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: 8214500
• 负责人: JAY H TRAVERSE
• 金额: $ 56.8万
• 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/8214500
• 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; Modification; 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; public health relevance; 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)： 经血管成形术和支架置入术(PCI)快速恢复闭塞冠状动脉血流是缩小ST段抬高型心肌梗死(STEMI)梗死面积的最有效的治疗方法。然而，再灌注也可能与心肌和血管系统的进一步损伤有关，这种损伤可能与最初的缺血性损伤一样严重。尽管STEMI的治疗取得了重大进展，但许多患者仍然会有严重的心肌损伤，并发展为充血性心力衰竭(CHF)，这是该国入院诊断的主要疾病。在STEMI环境下减轻再灌注损伤可显著改善左心功能，减少CHF的发生。然而，在这种情况下发展新的心肌保护形式却严重不足。最近，一种改进的再灌流技术被引入以减少再灌流损伤，称为后处理(PostC)。这利用了一系列短暂的动脉闭塞(30 S)，然后再灌注(30 S)在几个周期中，在闭塞的动脉再灌注后立即开始。这项技术被证明可以在60分钟的冠状动脉闭塞后将犬的心肌梗死面积减少44%。这项技术很容易转移到STEMI患者的直接经皮冠状动脉介入治疗中，使用PTCA球囊控制再灌注。来自我们诊所和其他几个小型临床试验的初步数据表明，PostC也可以减少患者的梗塞面积。然而，目前还没有长期的研究来检验在急性期后是否仍能保持缩小梗塞面积的最初益处。这项建议描述了一项在120名STEMI患者中进行的单中心II期随机临床试验，这将大大增加我们对PostC的有效性和机制的了解。参加这项试验的患者将来自我们的1级急性心肌梗死计划；这是一个全国公认的区域转移系统，涉及明尼苏达州的36家医院。该计划每年治疗约500名STEMI患者。通过使用心脏MRI来评估梗死范围、心肌挽救和微血管阻塞的程度，该方案将显著改善先前的研究，微血管阻塞是不良左室重构的有力预测因素。患者将在第3-5天、3个月和12个月接受MRI评估，以确定这种干预的最初描述的好处是否会持续一段时间，目前尚不清楚。我们将探索几个细胞标记物的变化，这些标记物将揭示Post C的益处机制，包括亚硝酸盐阴离子(一氧化氮)、硫化氢和活性氧物种的测量。PostC的发现缩小了梗死范围，改善了心肌挽救，从而导致左心功能的持续改善，这将代表着STEMI患者治疗的显著进步，并带来显著的公共健康利益。此外，这种干预可以在不对患者或机构造成额外费用的情况下进行。 公共卫生相关性： 项目简介虽然在急性心肌梗死期间恢复冠脉血流(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，它可能会导致进一步的心肌损伤。我们的临床试验将调查在3个月和12个月时，通过心脏MRI测量，使用一种名为后处理的技术来修改再灌注是否会缩小心肌梗死的范围并改善左心功能。