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）： 项目摘要/摘要 通过血管成形术和支架置入术 (PCI) 快速恢复闭塞冠状动脉的血流是减少 ST 段抬高型心肌梗死 (STEMI) 梗塞面积的最有效疗法。然而，再灌注也可能与心肌和脉管系统的进一步损伤有关，其程度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，但许多患者仍会出现严重的心肌损伤并发展为充血性心力衰竭 (CHF)，这是该国主要的入院诊断。减少 STEMI 情况下的再灌注损伤可能会显着改善左心室 (LV) 功能并减少 CHF 的发生。然而，在这种情况下新型心肌保护形式的开发尚未得到充分利用。 最近，引入了一种减少再灌注损伤的改良再灌注技术，称为后处理（PostC）。这利用了一系列短暂（30秒）的动脉闭塞，然后在几个周期内进行再灌注（30秒），该循环在闭塞动脉再灌注后立即开始。经证明，该技术可使犬冠状动脉闭塞 60 分钟后的梗塞面积减少 44%。该技术很容易转移到 STEMI 患者的直接 PCI 中，使用 PTCA 球囊控制再灌注。我们诊所和其他几项小型临床试验的初步数据表明，PostC 还可以减少患者的梗塞面积。然而，目前尚无长期研究来检验梗塞面积缩小的初始益处是否能在急性期后维持。 该提案描述了一项针对 120 名 STEMI 患者的单中心 II 期随机临床试验，这将大大增加我们对 PostC 有效性和机制的理解。参加本次试验的患者将来自我们的 1 级急性心肌梗死项目；全国认可的区域转运系统，涉及明尼苏达州 36 家医院。该计划每年治疗大约 500 名 STEMI 患者。该方案将通过使用心脏 MRI 来评估梗塞大小、心肌抢救和微血管阻塞程度（这是不良 LV 重塑的有力预测因子），从而显着改进之前的研究。患者将在第 3-5 天、3 个月和 12 个月接受 MRI 评估，以确定这种干预措施最初描述的益处是否能随着时间的推移而持续，目前尚不清楚。 我们将探讨几种细胞标记物的变化，这些变化将揭示 Post C 的益处机制，包括测量亚硝酸根阴离子（一氧化氮）、硫化氢和活性氧。 PostC 减少梗塞面积并改善心肌挽救，从而持续改善左心室功能，这一发现将代表 STEMI 患者治疗的显着进步，并带来重大的公共健康益处。此外，这种干预无需患者或机构承担额外费用即可进行。 公共卫生相关性： 项目叙述虽然急性心肌梗死期间冠状动脉血流的恢复（再灌注）是停止持续心肌损伤的最快速方法，但它可能因再灌注损伤而导致进一步的心肌损伤。我们的临床试验将调查使用后处理技术改变再灌注是否会减少心肌梗塞的范围并改善 3 个月和 12 个月时通过心脏 MRI 测量的左心室功能。