The IMPlantation of Autologous CD133+ sTem Cells in Patients Undergoing CABG With Left Ventricular Dysfunction: the IMPACT-CABG Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Freedom from Major Adverse Cardiac Event: cardiac death, myocardial infarct, repeat coronary bypass grafting or percutaneous intervention of bypassed artery.
研究概览
简要总结
Following myocardial infarct, cellular therapy is a potential approach to repopulate the injured myocardium, to treat heart failure and restore cardiac function. The purpose of this study is to assess the safety, feasibility and efficacy of intramyocardial delivery of selected autologous CD133+ bone marrow stem cells at time of coronary artery bypass grafting in patients with chronic ischemic cardiomyopathy.
详细描述
CD133+ are well-characterized distinct early progenitor group of stem cells that possess high engraftment, pluripotent and angiogenic capacity and proved to be valuable for cardiac repair by promoting neovascularization, inhibition of apoptosis and cardiomyogenesis.
Our proposed research protocol involves patients with chronic ischemic heart disease and left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). In this phase II clinical trial, prospective, randomized, 2 arm, double-blind, placebo-controlled study, we will assess the safety, feasibility and functional effect of intra-myocardial injection of highly selected autologous CD133+ bone marrow stem cells to placebo.
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)
盲法说明
double blind
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
- •Age ≥18 years, and ≤75 years.
- •Patients with severe chronic ischemic cardiomyopathy manifested by Canadian Cardiovascular Society (CCS) class II or greater angina, and/or New York Heart Association (NYHA) class II or greater, AND who have undergone diagnostic coronary angiography demonstrating ≥70% diameter narrowing of at least 2 major coronary arteries or branches or ≥50% diameter narrowing of the left main coronary artery.
- •A significant left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction ≤45% but ≥25%) due to prior myocardial infarction. This area of left ventricular dysfunction should be akinetic or severely hypokinetic, not dyskinetic or aneurismal, when assessed by echocardiography or LV angiogram. This territory should be irrigated by one or a branch of the three major vascular territories (i.e. right coronary artery, left circumflex, or left anterior descending artery distribution) that will be bypassed during the surgical procedure.
- •No contraindications or exclusions (see below).
- •Willingness to participate and ability to provide informed consent.
排除标准
- •Contraindications to magnetic resonance imaging including presence of an implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM), or cases in which it is anticipated that an ICD or PPM will be implanted prior to the 6 month follow-up (thus precluding performance of follow-up MR scans), claustrophobia.
- •Lack of ischemic symptoms (angina) prior to referral for CABG (i.e., patients with only 'silent' ischemia will be excluded).
- •Need for urgent or emergent revascularization.
- •Need for concomitant surgical procedure at the time of CABG (e.g. valve repair or replacement, aneurysm resection, etc.).
- •Hemodynamically unstable patients, as defined by heart rate ≤40/min or ≥100/min, and/or systolic blood pressure <90 mmHg or ≥200 mmHg, and/or ongoing need for intravenous inotropic or vasopressor medications.
- •Patients with confirmed myocardial infarction within 14 days, and/or rising cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.
- •Prior CABG surgery.
- •Stroke within 3 months prior to planned CABG.
- •Immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
- •Severe chronic renal insufficiency (serum creatinine ≥ 200 mmol/dl or need for dialysis), liver disease, (diagnosis of cirrhosis, chronic hepatitis, or elevation of serum transaminases ≥3 times the upper limit of normal), cerebrovascular disease requiring concomitant carotid endarterectomy, peripheral arterial disease (claudication as the primary factor limiting activity), active non-dermatological malignancy requiring on-going treatment, or any other condition that would place the patient at increased risk for complications in the judgment of the attending cardiologist or cardiac surgeon
- •Contra-indication for bone marrow aspiration (Thrombocytopenia <50.000 mm3, INR >2.0, use of antiplatelet agents other than aspirin).
- •Hemoglobin less than 10g/dL, white blood cell count less than 4,000/mm3, absolute neutrophil count less than 1500/mm3
- •Active infection, with a temperature greater than 37.5°C within 48 hrs prior to surgery and an unexplained white blood cell count in excess of 10,000/mm3
- •Myelodysplastic syndrome (MDS)
- •Significant cognitive impairment
- •Any condition associated with a life expectancy of less than 6 months
- •Patients known allergic reaction or contraindication to any of the component of the CD133+ enriched cells
- •Participation in other studies
- •History of severe ventricular tachy-arrythmias
- •Positive laboratory test results for syphilis, HIV, HBC, HCV, HTLV1 and HTLV2
- •Pregnant woman
- •Inability or unwillingness to provide written informed consent
研究组 & 干预措施
Placebo
Saline solution with autologous plasma.
干预措施: Injection of stem cells at time of coronary artery bypass grafting (Procedure)
CD133+ stem cells
Autologous CD133+ intramyocardial injection at time of coronary artery bypass grafting.
干预措施: Injection of stem cells at time of coronary artery bypass grafting (Procedure)
结局指标
主要结局
Freedom from Major Adverse Cardiac Event: cardiac death, myocardial infarct, repeat coronary bypass grafting or percutaneous intervention of bypassed artery.
时间窗: 6 months
Freedom from major arrhythmia: sustained ventricular tachycardia or survived sudden death.
时间窗: 6 months
次要结局
- Regional myocardial perfusion and function assessed by magnetic resonance scans.(6 months)
- Device performance end point: Feasibility to produce from 100ml of bone marrow aspiration a final cell product that contains a target CD133+ cells higher than 0.5 million with a purity superior to 30% and a recovery superior to 10%.(Baseline)
- On symptom severity and quality of life after CABG surgery.(6 months)