Clinical Development and Proof of Principle Testing of New Regenerative Adenovirus Vascular Endothelial Growth Factor (VEGF-D) Therapy for Cost-effective Treatment of Refractory Angina. A Phase II Randomized, Double-blinded, Placebo-controlled Study (ReGenHeart)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- Severity of angina pectoris symptoms at 6 months
研究概览
简要总结
The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus-mediated vascular endothelial growth factor-D (AdVEGF-D) regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
详细描述
Study overview:
The purpose of the study is to evaluate the safety and efficacy of catheter mediated AdVEGF-D regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
Primary objectives:
To test the efficacy of the therapy to improve functional capacity using 6 minute walking test after 6 months follow-up and improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class.
Secondary objectives:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •informed consent signed
- •age > 30 but < 85 years
- •significant angina pectoris (CCS 2-3) despite of optimal medication
- •significant stenosis (> 60%) in coronary angiography (< 6 months)
- •contraindication to CABG or PCI due to diffuse or distal stenosis, chronic total occlusion, vessels with difficult anatomy, stenosis with severe calcifications and stenosis in small vessels (<2.5 mm))
- •angina pectoris or equivalent symptoms in the 6-minute walking exercise test
- •left ventricle wall > 8 mm detected by transthoracic echocardiography or magnetic resonance imaging (treatment area)
排除标准
- •women in fertile age
- •diabetes mellitus with severe complications such as diabetic retinopathy or nephropathy
- •clinically significant anemia (hemoglobin count < 120 mg/l in male, < 110 mg/l in female; hematocrit < 0.36), leukopenia (b-leukocyte count < 3.0x109/l), leukocytosis (b-leukocyte count > 12.0x109/l) or thrombocytopenia (b-thrombocyte count < 100x109/l)
- •renal insufficiency (P-creatinine > 160 mg/l)
- •liver insufficiency (P-alanine aminotransferase or P-alkaline phosphatase over 2 x normal)
- •haematuria of unknown origin
- •severe hypertension (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg) or significant hypotension (systolic blood pressure < 90 mmHg)
- •significant obesity (Body Mass Index > 35)
- •acute infection
- •immunosuppressive medication
- •significant impairment of left ventricular function (ejection fraction < 25% in echocardiography)
- •symptomatic congestive heart failure (New York Heart Association class 3-4)
- •haemodynamically significant (grade 3-4/4) aortic or mitral regurgitation or other heart disease needing surgery
- •recent (< 6 weeks) acute coronary syndrome or myocardial infarction, PCI or CABG, stroke or transient ischemic attack (TIA)
- •current or suspected malignancy
研究组 & 干预措施
AdvVEGF-D
Intramyocardial AdVEGF-D
干预措施: AdvVEGF-D (Drug)
Control
Intramyocardial placebo (buffer solution without gene)
干预措施: Control Rx (Drug)
结局指标
主要结局
Severity of angina pectoris symptoms at 6 months
时间窗: 6 months after gene transfer
Relieve of angina symptoms 6 months after the treatment (CCS class)
Functional capacity at 6 months
时间窗: 6 months after gene transfer
Improvement of exercise capacity 6 months after the treatment as measured by 6 minute walking test (walking distance in meters)
次要结局
- Severity of angina pectoris symptoms at 12 months(Time Frame: 12 months after gene transfer)
- Adverse cardiac events at 6 and 12 months(6 and 12 months after gene transfer)
- Quality of Life (Short-Form Health Survey) at 6 and 12 months(6 and 12 months after gene transfer)
- Quality of Life (EQ-5) at 6 and 12 months(6 and 12 months after gene transfer)
- Functional capacity at 12 months(12 months after gene transfer)
- Quality of Life (Seattle Angina Questionnaire ) at 6 and 12 months(6 and 12 months after gene transfer)
- Angina pectoris medication at 6 and 12 months(6 and 12 months after gene transfer)
- Myocardial perfusion at 6 months(6 months after gene transfer)