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.

抽象的在美国的射血分数降低（HFREF）的心力衰竭影响约300万，是致命的，是凡人病态疾病。 HFREF会损害患者运动和执行日常生活的能力。虽然弱心脏抽水能力显然有助于与HFREF相关的慢性残疾，异常骨骼 HFREF患者的肌肉也是一个关键的衰弱因素。因此，骨骼肌是 HFREF的处理。初步的无机硝酸盐增强有氧运动能力和肌肉力量 HFREF患者的研究。我们研究的总体目的（以及随访随机临床试验 [RCT]）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，以改善由于HFREF而导致的残疾。这项研究的具体目的是1）确定最佳剂量的无机硝酸盐 HFREF患者； 2）确定最佳的主要终点（有氧能力或肌肉力量）和 RCT需要的患者数量； 3）设置所需的基础架构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， 10mmol和20mmol的KNO3与安慰剂在血液动力学上，硝酸盐和亚硝酸盐和呼吸的血液水平否将测量并注意到任何副作用。在AIM 2中，一项小型II期KNO3的II期临床试验在随机的，安慰剂对照的非交叉设计研究中的治疗（通过目标确定）将是执行。该目标的终点将是有氧能力（峰值消耗量 - vo2peak），使用代谢推车和峰股四头肌肌肉力量在跑步机运动中测量 Biodex机器。在AIM 3中，将构建RCT所需的所有基础架构。 RedCap™ 将创建用于数据输入，存储和从所有RCT站点导出的数据库。所有内核（数据协调中心，成像分析核心，实验室核心，运动分析核心，药房核心）将为RCT 将编写建立和手册的手册。寻找新的，安全有效的潜在影响有助于数百万患者击败HFREF残疾的治疗是巨大的。