The ISCHEMIA-CKD Trial-CCC-Lead Application

ISCHEMIA-CKD 试验 CCC 主导应用

• 批准号: 9397556
• 负责人: Sripal Bangalore
• 金额: $ 117.02万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9397556
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Acute myocardial infarction; Address; Adult; Ancillary Study; Angiography; Angioplasty; Awareness; Bypass; Cardiac Catheterization Procedures; Cardiopulmonary Resuscitation; Cardiovascular Diseases; Cardiovascular system; Caring; Catheterization; Cessation of life; Chronic Kidney Failure; Clinical; Comparative Study; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary artery; Diabetes Mellitus; Dialysis procedure; Disease; Drug Evaluation; EFRAC; Effectiveness; Elderly; End stage renal failure; Enrollment; Equipoise; Event; Frequencies; Fright; General Population; Glomerular Filtration Rate; Goals; Health; Health Policy; Health Resources; Healthcare Systems; Healthy People 2020; Heart Abnormalities; Heart Arrest; Heart failure; Hospitalization; Image; Incidence; Institute of Medicine (U.S.); Intention; International; Investigation; Ischemia; Lead; Life Style; Malignant Neoplasms; Medical; Morbidity - disease rate; Myocardial Infarction; Myocardial Ischemia; Obesity; Observational Study; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Population; Prevalence; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Renal function; Risk; Stents; Stress; Stroke; Symptoms; Testing; Thallium Myocardial Perfusion Imaging Stress Test; Time; Treatment Failure; United States; Unstable angina; aging population; clinical practice; cohort; comparative effectiveness; cost; cost effectiveness; disorder risk; effectiveness research; high risk; high risk population; improved; improved outcome; individual patient; mortality; optimal treatments; outcome forecast; percutaneous coronary intervention; prevent; primary endpoint; prospective; public health relevance; routine care; treatment strategy; trial comparing

DESCRIPTION (provided by applicant): PROJECT SUMMARY/ABSTRACT The objective of the proposed trial, International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease (ISCHEMIA-CKD) Ancillary Study, is to determine the best management strategy for stable ischemic heart disease (SIHD) patients with advanced chronic kidney disease (CKD) [defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2) or on dialysis] and moderate-severe ischemia. ISCHEMIA-CKD will be a prospective, multicenter, international, randomized, controlled trial, conducted as a trial within the main ISCHEMIA trial that will enroll 1,000 SIHD patients with advanced CKD with moderate-severe ischemia by stress imaging and ejection fraction e35%. The trial hypothesis is that for patients with moderate-severe ischemia on stress imaging, a routine invasive strategy (INV) with cardiac catheterization (cath) followed by revascularization plus optimal medical therapy (OMT) is superior to a conservative strategy (CON) of OMT, with cath and revascularization reserved for patients who fail OMT. The primary endpoint will be time to death from any cause or myocardial infarction (MI). Quality of life and cost-effectiveness will also be compared between the two strategies. Patients with CKD are more likely to die than reach end stage renal disease (ESRD) and are therefore considered coronary artery disease (CAD) risk equivalents. The prognosis of patients with advanced CKD is poor with a mortality rate as high as 50-70% at 4-years and is worse than that for patients who have cancers, heart failure, stroke or acute MI. Despite this high risk of death, ~80% of recent CAD trials exclude CKD subjects and most of the treatments aimed at reducing their events are therefore extrapolated from cohorts without CKD. Advanced CKD subjects are underrepresented in contemporary trials comparing revascularization with medical therapy in SIHD patients such as the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, or the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, making any assessment about the utility of revascularization plus medical therapy vs. initial medical therapy alone in ths cohort problematic. Limited observational studies have suggested a possible survival benefit of revascularization but yet it is rarely (10-45%) performed for fear of acute complications including contrast induced acute kidney injury, indicating substantial equipoise in current clinical practice As we prepare for the CKD boom with an aging population and increasing prevalence of diabetes and obesity, and if one of the major goals as set by Healthy People 2020 (improving survival and quality of life for people with CKD) is to be accomplished, a treatment strategy trial such as the ISCHEMIA- CKD trial is urgently needed to target a reduction in death and cardiovascular events in this high-risk population. The importance of this question to be addressed by ISCHEMIA-CKD is the reason it was ranked by the Institute of Medicine among the top 100 US priorities for comparative effectiveness research.

描述（由申请人提供）： 项目摘要/摘要 拟议试验的目的，即药物和侵入性方法的健康有效性比较国际研究 - 慢性肾病 (ISCHEMIA-CKD) 辅助研究，是确定患有晚期慢性肾病 (CKD) 的稳定型缺血性心脏病 (SIHD) 患者的最佳治疗策略 [定义为估计肾小球滤过率 (eGFR) <30 mL/min/1.73m2）或透析]和中重度缺血。 ISCHEMIA-CKD 将是一项前瞻性、多中心、国际、随机、对照试验，作为主要 ISCHEMIA 试验中的一项试验进行，该试验将招募 1,000 名患有晚期 CKD 的 SIHD 患者，通过应力成像和射血分数 e35% 发现中重度缺血。试验假设是，对于应力成像中重度缺血的患者，常规侵入性策略（INV）加心导管插入术（cath）然后血运重建加最佳药物治疗（OMT）优于OMT保守策略（CON），即为OMT失败的患者保留导管和血运重建。主要终点是全因死亡或心肌梗死 (MI) 的时间。还将比较两种策略之间的生活质量和成本效益。 CKD 患者比达到终末期肾病 (ESRD) 的患者更有可能死亡，因此被视为冠状动脉疾病 (CAD) 的风险相当者。晚期CKD患者的预后较差，4年死亡率高达50-70%，比癌症、心力衰竭、中风或急性心肌梗死患者的预后更差。尽管死亡风险很高，但最近约 80% 的 CAD 试验排除了 CKD 受试者，因此大多数旨在减少其事件的治疗都是从无 CKD 的队列中推断出来的。在比较 SIHD 患者血运重建与药物治疗的当代试验中，晚期 CKD 受试者的代表性不足，例如旁路血管成形术血运重建调查 2 糖尿病 (BARI 2D) 试验或利用血运重建和积极药物评估的临床结果 (COURAGE) 试验，对血运重建加药物治疗与单独初始药物治疗的效用进行评估 队列有问题。有限的观察性研究表明血运重建可能对生存有好处，但由于担心出现急性并发症，很少（10-45%）进行，包括 对比剂诱导的急性肾损伤，表明当前临床实践中的基本平衡当我们为人口老龄化以及糖尿病和肥胖症患病率上升的 CKD 热潮做准备时，如果要实现《健康人 2020》设定的主要目标之一（提高 CKD 患者的生存率和生活质量），治疗策略试验 迫切需要诸如 ISCHEMIA-CKD 试验之类的试验来减少这一高危人群的死亡和心血管事件。 ISCHEMIA-CKD 解决的这个问题非常重要，因此它被医学研究所列为美国比较有效性研究的 100 项优先事项之一。