Phase I Trial of Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy (RECARDIO Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Safety
研究概览
简要总结
The purpose of this study is to evaluate whether endocavitary intramyocardial injection of autologous bone-marrow-derived CD133+ cells is safe on the basis of number of adverse events, with follow-up assessments extending up to 1 year after enrolment.
详细描述
This will be a Phase I study investigating the safety and preliminary efficacy of endocavitary injection of bone-marrow-derived CD133+ cells in 15 patients with ischemic heart failure (IHF) not eligible for conventional revascularization. Patients eligible will undergo bone-marrow aspiration. On the day following bone-marrow aspiration patients will undergo fluoroscopy-based endocavitary intramyocardial injections of the target areas previously identified by gated-SPECT/CMR. CD133+ cells suspended in physiological saline supplemented with 5% human albumin solution will be injected into the myocardium via the endocardial route.
After discharge, efficacy follow-up will last 6-months safety follow-up (FU) will be extended up to 1 year.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ischemic heart failure not amenable to any type of revascularization procedure (percutaneous or surgical) as determined by one interventional cardiologist and one cardiovascular surgeon,
- •Canadian Cardiovascular Society Angina functional class III to IV angina and/or symptoms of heart failure (NYHA score IIb to IV) under state-of-the-art maximal medical therapy,
- •Left Ventricular Ejection Fraction between 20% and 45%,
- •Peak V02 ≤ 21 mL/Kg/min,
- •Presence of a reversible perfusion defect ≥ 10% of the left ventricular myocardium (at least 2 segments over 20) as determined by gated-SPECT, 6.18 years ≤ Age ≤ 75 years,
- •7.Hemodynamic stability, 8.Ability to accomplish a cardiopulmonary exercise testing, 9.Are not pregnant and do not plan to become pregnant during the study. Females with childbearing potential must provide a negative pregnancy test within 1-7 days before intervention and must be using oral or injectable contraception (non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start), 10.A signed consent form that has been approved by the institutional review board.
排除标准
- •A high-risk acute coronary syndrome (ACS) or a myocardial infarction in the past 3 months,
- •Presence of a documented unstable angina,
- •Left ventricular thrombus, as documented by echocardiography,
- •Evidence of a life-threatening arrhythmia,
- •Presence of any severe mitral valve disease requiring valve replacement or reconstruction,
- •Presence of a mechanical aortic valve,
- •Presence of stenosis of the aortic valve, graded as ≥+2 equivalent to an orifice area of 1,5 cm2 or less,
- •Presence of moderate to severe insufficiency of the aortic valve,
- •A left ventricular wall thickness of <8 mm at the target site for cell injection, as assessed by 2-D echocardiography and/or cardiac MRI,
- •Have a known, serious radiographic contrast allergy,
- •Contraindications to bone-marrow aspiration,
- •Be an organ transplant recipient,
- •Have liver dysfunction, as evidenced by enzymes (AST,ALT) >3x the upper limits of normals,
- •Severe renal failure (creatinine plasma levels > 2.5 mg/dl),
- •A bleeding diathesis (defined as an INR greater than 1,5 not because of a reversible cause, i.e. warfarin),
- •Have an hematologic abnormality without other explanation,
- •Apparent infection (c-reactive protein (CPR)>30 mg/L, fever > 37 °C),
- •An infectious-disease test result positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, treponema pallidum (VDRL), HTLV 1 and 2,
- •Previous or current documented history of leukemia, myeloproliferative or myeloplastic disorders,
- •Have a cardiac condition that limits lifespan to <1 y,
- •A history of malignancy in the past 5 years,
- •Have a history of drug or alcoholic abuse within the past 24 months,
- •Be on chronic therapy with immunosuppressants,
- •Pregnant or lactating status,
- •Any condition that, in the judgment of the investigator, would place the patient at undue risk.
结局指标
主要结局
Safety
时间窗: 1 year
The primary objective of this study will be to evaluate whether endocavitary intramyocardial injection of autologous bone-marrow-derived CD133+ cells is safe on the basis of number of adverse events, with follow-up assessments extending up to 1 year after enrolment.
次要结局
- Efficacy(6 months)
研究者
Giulio Pompilio
MD PhD
Centro Cardiologico Monzino