Safety and Efficacy of Empagliflozin Main intenance HD (SEED)

Empagliflozin Main Intenance HD (SEED) 的安全性和功效

基本信息

批准号：
10660436
负责人：
David M Charytan
金额：
$ 36.46万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10660436
关键词：
Acute Address Adult Adverse effects Adverse event Age Albumins Attenuated Binding Proteins Biological Blood Pressure Body Water Cardiovascular Diseases Cardiovascular system Cause of Death Cessation of life Chronic Kidney Failure Clinical Clinical Trials Coronary Arteriosclerosis Creatinine clearance measurement Data Dedications Development Diabetes Mellitus Disease Progression Diuresis End stage renal failure Equipoise Event Exclusion Excretory function Feedback Fluid overload Frequencies Functional disorder General Population Genital Genitalia Genitourinary System Infection Glucose Guidelines Heart failure Hemodialysis High Prevalence Hospitalization Hour Hypertension Hypoglycemia Hypotension Incidence Individual Infection Kidney Kidney Diseases Kidney Failure Knowledge Literature Maintenance Mediating Metabolism Morality Morbidity - disease rate Multicenter Studies Nephrology Outcome Patient Care Patient Readmission Patients Performance Pharmaceutical Preparations Phase Physiological Pilot Projects Placebo Control Placebos Population Proteinuria Proximal Kidney Tubules Randomized Renal function Renin-Angiotensin System Reporting Residual state Risk Risk Factors Risk Reduction Safety Sodium Testing Treatment Efficacy United States Urea Urine Weight absorption cardiovascular risk factor clinically relevant design experience functional decline glycemic control heart rate variability hemodynamics high risk high risk population improved inhibitor innovation mortality mortality risk novel therapeutic intervention novel therapeutics pilot trial preservation prevent protein distribution randomized placebo-controlled clinical trial safety testing sex symporter urinary

项目摘要

PROJECT SUMMARY Each year over 124,000 individuals initiate hemodialysis and there are over 490,000 patients receiving maintenance hemodialysis for end-stage kidney disease in the United States. Cardiovascular (CV) disease remains the leading cause of death, while each patient has 1.6 hospitalizations annually and around 34% of patients are readmitted within 30 days. Individuals initiating hemodialysis generally experience further decline in residual kidney function, a potent risk factor for further morbidity and mortality. Despite the massive burden of morbidity and morality, few therapies have been tested, with even fewer proven, to reduce the risk of mortality in this high-risk population. The development of sodium-glucose co-transporter 2 inhibitors (SGLT2i) has heralded a paradigm-shift in nephrology, with dedicated trials in patients with chronic kidney disease (CKD) reporting substantial reductions in the risk of CKD progression, proteinuria, and CV outcomes, including hospitalization for heart failure. Despite initial guidelines suggesting avoiding initiation of SGLT2i in individuals with moderate or severe CKD, in whom the glucose-lowering effects are attenuated, multiple trials, as well as our own analyses, demonstrate that the effects on glycemic control only mediate a small portion of the overall clinical benefits. Furthermore, SGLT2i provide potent kidney and CV risk reduction compared with placebo even in the absence of diabetes, while they are safe and effectively prevent morbidity and mortality in patients with advanced CKD. However, the safety and efficacy of these therapies have yet to be tested in end stage kidney disease patients requiring initiation of hemodialysis. We therefore propose a phase II, randomized, placebo-controlled, parallel group pilot clinical trial to test the safety and efficacy of empagliflozin among adult patients initiating hemodialysis. The results of our study will inform the design and development of a larger multi-center outcomes trial, which is urgently needed to address the unacceptably high rates of CV disease and associated mortality in this population. Our proposals are clinically relevant, feasible, innovative, and are supported by robust literature in non-hemodialysis patients with CKD. Building on the underlying pathophysiology, the clinical unmet need, and our collective experience in performance of clinical trials, our proposals have the potential to inform and improve the care of patients requiring initiation of HD globally.

项目概要每年有超过 124,000 人开始血液透析，并且有超过 490,000 名患者接受血液透析在美国，维持性血液透析治疗终末期肾病。心血管 (CV) 疾病仍然是死亡的主要原因，而每个患者每年住院治疗 1.6 次，约 34% 患者在 30 天内重新入院。开始血液透析的个体通常会经历进一步的下降残余肾功能是进一步发病和死亡的潜在危险因素。尽管背负着巨大的负担发病率和道德方面，很少有疗法经过测试，被证明可以降低死亡风险的疗法更少在这个高危人群中。钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 的开发预示着范式转变肾脏病学，针对慢性肾病 (CKD) 患者的专门试验报告显着减少 CKD 进展、蛋白尿和心血管结局（包括因心力衰竭住院）的风险。尽管初步指南建议避免在中度或重度 CKD 个体中启动 SGLT2i，其中降血糖作用减弱，多项试验以及我们自己的分析表明，对血糖控制的影响仅介导总体临床益处的一小部分。此外，SGLT2i 即使在没有糖尿病的情况下，与安慰剂相比，也能有效降低肾脏和心血管风险，同时安全有效地预防晚期 CKD 患者的发病率和死亡率。然而，安全和这些疗法的疗效尚未在需要开始治疗的终末期肾病患者中进行测试血液透析。因此，我们提出一项 II 期、随机、安慰剂对照、平行组试点临床试验来测试恩格列净在开始血液透析的成年患者中的安全性和有效性。我们的研究结果将为更大的多中心结果试验的设计和开发提供信息，这是迫切需要解决的问题该人群的心血管疾病发病率和相关死亡率高得令人难以接受。我们的建议是临床相关、可行、创新，并得到非血液透析患者的可靠文献支持慢性肾病。以潜在的病理生理学、临床未满足的需求以及我们的集体经验为基础临床试验的表现，我们的建议有可能为需要的患者提供信息并改善其护理全球范围内启动HD。