Safety and Efficacy of Empagliflozin Main intenance HD (SEED)

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

• 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
• 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

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.

项目摘要 每年超过124,000个人发起血液透析，有490,000多名患者接受 美国维持血液透析用于美国的末期肾脏疾病。心血管疾病 仍然是死亡的主要原因，而每位患者每年有1.6个住院治疗，约占34％ 患者在30天内被重新入院。发起血液透析的人通常会进一步下降 残留肾功能，是进一步发病和死亡率的有效风险因素。尽管负担很大 发病率和道德，几乎没有对疗法进行的疗法，甚至较少，以降低死亡率的风险 在这个高危人群中。 钠 - 葡萄糖共转运蛋白2抑制剂（SGLT2I）的发展已预示 肾脏病，对慢性肾脏疾病（CKD）的专用试验报告了大量降低 出于CKD进展的风险，蛋白尿和CV结果，包括心力衰竭住院。尽管 最初的指南表明避免在患有中度或重度的个体中启动SGLT2I，其中 减少葡萄糖的效果被减弱，多次试验以及我们自己的分析表明， 对血糖控制的影响仅介导一小部分总体临床益处。此外，sglt2i 即使在没有糖尿病的情况下，与安慰剂相比，也提供有效的肾脏和简历风险降低， 安全有效地预防晚期CKD患者的发病率和死亡率。但是，安全和 这些疗法的功效尚未在需要启动的末期肾脏疾病患者中进行测试 血液透析。 因此，我们提出了一项II期，随机，安慰剂对照的，平行组的临床试验，以测试 empagliflozin在启动血液透析的成年患者中的安全性和功效。我们的研究结果将 告知更大的多中心结果试验的设计和开发，这迫切需要解决 该人群中CV疾病和相关死亡率的高度高。我们的建议是 临床上相关，可行，创新，并得到了非诊断性透析患者的强大文献的支持 CKD。建立在基础的病理生理学，临床未满足的需求以及我们的集体经验的基础上 临床试验的性能，我们的建议有可能告知和改善需要的患者的护理 全球高清启动。