Phase II Clinical Trial to Evaluate the Benefits of Postconditioning in STEMI

评估 STEMI 后处理益处的 II 期临床试验

• 批准号: 8051374
• 负责人: JAY H TRAVERSE
• 金额: $ 59.25万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051374
• 关键词: Acute; Acute myocardial infarction; Admission activity; Angioplasty; Animal Model; Anions; Apoptosis; Area; Arteries; Biological Availability; Biological Preservation; Blood flow; Canis familiaris; Cardiac; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical trial protocol document; Congestive Heart Failure; Coronary; Coronary Occlusions; Coronary artery; Country; Data; Development; Diagnosis; Effectiveness; Enrollment; Evaluation; Functional disorder; Gold; Health Benefit; Heart; Hospitals; Hydrogen Sulfide; Image; Infarction; Injury; Institutes; Institutional Review Boards; Intervention; Ischemia; Left Ventricular Function; Left Ventricular Remodeling; Light; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Mediator of activation protein; Minnesota; Molecular; Myocardial; Myocardial Infarction; Myocardium; Nitric Oxide; Nitrites; Obstruction; Patients; Percutaneous Transluminal Coronary Angioplasty; Phase; Phase II Clinical Trials; Plasma; Play; Production; Protocols documentation; Public Health; Randomized Clinical Trials; Reactive Oxygen Species; Reperfusion Injury; Reperfusion Therapy; Risk; Role; Series; Signal Transduction; System; Techniques; Time; Tissues; Translating; Universities; Water; Weight; abstracting; artery occlusion; cost; effective therapy; follow-up; improved; indexing; myocardial infarct sizing; novel; pre-clinical; programs; response; restoration; standard measure

DESCRIPTION (provided by applicant): Project Summary/Abstract Rapid restoration of blood flow of an occluded coronary artery by angioplasty and stenting (PCI) is the most effective therapy for reducing infarct size in ST-segment elevation myocardial infarction (STEMI). However, reperfusion may also be associated with further injury to the myocardium and vasculature that can be as significant as the initial ischemic insult. Despite significant advances in the treatment of STEMI, many patients will still have significant myocardial injury and develop congestive heart failure (CHF), the leading hospital admission diagnosis in this country. Reducing reperfusion injury in the setting of STEMI may significantly improve left-ventricular (LV) function and reduce the development of CHF. However, the development of novel forms of myocardial protection in this setting has been grossly underutilized. Recently, a modified reperfusion technique to reduce reperfusion injury was introduced called postconditioning (PostC). This utilizes a series of brief (30 s) occlusions of the artery followed by reperfusion (30 s) over several cycles which commences immediately upon reperfusion of the occluded artery. This technique was demonstrated to reduce infarct size in dogs by 44% following a 60 minute coronary occlusion. This technique is easily transferred to the setting of primary PCI in patients with STEMI using a PTCA balloon to control reperfusion. Preliminary data from our clinic and several other small clinical trials suggest that PostC may also reduce infarct size in patients. However, there are no long- term studies to examine if the initial benefit on infarct size reduction is maintained beyond the acute period. This proposal describes a single center Phase II, randomized clinical trial in 120 patients with STEMI that will greatly increase our understanding of the effectiveness and mechanisms of PostC. Patients enrolled in this trial will come from our Level 1 Acute MI Program; a nationally recognized regional transfer system involving 36 hospitals in Minnesota. This program treats approximately 500 STEMI patients per year. This protocol will significantly improve upon previous studies by using cardiac MRI to evaluate infarct size, myocardial salvage and degree of microvascular obstruction, which is a strong predictor of adverse LV remodeling. Patients will undergo MRI evaluations at Day 3-5, 3 months and 12 months to ascertain if the initial described benefit of this intervention is sustained over time which is currently not known. We will explore the changes in several cellular markers that will shed light on the mechanisms of benefit of Post C including measurements of nitrite anion (nitric oxide), hydrogen sulfide and reactive oxygen species. The findings that PostC reduces infarct size and improves myocardial salvage that results in sustained improvement in LV function would represent a marked advancement in the treatment of STEMI patients and result in a significant public health benefit. Furthermore, this intervention can be performed at no additional cost to the patient or facility. PUBLIC HEALTH RELEVANCE: Project Narrative Although the restoration of coronary blood flow (reperfusion) during an acute myocardial infarction is the most rapid way of stopping ongoing myocardial injury, it may result in further myocardial damage as a result of reperfusion injury. Our clinical trial will investigate if the modification of reperfusion using a technique called Postconditioning will reduce the size of a myocardial infarction and improve LV function as measured by cardiac MRI at 3 and 12months.

描述（由申请人提供）： 通过血管成形术和支架（PCI）对闭塞冠状动脉的血流的项目摘要/抽象快速恢复是减少ST段升高升高心肌梗塞（STEMI）的最有效疗法。但是，再灌注也可能与对心肌和脉管系统的进一步损伤有关，这可能与初始缺血性损伤一样重要。尽管STEMI的治疗方面取得了重大进展，但许多患者仍会造成严重的心肌损伤并发展充血性心力衰竭（CHF），这是该国领先的住院诊断。在STEMI的情况下，减少再灌注损伤可能会显着改善左心室（LV）功能并减少CHF的发展。但是，在这种情况下，新型心肌保护形式的发展被严重充分利用。 最近，引入了一种减少再灌注损伤的经过改进的再灌注技术，称为后条件（Postc）。这利用了一系列简短的（30 s）动脉阻塞，然后在几个循环中再灌注（30 s），这些周期立即在闭塞动脉再灌注后立即开始。在60分钟的冠状动脉阻塞后，该技术已证明这项技术可将狗的梗塞大小降低44％。使用PTCA球囊控制再灌注的STEMI患者，该技术很容易转移到STEMI患者的主要PCI设置中。我们诊所和其他几项小型临床试验的初步数据表明，Postc也可能会降低患者的梗死大小。但是，尚无长期研究来检查最初对梗塞大小减小的益处是否维持在急性时期之后。 该提案描述了120名STEMI患者的单个中心II期，随机临床试验，这将大大增加我们对Postc的有效性和机制的理解。参加此试验的患者将来自我们的1级急性MI计划；一个全国认可的区域转会系统，涉及明尼苏达州的36家医院。该计划每年对大约500名STEMI患者进行治疗。通过使用心脏MRI评估梗塞大小，心肌救助和微血管阻塞程度，该方案将显着改善先前的研究，这是不良LV重塑的有力预测指标。患者将在第3-5天，3个月零12个月进行MRI评估，以确定此干预措施的初始描述益处是否会随着时间的推移持续而持续，目前尚不清楚。 我们将探索几个细胞标记的变化，这些变化将阐明C后C的益处机理，包括亚硝酸盐阴离子（一氧化氮），硫化氢和活性氧。 PostC降低梗塞大小并改善心肌挽救的发现，从而持续改善LV功能，这将代表对STEMI患者的治疗方面的明显进步，并带来巨大的公共卫生益处。此外，这种干预措施无需为患者或设施而进行额外的费用。 公共卫生相关性： 项目叙事尽管在急性心肌梗塞期间恢复冠状动脉血流（再灌注）是阻止持续心肌损伤的最快方法，但由于再灌注损伤，可能导致进一步的心肌损害。我们的临床试验将调查使用称为后条件的技术对再灌注的修饰是否会减少心肌梗死的大小，并改善3和12个月中心脏MRI测量的LV功能。