Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (EQOL)

使用生物标志物强化治疗 (EQOL) 指导循证治疗

• 批准号: 8235545
• 负责人: Daniel B Mark
• 金额: $ 14.61万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-08 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8235545
• 关键词: Address; American; Biological Markers; Cardiovascular system; Cessation of life; Chronic; Clinical; Clinical Trials; Companions; Congestive Heart Failure; Data; Data Coordinating Center; Dose; EFRAC; Economics; Goals; Guidelines; Heart failure; Hospitalization; Intention; Life; Living Costs; Measurement; Medical; Meta-Analysis; Modeling; Multicenter Trials; NT-proBNP; Natriuretic Peptides; Outcome; Patients; Physiological; Provider; Public Health; Quality of life; Quality-Adjusted Life Years; Randomized; Randomized Clinical Trials; Relative (related person); Review Committee; Stress; Symptoms; Testing; Time; Titrations; United States; abstracting; arm; base; cost; cost effective; cost effectiveness; evidence base; evidence based guidelines; follow-up; health related quality of life; hemodynamics; high risk; improved; innovation; mortality; prognostic; prospective; treatment as usual; treatment strategy

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. PUBLIC HEALTH RELEVANCE: The GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) Study is a clinical trial testing adjustment of heart failure (HF) therapy based on natriuretic peptides vs. usual care in high risk patients with HF. GUIDE-IT will test an innovative model of HF management using the individualized titration of therapy to a biologic target, which will have immediate clinical implications for millions of patients with HF. (End of Abstract)

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。尽管药物治疗可以改善结果，但数据表明，经过验证的疗法仍未得到充分利用。目前的指南建议，治疗应向临床试验中使用的目标剂量逐步调整，但“临床惯性”往往对提供者和患者来说都是积极调整药物治疗的障碍。迫切需要制定策略来提高慢性心力衰竭的成熟疗法的利用率，以改善结果。利钠肽是血流动力学应激的生物标志物，可为心力衰竭提供重要的预后信息。随着时间的推移，利尿钠肽水平的变化与结果密切相关，并且经证明，心力衰竭疗法具有有益的效果，随着时间的推移，利尿钠肽水平会降低。这些数据表明，钠尿肽的连续测量可以作为心力衰竭药物治疗滴定的指导——“生物标志物引导治疗”。尽管小型研究荟萃分析表明这种方法可以降低死亡率，但仍然需要进行强有力的研究来确定生物标志物引导治疗是否可以改善慢性心力衰竭的预后。我们建议通过使用生物标志物强化治疗的 GUIDing 循证治疗 (GUIDE-IT) 研究来解决这一未满足的需求，这是一项针对心力衰竭的生物标志物指导治疗的随机临床试验。 GUIDE-IT 的主要目的是比较 1100 名心力衰竭高危患者的以利尿钠肽为靶点滴定药物治疗策略与常规护理。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，生物标志物引导治疗将导致心血管死亡或首次心力衰竭住院时间的复合终点缩短 20%。该应用程序包括临床协调中心、数据协调中心和经济-生活质量核心实验室。 GUIDE-IT 将测试心力衰竭管理的创新模式，即针对生理目标的个性化药物治疗滴定，而不是“一刀切”的方法。 GUIDE-IT 的结果将改变指南，并对数百万患有慢性心力衰竭的美国人的管理产生直接的临床影响。 公共卫生相关性： GUIDing 使用生物标志物强化治疗的循证治疗 (GUIDE-IT) 研究是一项临床试验，测试对基于利钠肽的心力衰竭 (HF) 治疗与常规治疗的高危心力衰竭患者进行调整。 GUIDE-IT 将测试一种创新的心力衰竭管理模式，使用针对生物目标的个体化滴定疗法，这将对数百万心力衰竭患者产生直接的临床影响。 （摘要完）