Multicenter Prospective Randomized Double Blind Trial of Bone Marrow Mononuclear Cells Transplantation Through Intracoronary Injection in Patients With Acute Myocardial Infarction.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 166
- 试验地点
- 2
- 主要终点
- Global Left Ventricular Ejection Fraction change
研究概览
简要总结
The purpose of this study is to determine cell therapy efficacy in patients with ST elevation acute myocardial infarction (STEMI)
详细描述
This study protocol describes a randomized double blind clinical trial, which main purpose is to evaluate the effect of the autologous bone marrow mononuclear cell (ABMMC) implant in 300 Brazilian patients with ST elevation acute myocardial infarction (STEMI).
Double blind study design was chosen for this trial, based on several phase I and II safety trials of intracoronary autologous bone marrow stem cells transplantation, already published. The study coordinator committee, supported by the Brazilian Health Ministry, therefore has proposed a phase III trial with the purpose of proving the efficacy of this kind of therapy, for a population with a high risk of developing heart failure and of death by cardiovascular cause.
Thus, in this protocol we propose a prospective, double blind, controlled and randomized trial to evaluate the effect of ABMMC transplantation through intracoronary infusion, on systolic left ventricle (LV) function. The main hypothesis of this trial is that patients submitted to autologous bone marrow stem cell implant, after 6 months follow up, will present a 5% relative increase of the ejection fraction (EF) comparing to control group.
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
Control group received injection of saline with 5% autologous serum without the suspension of mononuclear cells.
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients will be eligible if presenting all characteristics described below:
- •ST segment elevation myocardial infarction in two or more contiguous leads, and according to the WHO definition, at least one of the following two:
- •i) Presence of chest pain. ii) Elevation of the myonecrosis markers.
- •Age between 30 and 80 years old.
- •Ejection fraction ≤50% on Echocardiogram (Simpson) and segmentary dysfunction of the infarction area, measured between the 3rd and 5th day post AMI.
- •Among patients submitted to thrombolytic therapy, the angioplasty of the related artery should be preferably done up to 24h after thrombolysis, with a maximum deadline of 72h after thrombolysis.
排除标准
- •Patients will be ineligible if presenting any of the characteristics described below:
- •AMI related artery presenting TIMI < 3 at the moment f cell injection.
- •Left Main Coronary Artery Lesion of >50% or multivessel coronariopathy (>70% lesion in vessels with >2,0mm diameter in left anterior descending, circumflex and right coronary territory) indicating the need for CABG or angioplasty with three or more stents implant.
- •Coronary anatomy, after thrombolytic reperfusion, presenting no need for angioplasty with stent implant.
- •Final Diastolic Pression of the LV higher than 30 mmHg during ventriculography for evaluating EF inclusion criteria for the research protocol (item "c" of inclusion criteria).
- •Cardiac arrest or Killip IV AMI at admission with need of ventilatory support.
- •Cardiogenic shock persisting up to the third day after AMI (with need of Intra-aortic balloon pump or vasopressors).
- •AMI mechanical complications (ventricular septal defect, papillary muscle rupture, and left ventricular free wall rupture).
- •Significant valve disease, defined as aortic stenosis (mean systolic pressure gradient across the aortic valve >50mmHg), mitral stenosis with a valvar area less than 1,5 cm,2 moderate to severe aortic and/or mitral regurgitation.
- •Chronic use of immunosuppressive agents.
- •> 2,0 mg/dl creatinine or previous dialysis treatment.
- •Presence of fever on the past 48h before injection glaring active systemic infection according to ACCP/SCCM (American College of Chest Physicians/Society of Critical Care Medicine) sepsis definition.
- •Sustained ventricular tachycardia 48h after AMI.
- •Illicit drugs abuse or alcohol abuse (based on DSM IV).
- •Any co morbidity, with survival impact in two years.
- •Myocarditis
- •Active liver disease
- •COPD in continuous steroids use.
- •Hematological disease, neoplasm, bone disease or hemostatic disturbances.
- •Inflammatory disease or chronicle infectious disease.
- •Presence of definitive implantation of a cardiac pace maker or cardiac defibrillator.
- •Impossibility to reach a cells suspension of 100 million mononuclear cells due to cells paucity in the bone marrow aspirate.
结局指标
主要结局
Global Left Ventricular Ejection Fraction change
时间窗: 6 months
次要结局
- Acute myocardial infarction, stroke and hospital admission due to cardiovascular cause(30 days, 90 days, 6 months and 1 year)
- Regional wall motion, wall thickening, and volume of late contrast enhancement(Baseline and 6 months)
- Cost-effectiveness and cost-utility evaluation of autologous bone marrow mononuclear cells implant versus conventional treatment(1 year)
- Death(30 days, 90 days, 6 months and 1 year)
- Reintervention of the AMI related artery and of the non-related artery(30 days, 90 days, 6 months and 1 year)
- Evolutive alterations of the coronarian anatomy, as well as the patency of the coronary stents(6 months)
- Quality of life assessment using the Short-Form 36, Minnesota Living with Heart Failure Questionnaire and Seattle Angina questionnaire(Baseline, 6 months and 1 year)
研究者
Hans Fernando Rocha Dohmann
MD, PhD
Pro-Cardiaco Hospital