LV Function Assessment Core Lab for IMMEDIATE Trial

母申请是为了支持IMMEDIATE（急诊初始评估和治疗期间的立即心肌代谢增强）试验，这是一项国家随机对照临床试验，旨在测试静脉注射葡萄糖、胰岛素和钾（GIK）对急性冠状动脉综合征的影响。据推测，与常规治疗相比，在急性冠脉综合征中尽早给予GIK将降低短期（30天）和长期（1年）死亡率。即时试验还假设， 早期使用GIK将降低危及生命的室性心律失常的发生率，并且通过减轻AMI中的梗塞面积，将有助于保持左心室功能，从而降低心力衰竭的倾向。 IMMEDIATE试验研究人群的子样本将组成“生物机制队列”，这些受试者将在首次研究入组后30天返回区域中心，以评价梗死面积、左心室功能和脑钠肽水平。本申请描述了将支持这一努力的核心实验室操作，并将生成用于检验假设H9的数据：“在生物机制样本中，立即使用GIK将与反映30天时HF倾向较低的生理指标相关，包括a）通过sestamibi灌注成像显示梗死面积较小; B）通过门控SPECT成像显示LV功能保留较好;和c）降低脑利钠肽（BNP）水平。“因此，该核心实验室应用程序的具体目的是：1）建立和支持在区域中心生成梗死面积和左心室功能信息所需的研究基础设施，2）以符合当前监管处理标准的高质量方式对数据进行盲态中心分析。 临床试验中的电子数据。将使用sestarnibi SPECT成像通过经验证的技术评估左室大小，并将通过门控SPECT sestamibi成像和脑钠肽水平测量评估左室功能。完成后，这将是有史以来研究GIK效应潜在机制的最大队列。这些数据将提供具有足够功效的稳健信息，以检验母试验假设H9中的概念，并为GIK效应的机制提供实质性见解。

The parent application is for support of the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care) Trial, a national randomized controlled clinical trial to test the impact of intravenous glucose, insulin, and potassium (GIK), for acute coronary syndromes. It is hypothesized that GIK, administered as early as possible in acute coronary syndromes, will reduce short-term (30- day) and long-term (1-year) mortality compared to usual treatment. The IMMEDIATE Trial also hypothesizes that the early use of GIK will reduce the incidence of life-threatening ventricular arrhythmias, and by mitigating infarct size in AMI, will help preserve left ventricular function and will thereby reduce the propensity for heart failure. A subsample of the IMMEDIATE Trial study population will comprise the "biologic mechanism cohort", and these subjects will return to the regional centers at 30 days after initial study enrollment for evaluation of infarct size, left ventricular function, and brain natriuretic peptide level. This application describes the core laboratory operations that will support this effort, and will generate the data used to test hypothesis H9: "In the biological mechanism sample, immediate GIK use will be associated with physiologic indicators reflecting a lower propensity for HF at 30 days including a) smaller infarct size by sestamibi perfusion imaging; b) better preserved LV function by gated SPECT imaging; and c) lower brain natriuretic peptide (BNP) levels." Thus the Specific Aims of this core laboratory application are: 1) to set up and support the study infrastructure required to generate information on infarct size and left ventricular function at the regional centers, and 2) to perform the blinded central analyses of the data in a high-quality manner consistent with current regulatory standards of handling electronic data in clinical trials. Infarct size will be assessed by a validated technique using sestarnibi SPECT imaging, and left ventricular function will be assessed by gated SPECT sestamibi imaging and measurements of brain natriuretic peptide levels. When completed, this will be the largest cohort ever studied examining the potential mechanisms of GIK effect. These data Will provide robust information with sufficient power to test the concepts in Hypothesis H9 of the parent trial and provide substantial insights into the mechanism of GIK effect.