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代谢心肌支持可减少缺血诱导的心律失常、不稳定型心绞痛I（UAP）向急性心肌梗死（AMI）的进展、MI大小和死亡率。对于ST段抬高型心肌梗死（STEMI），GIK可延长冠脉再灌注获益时间。这些作用应降低急性冠状动脉综合征（ACS：包括AMI和UAP）的短期和长期死亡率以及心力衰竭（HF）的倾向。 这些益处与ACS的早期相关，此时挽救生命的风险和机会都最高。因此，我们提出了IMMEDIATE（急诊初始评估和治疗期间立即心肌代谢增强）试验，这是一项随机安慰剂对照临床试验，在ACS患者中尽早立即GIK：在院前急救医疗服务（EMS）环境中，或对于那些到急诊科（ED）就诊的患者，在艾德到达后立即。与之前和正在进行的GIK试验不同，这将测试GIK用于所有ACS而不仅仅是AMI（或STEMI），以及其在院前EMS和艾德环境中的使用。 我们的主要假设是早期GIK可以降低30天和1年的死亡率。主要的次要假设是，瑞舒吉克将减少院前/院内心脏骤停、不稳定型心绞痛进展为急性心肌梗死，并通过限制心肌梗死的大小，降低心力衰竭的倾向。其他的假说涉及这些效应的机制。该项目将花费5年时间：一年准备和测试操作，28个月招募患者，然后完成数据收集，分析和报告。临床研究中心将位于马萨诸塞州、德克萨斯州和威斯康星州;本申请用于塔夫茨-新英格兰医学中心的试验协调（附带3个：数据协调中心和2个核心实验室）。纳入15，450例患者（不包括AMI Killip分级>2）应提供>80%的统计功效，以检测主要终点（30天和1年死亡率）和主要次要终点（心脏骤停或死亡率，HF住院或死亡率，以及UAP进展为AMI）降低25%。评估LV功能、室性心律失常标志物和生化测试的400名受试者队列将为GIK和安慰剂之间的临床相关差异提供>80%的功效。如果证实既往GIK试验中急性死亡率降低30-50%和HF减少，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。 (End抽象）。

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.)