THE INORGANIC NITRATE FOR EXERCISE IN HEART FAILURE (INIX-HF) TRIAL

用于心力衰竭锻炼的无机硝酸盐 (INIX-HF) 试验

• 批准号: 9374210
• 负责人: ANDREW R COGGAN
• 金额: $ 23.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9374210
• 关键词: Activities of Daily Living; Adverse effects; Aerobic; Aerobic Exercise; Affect; Biological Availability; Blood; Cachexia; Cardiac; Chronic; Clinical; Clinical Trials; Cross-Over Studies; Data; Data Collection; Data Coordinating Center; Databases; Disease; Dose; Double-Blind Method; EFRAC; Exercise; Extensor; Failure; Foundations; Functional disorder; Future; Goals; Grant; Heart failure; Hour; Hypotension; Image Analysis; Impairment; Ingestion; Knee; Laboratories; Lead; Manuals; Measurement; Measures; Medical center; Metabolic; Muscle; Muscle Contraction; Muscle function; Myocardium; Nitrates; Nitric Oxide; Nitrites; Outcome; Oxygen Consumption; Pathway interactions; Patients; Performance; Pharmacological Treatment; Pharmacology; Pharmacy facility; Phase II Clinical Trials; Physicians; Pilot Projects; Placebo Control; Placebos; Plasma; Procedures; Production; Protocols documentation; Pump; Quality of life; Randomized; Randomized Clinical Trials; Research Design; Research Infrastructure; Route; Site; Skeletal Muscle; Specific qualifier value; Speed; Standardization; Sum; Testing; Time; Torque; Treatment Failure; Work; Writing; alternative treatment; arm; design; disability; effective therapy; exercise capacity; follow-up; hemodynamics; improved; member; mortality; novel; novel therapeutics; operation; outcome forecast; power analysis; quadriceps muscle; response; skeletal abnormality; targeted agent; treadmill

ABSTRACT Heart failure with reduced ejection fraction (HFrEF) affects roughly 3 million in the U.S. and is a mortal and morbid disease. HFrEF impairs a patient's ability to exercise and perform activities of daily living. Although weak cardiac pumping ability clearly contributes to chronic disability associated with HFrEF, abnormal skeletal muscle in patients with HFrEF is also a key debilitating factor. Skeletal muscle is therefore a vital target for treatment of HFrEF. Inorganic nitrate enhances aerobic exercise capacity and muscle power in preliminary studies of patients with HFrEF. The overarching aim of our study (and the follow-up randomized clinical trial [RCT]) is to determine whether inorganic nitrate offers a new, safe and effective treatment for ameliorating the disability due to HFrEF. The Specific Aims of this study are 1) to determine the best dose of inorganic nitrate for patients with HFrEF; 2) to determine the best primary endpoint (aerobic capacity or muscle power) and the number of patients that will be needed for the RCT; and 3) to set up the infrastructure and manuals needed for standardized performance of the RCT protocols across multiple medical centers. For Aim 1, the effects of 10mmol and 20mmol of KNO3 vs. placebo on hemodynamics, and blood levels of nitrate and nitrite and breath NO will be measured and any side effects noted. In Aim 2, a small, phase II clinical trial of 2 wk of KNO3 treatment (dose determined by Aim 1) in a randomized, placebo-controlled, non-crossover design study will be performed. The endpoints of this aim will be aerobic capacity (peak oxygen consumption – VO2peak), measured during treadmill exercise using a metabolic cart and peak quadriceps muscle power measured using a Biodex machine. In Aim 3, all of the infrastructure needed for the RCT will be constructed. A RedCAP™ database for data entry, storage, and export from all RCT sites will be created. All Cores (Data Coordinating Center, Imaging Analysis Core, Laboratory Core, Exercise Analysis Core, Pharmacy Core) for the RCT will be established and Manuals of Operation will be written. The potential impact of finding a new, safe and effective treatment that helps millions of patients beat the disability of HFrEF is enormous.

摘要 心力衰竭伴射血分数降低(HFrEF)在美国影响大约300万人，是一种致命和 病态的疾病。HFrEF损害患者的运动能力和日常生活活动能力。虽然 心脏泵血能力弱明显导致与HFrEF相关的慢性残疾，即骨骼异常 HFrEF患者的肌肉也是一个关键的衰弱因素。因此，骨骼肌是一个重要的目标 HFrEF的治疗。无机硝酸盐初步提高有氧运动能力和肌肉力量 HFrEF患者的研究。我们研究的总体目标(以及后续的随机临床试验 [RCT])的目的是确定无机硝酸盐是否提供了一种新的、安全有效的治疗方法来改善 由于HFrEF造成的残疾。本研究的具体目的是：1)确定无机硝酸盐的最佳用量 对于HFrEF患者；2)确定最佳主要终点(有氧能力或肌肉力量)和 RCT将需要的患者数量；以及3)设置基础设施和所需手册 跨多个医疗中心的RCT协议的标准化性能。对于目标1， 10 mmo3和20 mmo3硝酸钾与安慰剂比较对血流动力学、血液硝酸盐和亚硝酸盐水平及呼吸的影响 将对NO进行测量，并记录任何副作用。在目标2中，对2wk硝酸钾进行了一项小型II期临床试验 在一项随机、安慰剂对照、非交叉设计研究中，治疗(剂量由Aim 1确定)将是 已执行。这一目标的终点将是有氧能力(峰值耗氧量-VO2峰值)， 在跑步机运动中使用代谢车测量，并使用 一台生物索引机。在目标3中，将建造区域工作队所需的所有基础设施。红帽™ 将创建用于从所有RCT站点输入、存储和导出数据的数据库。所有核心(数据协调 中心、影像分析核心、实验室核心、运动分析核心、药房核心)将用于RCT 将编写已建立的操作手册和手册。寻找一种新的、安全有效的 帮助数百万患者战胜HFrEF残疾的治疗是巨大的。