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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

基本信息

批准号：
9754867
负责人：
ANDREW R COGGAN
金额：
$ 22.93万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9754867
关键词：
Activities of Daily Living Adverse effects Aerobic Aerobic Exercise Affect Biological Availability Blood Cachexia Cardiac Chronic Clinical Clinical Trials Clinical trial protocol document 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 Infrastructure 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 Placebos Plasma Procedures Production Protocols documentation Pump Quality of life Randomized Randomized Clinical Trials Research Design Route Site Skeletal Muscle Specific qualifier value Speed Standardization Sum Testing Time Torque Treatment Failure Work Writing alternative treatment appropriate dose arm design disability effective therapy exercise capacity follow-up hemodynamics improved member mortality novel novel therapeutics operation outcome forecast power analysis primary endpoint quadriceps muscle response side effect skeletal abnormality targeted agent treadmill

项目摘要

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.

抽象的射血分数降低的心力衰竭 (HFrEF) 在美国影响着大约 300 万人，是一种致命的疾病病态的疾病。 HFrEF 损害患者锻炼和进行日常生活活动的能力。虽然心脏泵血能力弱显然会导致与 HFrEF、骨骼异常相关的慢性残疾 HFrEF 患者的肌肉也是一个关键的衰弱因素。因此，骨骼肌是重要的目标 HFrEF 的治疗。无机硝酸盐增强有氧运动能力和初步肌力 HFrEF 患者的研究。我们研究的总体目标（以及后续随机临床试验 [RCT]）旨在确定无机硝酸盐是否提供一种新的、安全且有效的治疗方法来改善 HFrEF 导致的残疾。本研究的具体目标是 1) 确定无机硝酸盐的最佳剂量对于 HFrEF 患者； 2) 确定最佳主要终点（有氧能力或肌肉力量）和 RCT 需要的患者数量； 3) 建立所需的基础设施和手册跨多个医疗中心的 RCT 协议的标准化性能。对于目标 1，效果 10mmol 和 20mmol KNO3 与安慰剂对血流动力学、硝酸盐和亚硝酸盐血液水平以及呼吸的影响将测量 NO 并记录任何副作用。在目标 2 中，一项为期 2 周的 KNO3 小型 II 期临床试验随机、安慰剂对照、非交叉设计研究中的治疗（剂量由目标 1 确定）将执行。该目标的终点是有氧能力（峰值耗氧量 – VO2peak），在跑步机锻炼期间使用代谢车测量，并使用峰值股四头肌力量测量 Biodex 机器。在目标 3 中，将建设 RCT 所需的所有基础设施。红帽™ 将创建用于所有 RCT 站点的数据输入、存储和导出的数据库。所有核心（数据协调 RCT 的中心、影像分析核心、实验室核心、运动分析核心、药学核心）建立并编写操作手册。寻找新的、安全且有效的方法的潜在影响帮助数百万患者战胜 HFrEF 残疾的治疗是巨大的。