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.

对比剂相关急性肾损伤 (CA-AKI) 是静脉注射碘化物的常见并发症 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) 治疗冠状动脉疾病 (CAD) 和心力衰竭 (HF) 患者估计有 3800 万人。 全世界最常因 CAD 而患心力衰竭，而 CAD 是世界上所有成年人的头号杀手 据估计，美国老年人口（包括退伍军人）的预期增长将与 尽管 PCI 治疗，每年诊断为 HF 的患者人数显着增加（在美国为 50%）。 恢复心力衰竭患者的心脏血流并改善心肌功能，对比 手术中使用的介质可能导致 CA-AKI，可能是由造影剂诱导介导的 肾血管收缩和自由基介导的直接肾小管毒性。 据估计，接受冠状动脉手术的患者 CA-AKI 的发生率在 10% 至 50% 之间 左心室射血分数降低的心力衰竭患者血管造影和 PCI 的发生率较高 (LVEF) 在美国，每年进行大约 140 万例冠状动脉造影手术。 仅在美国退伍军人中，每年就进行大约 30,000 次冠状动脉造影，并且 据估计，超过 100 万次对比增强成像研究是出于各种其他目的。 随着造影剂使用的增加，预计在未来几十年内将呈指数级增长。 CA-AKI 的患病率预计也会上升，CA-AKI 预示着心脏病发作的风险升高，住院时间更长。 住院时间长、住院过程复杂、住院死亡率高。 等渗盐水静脉输液 (IVF) 的施用已成为预防 CA-的标准干预措施 不幸的是，AKI、LVEF 降低的 HF 患者可能无法耐受 IVF。 评估预防性 IVF 和其他药物排除了 HF 患者。目前，没有其他选择。 对患有充血性心力衰竭且 LVEF 降低但无法进行 CA-AKI 治疗的患者进行预防性治疗 这项研究提出了通过应用一种或多种药物引发的远程缺血预处理（RIPC）。 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 肾缺血性损伤和肾小管毒性是最常见的。 CA-AKI 常见的病理生理学概念，按理说 RIPC 可能通过以下途径预防 CA-AKI： 亚硝酸盐诱导的血管舒张和损伤与分子蛋白介导的肾细胞保护相关。 心脏病发作患者数据初步分析 RIPC 与较低 CA-AKI 发生率的关系 在 LVEF 降低的 HF 亚组中，观察到 RIPC 与院内死亡率相关。 CA-AKI、心力衰竭症状的发生率较低，血浆脑钠肽 (BNP) 水平较低。 综上所述，这些观察数据表明 RIPC 在肾脏保护和改善肾功能方面发挥着作用。 可能无法耐受标准治疗（等渗盐水 IVF）的患者群体出现心力衰竭症状。 因此，本研究旨在填补以下人群预防 CA-AKI 的关键空白： 患有充血性心力衰竭的退伍军人正在接受冠状动脉造影和/或 PCI 挽救生命。 提出一项随机临床试验 (RCT) 以确定 RIPC 对 CA-AKI 的影响（主要结果）， 并表征 RIPC 对 BNP 的影响，通过 6 分钟步行测试确定功能能力 距离和 90 天时的主要肾脏不良事件（MAKE-90，次要结果） 充血性 HF 和 LVEF <50% 接受冠状动脉造影和/或 PCI。 确定 RIPC 对患有 HF、LVEF 降低且不能耐受 IVF 的退伍军人的 CA-AKI 的影响。 这项研究的结果将为更大的多中心随机对照试验的设计提供信息，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 AKI 和 HF 的新疗法。