Remote ischemic preconditioning for renal and cardiac protection in congestive heart failure (RICH) trial

充血性心力衰竭 (RICH) 试验中远程缺血预处理对肾脏和心脏的保护

• 批准号: 10426064
• 负责人: Oladipupo Olafiranye
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426064
• 关键词: Activities of Daily Living; Acute Renal Failure with Renal Papillary Necrosis; Adult; Alternative Therapies; Angiography; Blood Pressure; Blood Vessels; Blood flow; Brain natriuretic peptide; Cardiac; Cell Cycle Arrest; Cessation of life; Clinical Trials; Complication; Congestive Heart Failure; Contrast Media; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Cytoprotection; Data; Data Analyses; Diagnosis; Diagnostic Imaging; Double-Blind Method; Elderly; Epithelial Cells; Event; Exclusion; Exposure to; Free Radicals; Generations; Growth; Heart; Heart Rate; Heart failure; Helicopter; Hospital Mortality; Hospitalization; IV Fluid; Incidence; Intervention; Intravenous; Ischemia; Ischemic Preconditioning; Isotonic Exercise; Kidney; Left Ventricular Ejection Fraction; Length of Stay; Life; Limb structure; Long-Term Effects; Mediating; Molecular; Monitor; Morbidity - disease rate; Multicenter Trials; Myocardial; Myocardial Infarction; Nature; Nitrites; Organ; Outcome; Participant; Patients; Persons; Plasma; Population; Prevalence; Prevention; Preventive therapy; Procedures; Process; Proteins; Randomized Controlled Clinical Trials; Renal Replacement Therapy; Reperfusion Therapy; Research Project Grants; Risk; Role; Safety; Saline; Serum; Subgroup; Symptoms; Testing; Time; Toxic effect; Translations; Tubular formation; United States Department of Veterans Affairs; Vasodilation; Veterans; Walking; clinical practice; contrast enhanced; cooperative study; cost; design; hemodynamics; high risk; imaging study; improved; intravenous administration; ischemic injury; kidney cell; kidney dysfunction; military veteran; mortality; novel therapeutics; patient population; percutaneous coronary intervention; pressure; prevent; primary outcome; programs; prophylactic; randomized, clinical trials; renal ischemia; secondary outcome; vasoconstriction

Contrast-associated acute kidney injury (CA-AKI) is a common complication of intravenous, iodinated contrast media, that is widely used for coronary angiography and percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD) and heart failure (HF). An estimated 38 million people worldwide suffer from HF most frequently as a consequence of CAD, the number one killer of all adults in the US. The expected growth of the elderly population including Veterans is estimated to be paralleled by a significant increase (50% in the US) in the number of patients diagnosed with HF every year. Although PCI restores blood flow to the heart and improves myocardial function in patients with HF, the contrast media used for the procedure can cause CA-AKI, possibly mediated by contrast–induced vasoconstriction of renal blood vessels and free radical–mediated direct renal tubular toxicity. The incidence of CA-AKI is estimated to range between 10 and 50% in patients undergoing coronary angiography and PCI with higher rates in patients with HF with reduced left ventricular ejection fraction (LVEF). In the U.S, approximately 1.4 million coronary angiogram procedures are performed each year. Among the U.S Veterans alone, approximately 30,000 coronary angiograms are performed annually, and over 1 million contrast-enhanced imaging studies are performed for other various purposes. This estimate is expected to increase exponentially in the next few decades. With increasing use of contrast media, the prevalence of CA-AKI is also expected to rise. CA-AKI predicts elevated risk of heart attack, longer hospital stay, more complicated hospitalization course, and higher in-hospital mortality. Although, periprocedural administration of isotonic saline intravenous fluid (IVF) has been the standard intervention to prevent CA- AKI, patients with HF with reduced LVEF may not tolerate IVF. Unfortunately, all the major clinical trials evaluating prophylactic IVF and other agents excluded patients with HF. Currently, there is no alternative preventive therapy for CA-AKI in patients with congestive HF with reduced LVEF who cannot tolerate IVF. This study proposes remote ischemic pre-conditioning (RIPC) elicited by application of one or more, brief episodes of ischemia and reperfusion of a limb, as a promising alternative therapy for preventing or attenuating CA-AKI. Given that renal ischemic injury and tubular toxicity are the most common pathophysiological concepts of CA-AKI, it stands to reason that RIPC may prevent CA-AKI via nitrite-induced vasodilation and damage associated molecular protein -mediated renal cell protection. In the preliminary analysis of data of patients with heart attack, an association of RIPC with lower rate of CA-AKI and in-hospital mortality was observed. In the subgroup with HF with reduced LVEF, RIPC was associated with lower incidence of CA-AKI, HF symptoms and lower level of plasma brain natriuretic peptide (BNP). Taken together, these observational data suggest a role for RIPC in renal protection and improvement in HF symptoms in a population of patients who may not tolerate the standard therapy, isotonic saline IVF. Therefore, this study is intended to fill a critical void in the prevention of CA-AKI in a population of Veterans with congestive HF undergoing life-saving coronary angiography and/or PCI. This study proposes a randomized clinical trial (RCT) to determine the effect of RIPC on CA-AKI (primary outcome), and to characterize the effect of RIPC on BNP, functional capacity determined by 6-minute walk test distance, and major adverse kidney events at 90 days (MAKE-90, secondary outcomes) in patients with congestive HF and LVEF <50% undergoing coronary angiography and/or PCI. This research project will determine the effect of RIPC on CA-AKI in Veterans with HF with reduced LVEF who cannot tolerate IVF. The findings from this study will inform the design of a larger multi-center RCT to determine the long-term effects of RIPC on morbidity/mortality in HF population. It will help develop new therapies for AKI and HF.

