LV Function Assessment Core Lab for IMMEDIATE Trial

母公司的申请是为了支持IMDIATE(在急救护理的初始评估和治疗期间立即加强心肌代谢)试验，这是一项全国性的随机对照临床试验，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，在急性冠脉综合征患者中尽早给予GIK治疗将降低短期(30天)和长期(1年)死亡率。直接审判还假设 早期使用GIK将减少危及生命的室性心律失常的发生率，并通过减轻急性心肌梗死的梗塞范围，有助于保护左心功能，从而降低心力衰竭的倾向。 直接试验研究人群中的一个子样本将包括“生物机制队列”，这些受试者将在最初研究登记后30天返回区域中心，以评估梗死面积、左心功能和脑利钠肽水平。这项应用描述了将支持这一努力的核心实验室操作，并将产生用于检验假设H9的数据：在生物机制样本中，立即使用GIK将与反映30天内发生HF的倾向较低的生理指标相关联，包括a)通过Sestamibi灌注成像缩小梗塞范围；b)通过门控SPECT成像更好地保存左心功能；以及c)较低的脑钠素(BNP)水平。因此，这一核心实验室应用程序的具体目标是：1)建立和支持所需的研究基础设施，以便在区域中心生成关于梗塞面积和左心功能的信息；以及2)以符合当前管理标准的高质量方式对数据进行盲目的中央分析 临床试验中的电子数据。梗塞面积将通过使用sestarnibi SPECT成像的验证技术来评估，左心功能将通过门控SPECT Sestamibi成像和脑利钠肽水平的测量来评估。完成后，这将是有史以来研究GIK效应潜在机制的最大规模的队列。这些数据将提供足够强大的信息来测试亲本试验假设H9中的概念，并为GIK效应的机制提供实质性的见解。

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.