Phase 2 Study of SERCA2a Gene Transfer in Patients With Severe Heart Failure
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- left ventricular end-systolic volume measured by CT-Scan
研究概览
简要总结
The purpose of this study is to determine the effect of intracoronary SERCA2a Gene transfer on cardiac volumes and function using multimodality cardiac imaging.
详细描述
The purpose of gene transfer of SERCA2a is to improve systolic and diastolic function of the failing ventricle. Studies show that reduction of SERCA2a in failing ventricle is a key factor in depression of contraction, and that restoration of SERCA2a levels can improve left ventricular function and remodeling. The aim of the study is to investigate the effect of an adeno-associated viral vector expressing the sarcoplasmic reticulum calcium ATPase (SERCA2a), driven by the CMV promoter (AAV1-CMV-SERCA2a), on the ventricular remodeling of patients with severe heart failure using multimodality cardiac imaging. This is a Phase 2 monocenter double blind randomized placebo-controled, parallel study. The study will enroll 44 symptomatic heart failure patients with NYHA IIIb/IV, with left-ventricular ejection fraction of 35% or less receiving an optimal standard medical therapy. The absence of neutralizing antibodies against AAV1 will be primarily checked. Seronegative patients will be randomized to receive either 1x10e13 AAV1-CMV-Serca2a or a placebo as a single intracoronary infusion. Evolution during the next 6 months of the left ventricular end-systolic volume (measured with a 256-slices CT-scan before injection and 6 months later) will be the primary endpoint. Secondary endpoints will include changes in the LVEF, diastolic volumes, VO2max, Echocardiographic remodeling, BNP, cardiac hemodynamics and biological safety profile.
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
- Double (Participant, Investigator)
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
- •Patients with NYHA class III / IV severe heart failure ≥ 3 months
- •Ischemic or non-ischemic origin
- •Left ventricular ejection fraction ≤35%
- •Patients must be receiving optimal (maximum tolerated doses) medical treatment (diuretics, renin-angiotensin-aldosterone system blockers, beta blockers, ±Ivabradine) for at least 1 month (with the exception of diuretic dose titration) and must be stable.
- •No decompensated congestive heart failure within the past month
- •With or without an ICD if the ICD was implanted over 3 months ago, with or without biventricular pacing if the RCT was implanted over 6 months ago
- •All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational medicinal product
- •Patient must have given written informed consent to participate in this study
排除标准
- •<18 or >80 years old
- •AAV1 seropositivity (titer <1:2) in the last 3 months
- •Atrial fibrillation in the absence of permanent ventricular pacing
- •Coronary revascularization or heart surgery or pacemaker implantation < 3 months
- •Ischemic heart disease without at least one coronary artery with a TIMI-3 flow
- •Restrictive cardiomyopathy, hypertrophic obstructive cardiomyopathy, pericardial disease, cardiac amyloidosis
- •Heart transplant, an already implanted or needing to urgently implant external ventricular assist device
- •Myocardial infarction (STEMI or NSTEMI) < 3 months
- •Treatment with intravenous positive inotropic agents or diuretics in the past 28 days
- •Pregnant or nursing patient
- •Female patient of childbearing age with no effective means of contraception
- •Severe renal failure defined by a creatinine clearance of < 30 mL/min (last bloodwork done less than 6 months)
- •Liver failure, chronic liver disease or laboratory tests > 3 x N (AST, ALT, ALP))(last bloodwork done less than 6 months)
- •Thrombocytopenia (<50,000/mm3
- •Patient treated with immunosuppressants, has an immunodeficiency or whose neutrophil count < 1000 mm3
- •Recent sepsis (< 3 months)
- •Active neoplasia or treated < 5 years
- •No medical insurance
- •Patient is enrolled in another randomized study
- •Patient does not understand the protocol procedures sponsor suspects poor compliance with the protocol
结局指标
主要结局
left ventricular end-systolic volume measured by CT-Scan
时间窗: at 6 months
left ventricular end-systolic volume measured by CT-Scan / changes from baseline to 6 months
次要结局
- Number of hospitalized patients for worsening heart failure(at 6 and 12 months)
- CT-scan other measurments: left ventricular end-diastolic volume(at 6 and 12 months)
- Cardiac volumes and function(at 6 and 12 months)
- Cardiac function assessed by echocardiography(at 6 and12 months)
- NT-ProBNP(at 6 and12 months)
- Cardiac hemodynamic parameters(at 6 months)
- VO2 max(at 6 and 12 months)
- Quality of Life (Kansas city score)(at 3,6,9,12 months)
- Time to cardiovascular event(at 6 and 12 months)
- Cardiac volumes assessed by echocardiography(at 6 and12 months)
- CT-scan other measurments: left ventricular end-systolic volume(12 months)