造影剂相关急性肾损伤（CA-AKI）是静脉注射碘剂的常见并发症 造影剂，广泛用于冠状动脉造影和经皮冠状动脉介入治疗 (PCI)冠心病（CAD）和心力衰竭（HF）患者。估计有3800万人 在世界范围内，HF最常由CAD引起，CAD是所有成年人的头号杀手， 美方包括退伍军人在内的老年人口的预期增长估计将超过 每年诊断为HF的患者数量显著增加（美国为50%）。虽然PCI 恢复心脏血流，改善心力衰竭患者的心肌功能， 用于手术的介质可引起CA-AKI，可能由造影剂诱导的 肾血管收缩和自由基介导的直接肾小管毒性。的 在接受冠状动脉造影的患者中，CA-AKI的发生率估计在10%至50%之间。 左室射血分数降低的HF患者的血管造影和PCI发生率较高 （LVEF）。在美国，每年进行大约140万次冠状动脉造影手术。 仅在美国退伍军人中，每年就进行约30，000次冠状动脉造影， 为其他各种目的进行了超过100万次对比增强成像研究。这一估计 预计在未来几十年内将呈指数级增长。随着造影剂使用的增加， 预计CA-AKI的患病率也将上升。CA-AKI预测心脏病发作风险升高，住院时间更长 住院时间长、住院过程复杂、住院死亡率高。虽然，围手术期 给予等渗盐水静脉内流体（IVF）一直是预防CA的标准干预。 阿基、LVEF降低的HF患者可能无法耐受IVF。不幸的是，所有主要的临床试验 评估预防性IVF和其他药物排除HF患者。目前，没有其他选择 在无法接受CA-AKI预防治疗的充血性HF伴LVEF降低患者中进行CA-AKI预防治疗 可以忍受IVF。这项研究提出了远程缺血预处理（RIPC）引起的应用一个或 更多的是，短暂的肢体缺血和再灌注，作为一种有前途的替代疗法， 预防或减轻CA-AKI。考虑到肾缺血性损伤和肾小管毒性是最常见的 由于CA-AKI的常见病理生理学概念，RIPC可以通过以下途径预防CA-AKI，这是理所当然的 亚硝酸盐诱导的血管舒张和损伤相关的分子蛋白介导的肾细胞保护。在 心脏病发作患者数据的初步分析，RIPC与CA-AKI发生率较低的相关性 并观察住院死亡率。在LVEF降低的HF亚组中，RIPC与 CA-AKI、HF症状的发生率较低，血浆脑钠肽（BNP）水平较低。 总之，这些观察数据表明RIPC在肾脏保护和改善肾脏疾病中的作用。 可能不耐受标准治疗（等渗盐水IVF）的患者人群中的HF症状。 因此，本研究旨在填补以下人群中预防CA-AKI的关键空白： 患有充血性HF的退伍军人接受挽救生命的冠状动脉造影和/或PCI。本研究 提出了一项随机临床试验（RCT）来确定RIPC对CA-AKI的影响（主要结局）， 并描述RIPC对BNP的影响，通过6分钟步行试验测定功能容量 患者90天时的主要肾脏不良事件（MAKE-90，次要结局） 充血性HF和LVEF <50%，接受冠状动脉造影和/或PCI。该研究项目将 确定RIPC对不能耐受IVF的HF伴LVEF降低的退伍军人中CA-AKI的影响。 本研究的结果将为更大规模的多中心RCT设计提供信息，以确定长期 RIPC对HF人群发病率/死亡率的影响。它将有助于开发阿基和HF的新疗法。