical application.
The novel interdisciplinary solution approach is based on the combination of individualized 3D modeling, viable autologous tissue (contrary to all other prosthetic heart valves on the market), and preservation of the regenerative capacity of the valve replacement by maintaining the vitality of heart valve cells and tissue through the application of a novel crosslinker in the tissue preparation process. The GrOwnValve prothesis has the potential to be the first durable and regenerative heart valve for adults. Fabrication is performed on-demand in the operating room. The trial should be the first clinical investigation assessing this novel heart valve replacement approach. We are aiming for the GrOwnValve to be the standard of care, replacing current solutions.
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
- •Age ≥ 18 years
- •Sufficient appropriate tissue (preferably: Pericardium for pericardiectomy via thoracoscopy or thoracotomy, or sternotomy; other options are fascia lata, rectus fascia, peritoneum or diaphragm)
- •Any of the following by transthoracic echocardiography and/or Cardiac Magnet Resonance Imaging:
- •For patients in New York Heart Association (NYHA) Classification II, III, or IV: Moderate (3+) or severe (4+) pulmonary regurgitation AND/OR mean systolic gradient across PV or RVOT ≥ 35 mmHg
- •For patients in NYHA Classification I: Severe (4+) pulmonary regurgitation with RV dilatation or dysfunction and/or mean PV or RVOT systolic gradient ≥ 40 mmHg
- •Right ventricular ejection fraction (RV-EF): <40%.
- •Right ventricular end-diastolic volume (RVEDV): >150 ml/m2 (body surface area)
- •Written informed consent provided by study subjects obtained before any research-related test is performed
排除标准
- •Active endocarditis or myocarditis or within 3 months before the screening date
- •Patients unwilling or unable to provide written informed consent or comply with follow-up requirements
- •Obstruction of the central veins (including the superior and inferior vena cava, and bilateral iliac veins) such that the Ensemble-delivery system/ Performer™ - Guiding Sheath/ Extra Large Check-Flo® or GORE® DrySeal Flex + Ballon-in-Ballon-catheter cannot be advanced to the heart via a transvenous approach from either femoral vein or internal jugular
- •Requires emergency surgery
- •Recipient of transplanted organs or currently an organ transplant candidate
- •Pulmonary hypertension
- •Connective tissue disorders
- •Coronary artery disease
- •Immunosuppressive disease
- •Estimated survival of less than 6 months
- •Fertile females unable to take adequate contraceptive precautions (PEARL- Index < 1%)
- •Females who are pregnant, or are currently breastfeeding an infant
- •Acute myocardial infarction within 30 days of the screening date
- •Stroke confirmed by CT, cerebrovascular accident (CVA), or transient ischemic attack (TIA) within 6 months before the screening date
- •Hemodynamic or respiratory instability requiring inotropic or/and mechanical circulatory support, or mechanical ventilation within 30 days before the screening date
- •Severe left ventricular systolic dysfunction with ejection fraction ≤ 20% or evidence of an intra-cardiac mass, thrombus, or vegetation assessed by echocardiography before the screening date
- •Renal insufficiency with creatinine level 2.5 mg/dl within 60 days before the screening date
- •Leukopenia with WBC <3.5 x 109/L anemia with Hgb <10 g/dl, or thrombocytopenia with platelet count <50x103/l accompanied by a history of bleeding diathesis or coagulopathy within 60 days before the screening date
- •Adult subject is an illicit drug user, alcohol abuser, or unable to give informed consent
- •Subject is institutionalized by court order or by order of authority (e.g. prisoner, untreated psychiatry; limited compliance)
- •Major or progressive non-cardiac disease (liver failure, renal failure, cancer)that has a life expectancy of less than six months Inability to comply with all of the study procedures and follow-up visits
- •Subjects who are dependent on the sponsor or investigators
结局指标
主要结局
Position and condition of the stent and structures
时间窗: Up to 1 Year Follow-Up
Measurement tool: Echocardiography + Magnetic resonance imaging + computed tomography Parameter: 1.) GrOwnValve annulus, 2.) no broken struts of the valve stent Decision rule: 1.) +/- 1.5 mm from the native pulmonary valve annulus, 2.) n.a.
