GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment (CCC)

描述（由申请人提供）： 心力衰竭（HF）是美国的一个主要公共卫生问题。虽然药物治疗可以改善结果，但数据表明，已证实的治疗方法仍然没有得到充分利用。目前的指南建议，治疗应滴定到临床试验中使用的目标剂量，但“临床惰性”往往代表了对提供者和患者进行积极的药物治疗滴定的障碍。迫切需要制定策略，以提高慢性HF已证实疗法的利用率，从而改善结局。利钠肽是血流动力学应激的生物标志物，可提供重要的心力衰竭预后信息。利钠肽水平随时间的变化与结局密切相关，HF治疗被证明具有有益效果，可随时间降低利钠肽水平。这些数据表明，利钠肽的连续测量可以作为HF生物标志物指导治疗中药物治疗滴定的指导。“尽管小型研究荟萃分析表明这种方法可以降低死亡率，但仍然需要一项强有力的研究来确定生物标志物指导的治疗是否可以改善慢性HF的结局。我们建议通过使用生物标志物强化治疗指导循证治疗（GUIDE-IT）研究来解决这一未满足的需求，这是一项在HF中进行生物标志物指导治疗的随机临床试验。GUIDE-IT的主要目的是在1100例高风险HF患者中比较药物治疗（滴定至钠尿肽目标）策略与常规治疗。我们的主要假设是，在至少12个月的随访期内，与常规治疗相比，生物标志物指导的治疗将使至心血管死亡或首次HF住院时间的复合终点缩短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学-生活质量核心实验室。GUIDE-IT将测试HF管理的创新模式-根据生理目标进行药物治疗的个体化滴定，而不是“一刀切”的方法。GUIDE-IT的结果将改变指南，并对数百万美国慢性HF患者的管理产生直接的临床意义。

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.