A Phase I/II, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Mesenchymal or the Combination of MSC and Cardiac Stem Cells) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Incidence of any treatment emergent serious adverse events (TE-SAEs)
研究概览
简要总结
Before initiating the full randomized study, a Pilot Safety Phase will be performed. In this phase the composition of cells administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested. The randomized portion of the study will be conducted after a full review of the safety data from the pilot Phase by the Data safety monitoring board.
Following the Pilot Phase of five (5) Fifty (50) patients scheduled to undergo cardiac catheterization and meeting all inclusion/exclusion criteria will be evaluated at baseline.
Patients will be randomized in a 2:2:1 ratio to one of three Treatment Strategies.
详细描述
A Phase I/II, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Mesenchymal or the combination of MSC and Cardiac Stem Cells) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.
A total of 55 subjects participating, with 5 in the pilot phase and 50 in the randomized phase.
Patients with chronic ischemic left ventricular dysfunction and heart failure secondary to MI scheduled to undergo cardiac catheterization.
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
- Single (Participant)
入排标准
- 年龄范围
- 21 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to participate in this study, a patient MUST:
- •Be ≥ 21 and < 90 years of age.
- •Provide written informed consent.
- •Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by the following: Screening MRI must show an area of akinesis, dyskinesis, or severe hypokinesis associated with evidence of myocardial scarring based on delayed hyperenhancement following gadolinium infusion.
- •Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 month.
- •Be a candidate for cardiac catheterization.
- •Have an ejection fraction ≤ 50% by gated blood pool scan, two-dimensional echocardiogram, cardiac MRI, or left ventriculogram within the prior six months and not in the setting of a recent ischemic event.
排除标准
- •In order to participate in this study, a patient MUST NOT:
- •Have a baseline glomerular filtration rate < 50 ml/min1.73m
- •Have a known, serious radiographic contrast allergy.
- •Have a mechanical aortic valve or heart constrictive device.
- •Have a documented presence of aortic stenosis (aortic stenosis graded as ≥ +2 equivalent to an orifice area of 1.5cm2 or less).
- •Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
- •Require coronary artery revascularization. Patients who require or undergo revascularization procedures should undergo these procedures a minimum of 3 months in advance of treatment within this study. In addition, patients who develop a need for revascularization following enrollment will be submitted for this therapy without delay.
- •Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete heart block) or QTc interval > 550 ms on screening ECG.
- •AICD firing in the past 60 days prior to the procedure.
- •Have unstable angina within 2 weeks of the planned procedure.
- •Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation.
- •Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
- •Have a coagulopathy = (INR > 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR < 1.
- •Patients who cannot be withdrawn from Coumadin will be excluded from enrollment
- •Have known allergies to penicillin or streptomycin.
- •Have a contra-indication to performance of an MRI scan.
- •Be an organ transplant recipient.
- •Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
- •Have a non-cardiac condition that limits lifespan to < 1 year.
- •Have a history of drug or alcohol abuse within the past 24 months.
- •Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists.
- •Be serum positive for HIV, hepatitis BsAg or hepatitis C.
- •Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
- •Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.
研究组 & 干预措施
Group A - Autologous hMSCs
Autologous hMSCs: 40 million cells/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 2 x 10^8 (200 million) hMSCs. The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
干预措施: Autologous hMSCs (Drug)
Group A - Autologous hMSCs
Autologous hMSCs: 40 million cells/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 2 x 10^8 (200 million) hMSCs. The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
干预措施: Biosense Webster MyoStar NOGA Injection Catheter System (Device)
Group B - Autologous Human C-Kit CSCs II
Autologous hMSCs PLUS autologous C-Kit hCSCs: Mixture of 39.8 million hMSCs and 0.2 million C-Kit hCSCs/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 1.99 x 10^8 (199 million) hMSCs and 1 million C-Kit hCSCs.The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
干预措施: Autologous Human C-Kit CSCs II (Drug)
Group B - Autologous Human C-Kit CSCs II
Autologous hMSCs PLUS autologous C-Kit hCSCs: Mixture of 39.8 million hMSCs and 0.2 million C-Kit hCSCs/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 1.99 x 10^8 (199 million) hMSCs and 1 million C-Kit hCSCs.The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
干预措施: Biosense Webster MyoStar NOGA Injection Catheter System (Device)
Placebo
Placebo (ten 0.5 ml injections of phosphate-buffered saline [PBS] and 1% human serum albumin [HSA]).The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
干预措施: Placebo (Drug)
Placebo
Placebo (ten 0.5 ml injections of phosphate-buffered saline [PBS] and 1% human serum albumin [HSA]).The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug.
干预措施: Biosense Webster MyoStar NOGA Injection Catheter System (Device)
结局指标
主要结局
Incidence of any treatment emergent serious adverse events (TE-SAEs)
时间窗: One Month post-catheterization
Incidence (at one month post-catheterization) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise), or atrial fibrillation.
次要结局
- Treatment Emergent adverse event rates(At 6 Month and 12 Month visit)
- Ectopic tissue formation(At 6 Month and 12 Month visit)
- 48-hour ambulatory electrocardiogram (ECG) recordings.(At 6 Month and 12 Month visit)
- Hematology value changes post-catheterization(At 6 Month and 12 Month visit)
- Urinalysis results changes post-catheterization(At 6 Month and 12 Month visit)
- Clinical chemistry values post-catheterization(At 6 Month and 12 Month visit)
- Pulmonary function(At 6 Month and 12 Month visit)
- Serial troponin I values(Every 12 hours for the first 48 hours post-cardiac catheterization)
- Creatine kinase-MB (CK-MB) value changes post-catheterization(Every 12 hours for first 48 hours post-cardiac catheterization)
- Post-cardiac catheterization echocardiogram.(Day 1 Post Echocardiogram)
- Magnetic resonance imaging (MRI) measures of infarct scar size (ISS)(At 6 Month and 12 Month visit)
- Echocardiographic measures of infarct scar size (ISS)(At 6 Month and 12 Month visit)
- Magnetic resonance imaging (MRI) of Left Regional Ventricular Function(At 6 Month and 12 Month visit)
- Echocardiographic measures of Left Regional Ventricular Function(At 6 Month and 12 Month visit)
- Magnetic resonance imaging (MRI) of Global Ventricular Function(At 6 Month and 12 Month visit)
- Echocardiographic measures of Global Ventricular Function(At 6 Month and 12 Month visit)
- Tissue perfusion measured by MRI.(At 6 Month and 12 Month visit)
- Peak oxygen consumption (Peak VO2) (by treadmill determination).(At 6 Month and 12 Month visit)
- Six-minute walk test.(At 6 Month and 12 Month visit)
- New York Heart Association (NYHA) functional class.(At 6 Month and 12 Month visit)
- Minnesota Living with Heart Failure (MLHF) questionnaire.(At 6 Month and 12 Month visit)
- Incidence of Major Adverse Cardiac Events (MACE)(At 6 Month and 12 Month visit)
研究者
Joshua M Hare
ISCI Director, Chief Science Officer, Senior Assoc. Dean, Louis Lemberg Professor of Medicine
University of Miami