Death
时间窗: Up to 5 Years Follow-Up
(valve-related, sudden, cardiac, and all-cause death)
Heart rhythm
时间窗: Up to 5 Years Follow-Up
Assessment if new or higher grade of cardiac arrhythmia occured, i.e. newly ventricular extra systoly
Valve opening and closure behavior
时间窗: Up to 5 Years Follow-Up
Measurement tool: Echocardiography + Magnetic resonance imaging Parameter: 1.) blood flow velocity / stenosis, 2.) stiff leaflet, 3.) valve opening area Decision rule: blood flow velocity \>4 m/s, abnormal or no leaflet motion when compared to neighboring leaflets, \> 0.70 for 17 diameter, \> 0.85 for 19, \> 1.05 for 21, \> 1.25 for 23, \> 1.45 for 25, \> 1.70 for 27, 1.95 for 29, and 2.25 for 31 mm annulus diameter
Valve closure behavior
时间窗: Up to 5 Years Follow-Up
Measurement tool: Echocardiography + Magnetic resonance imaging Parameter: 1.) vena contracta, 2.) Proximal Isovelocity Surface Area (PISA) radius, 3.) Effective regurgitation orifice area (EROA=2π\*r2\*Va/Vmax), (iv) sagging leaflet Decision rule: 1.) less than or equal to 15% of the diameter of PA/stent at a Nyquist limit of 0.5-0.6 m/s, frame rate \>20/sec, gain adjusted, sector small, 2.) equal or minor to 4 mm at a Nyquist limit of 0.2-0.4 m/s, frame rate \>20/sec, gain adjusted, variance off, sector small, 3.) \< or equal to 3% of the total cross-sectional area of the valve, 4.) n.a
Major bleeding
时间窗: Up to 1 Year Follow-Up
Assessment if device-related major bleeding has occured by laboratory + echo + CT
Oxygen supply
时间窗: Up to 5 Years Follow-Up
Measurement tool: Spiroergometry Parameters: cardiac rhythm, load duration, reason for termination, Heart rate at rest, blood pressure, maximum load level, VE/VCO2, PetCO2, VE/VCO2 slope, VO2, Respiratory rate, VD/VT, SpO2, RER, Borg score, FEV1, FVC
Reoperation
时间窗: Up to 5 Years Follow-Up
Questioning if device-related re-operation occured
Acute device-related complications
时间窗: Up to 5 Years Follow-Up
Measurement tool: Spiroergometry o Parameters: cardiac rhythm, load duration, reason for termination, Heart rate at rest, blood pressure, maximum load level, VE/VCO2, PetCO2, VE/VCO2 slope, VO2, Respiratory rate, VD/VT, SpO2, RER, Borg score, FEV1, FVC
Blood flow
时间窗: Up to 1 Year Follow-Up
Assessment of backflow and volume of blood by echo + MRI
次要结局
- Availability of pericardium or other tissue for preparation of autologous pulmonary valve graft(Procedure (intra-operatively))
- Post-procedure length of stay(Up to day of discharge ( ≤ 30 days))
- Ventilation time(Procedure (intra-operatively))
- Freedom from conduction disturbances and arrhythmias need for permanent pacemaker implantation(Up to 3 months Follow-Up)
- (Re-)Hospitalization(Up to 60 months (5 years) Follow-Up)
- Comparison of pericardiectomy (if applicable) via thoracoscopy vs. thoracotomy(Procedure (intra-operatively))
- Availability of pericardium or other tissue for preparation of autologous pulmonary valve graft(Procedure (intra-operatively))
- Post-procedure length of stay(Up to day of discharge ( ≤ 30 days))
- (Re-)Hospitalization(Up to 60 months (5 years) Follow-Up)
- Ventilation time(Procedure (intra-operatively))
- Freedom from conduction disturbances and arrhythmias need for permanent pacemaker implantation(Up to 3 months Follow-Up)
- Comparison of pericardiectomy (if applicable) via thoracoscopy vs. thoracotomy(Procedure (intra-operatively))
- Procedure-related death, major bleeding, reoperation, and other complications.(Follow-Up for 6 months)
研究者
Univ.-Prof. Dr. med. Frank Edelmann
Univ.-Prof. Dr. med.
Charite University, Berlin, Germany