GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment (DCC)

描述(由申请人提供)： 心力衰竭(HF)在美国是一个主要的公共卫生问题。尽管药物治疗可以改善结果，但数据表明，经过验证的治疗方法仍然没有得到充分利用。目前的指导方针建议，治疗应按临床试验中使用的目标剂量进行滴定，但对于提供者和患者来说，“临床惰性”往往是积极滴定医疗方案的障碍。迫切需要制定战略，以改进对慢性心力衰竭的已证实疗法的利用，以改善结果。利钠肽是血流动力学应激的生物标志物，可为心力衰竭的预后提供重要信息。随着时间的推移，利钠肽水平的变化与结果密切相关，而HF治疗被证明具有有益的效果，随着时间的推移，结果会降低利钠肽水平。这些数据表明，利钠肽的系列测量可作为心力衰竭“生物标记物引导治疗”中药物治疗滴定的指南。尽管小规模研究荟萃分析表明这种方法可以降低死亡率，但仍需要一项强有力的研究来确定生物标记物引导的治疗是否能改善慢性心力衰竭的预后。我们建议通过生物标记物强化治疗的指导性循证治疗(GUIDE-IT)研究来解决这一未得到满足的需求，这是一项生物标记物导向治疗心力衰竭的随机临床试验。GUIDE-IT的主要目的是比较1100名心力衰竭高危患者中以利钠肽为靶点的药物治疗策略与常规治疗策略。我们的主要假设是，在至少12个月的随访期内，生物标记物引导治疗将使心血管死亡或首次入院治疗的综合终点时间比常规治疗减少20%。该应用程序包括一个临床协调中心、一个数据协调中心和一个经济-生活质量核心实验室。GUIDE-IT将测试一种创新的HF管理模式--对生理目标进行个性化的药物治疗滴定，而不是“一刀切”的方法。GUIDE-IT的结果将是指南的改变，并对数百万患有慢性心力衰竭的美国人的管理具有直接的临床意义。

DESCRIPTION (provided by applicant): Heart failure (HF) is a major public health problem in the United States. Although medical therapy can improve outcomes, data suggest that proven therapies continue to be underutilized. Current guidelines suggest that treatment be titrated toward the target doses used in clinical trials, but "clinical inertia" often represents a barrier to aggressive titration of medical therap for both providers and patients. There is a pressing need to develop strategies to improve the utilization of proven therapies for chronic HF in order to improve outcomes. The natriuretic peptides are biomarkers of hemodynamic stress that provide important prognostic information in HF. Changes in natriuretic peptide levels over time are strongly associated with outcomes, and HF therapies proven to have beneficial effects outcomes decrease natriuretic peptide levels over time. These data suggest that serial measurements of natriuretic peptides may serve as a guide to the titration of medical therapy in HF - "biomarker guided therapy." Although small studies meta-analyses have suggested a decrease in mortality with this approach, there remains an unmet need for a robustly powered study to determine whether biomarker guided therapy improves outcomes in chronic HF. We propose to address this unmet need with the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) Study, a randomized clinical trial of biomarker guided therapy in HF. The primary aim of GUIDE-IT is to compare a strategy of medical therapy titrated to a natriuretic peptide target to usual care in 1100 high risk patients with HF. Our primary hypothesis is that biomarker guided therapy will reduce the composite endpoint of time to cardiovascular death or first HF hospitalization by 20% compared to usual care over a follow up period of at least 12 months. This application includes a Clinical Coordinating Center, a Data Coordinating Center, and an Economics-Quality of Life core lab. GUIDE-IT will test an innovative model of HF management-the individualized titration of medical therapy to a physiologic target rather than a "one size fits all" approach. Results of GUIDE-IT will be guideline changing and have immediate clinical implications for the management of millions of Americans living with chronic HF.