Arrhythmia Assessment Core Lab for IMMEDIATE Trial

描述(由申请人提供)： 我们团队和其他人的基础和临床研究表明，静脉注射葡萄糖、胰岛素和钾(GIK)I代谢性心肌支持可以减少缺血诱导的心律失常、从不稳定型心绞痛(UAP)到急性心肌梗死(AMI)的进展、MI大小和死亡率。此外，对于ST段抬高心肌梗死(STEMI)，GIK可延长冠脉再通受益时间。这些作用将降低急性冠脉综合征(ACS：包括急性心肌梗死和不稳定型心绞痛)的短期和长期死亡率以及心力衰竭(HF)的倾向。这些好处与急性冠脉综合征的早期有关，因为在这种情况下，拯救生命的风险和机会都是最高的。因此，我们建议在急诊初期评估和治疗期间立即进行心肌代谢增强)试验，这是一项在急性冠脉综合征患者中尽早进行即刻GIK的随机安慰剂对照临床试验：在院前紧急医疗服务(EMS)环境中，或者对于那些向急诊科(ED)提出要求的患者，在急诊到达后立即进行。与之前和正在进行的GIK试验不同，这将测试适用于所有急性冠脉综合征(而不仅仅是急性心肌梗死(或STEMI))的GIK，以及它在院前EMS和ED设置中的使用。我们的主要假设是，早期GIK将降低30天和一年的死亡率。主要的次要假设是，GIK可以减少院前/院内心脏骤停、UAP发展为急性心肌梗死，并通过限制心肌梗死的大小，降低发生心力衰竭的倾向。其他假说则阐述了这些效应的机制。该项目将耗时5年：一年的准备和测试操作，28个月的患者招募，然后完成数据收集、分析和报告。临床站点将设在马萨诸塞州、德克萨斯州和威斯康星州；该应用程序用于塔夫茨-新英格兰医疗中心的试验协调(附带3个：数据协调中心和2个核心实验室)。纳入15,450名患者(不包括急性心肌梗死Killip级和2级)将提供80%的统计能力，以检测主要终点(30天和1年死亡率)和主要次级终点(心脏骤停或死亡，心衰住院或死亡，以及不稳定型心绞痛向急性心肌梗死的进展)减少25%。对400名受试者进行左心功能、室性心律失常标志物和生化测试的评估，将为GIK和安慰剂之间的临床相关差异提供80%的力量。如果之前的GIK试验中急性死亡率降低30%-50%和HF的减少得到证实，这种廉价的治疗方法可以大大减少美国最常见的死亡和住院原因。(摘要结束。)

DESCRIPTION (provided by applicant): Basic and clinical research by our team and others suggests intravenous glucose, insulin, and potassium (GIK)I metabolic myocardial support reduces ischemia-induced arrhythmias, progression from unstable angina pectoris I (UAP) to acute myocardial infarction (AMI), MI size, and mortality. Also, for ST elevation MI (STEMI), GIK may prolong time of benefit of coronary reperfusion. These effects should reduce short- and long-term mortality from acute coronary syndromes (ACS: including AMI and UAP) and the propensity for heart failure (HF). These benefits are related to the earliness of ACS, when both risk and opportunity to save lives are highest. Thus, we propose the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial, a randomized placebo-controlled clinical trial of immediate GIK as early as possible in ACS: in the prehospital emergency medical service (EMS) setting, or, for those presenting to emergency departments (EDs), immediately upon ED arrival. Distinct from prior and ongoing GIK trials, this will test GIK for all ACS rather than only for AMI (or STEMI), and its use in prehospital EMS and ED settings. Our primary hypothesis is that early GIK will reduce 30-day and 1-year mortality. Major secondary hypotheses posit GIK will reduce pre/in-hospital cardiac arrest, progression of UAP to AMI, and by this and limiting MI size, will reduce the propensity for HF. Other hypotheses address mechanisms of these effects. The project will take 5 years: a year preparing and testing operations, 28 months enrolling patients, and then completion of data collection, analysis, and reporting. Clinical sites will be in Massachusetts, Texas, and Wisconsin; this application is for trial coordination at Tufts-New England Medical Center (accompanying are 3: for Data Coordinating Center and 2 Core Laboratories). Inclusion of 15,450 patients (excluding AMI Killip class >2) should provide >80% statistical power to detect 25% reductions in primary endpoints (30-day and 1-year mortality) and major secondary endpoints (cardiac arrest or mortality, and HF hospitalization or mortality, and progression of UAP to AMI). A 400-subject cohort assessed for LV function, ventricular arrhythmia markers, and biochemical tests, will provide >80% power for clinically relevant differences between GIK and placebo. If the 30-50% reduction in acute mortality rates in prior GIK trials and reductions in HF are confirmed, this inexpensive treatment could substantially reduce the most common causes of death and hospitalization in the US. (End of abstract.)