Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets): A Pragmatic, Multi-Center, Randomized Controlled Trial

退伍军人透析第一年增量血液透析 (IncHVets)：一项务实、多中心、随机对照试验

• 批准号: 10486289
• 负责人: Kamyar Kalantar-Zadeh
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10486289
• 关键词: Address; Adverse event; American; Ancillary Study; Blood Vessels; Cachexia; Cardiac; Cardiovascular system; Caregiver Burden; Caring; Client satisfaction; Clinic; Clinic Visits; Clinical; Clinical Trials; Costs and Benefits; Dialysis patients; Dialysis procedure; Dose; Eating; Eligibility Determination; Emergency department visit; End stage renal failure; Event; Fatigue; Frequencies; Future; GDF15 gene; Growth; Healthcare Systems; Hemodialysis; Hospitalization; Human Resources; Hypotension; Hypotensives; Impaired health; Inflammation; Inflammatory; Injury to Kidney; Intervention; Kidney; Kidney Diseases; Left; Left Ventricular Mass; Life; Longevity; Maintenance; Malnutrition; Measures; Medical center; Muscle; Nutritional; Nutritional status; Organ; Outcome; Outcome Measure; Outpatients; Output; Parents; Patient Outcomes Assessments; Patients; Physical Function; Physical Performance; Population; Pragmatic clinical trial; Proteins; Protocols documentation; Provider; Randomized, Controlled Trials; Regimen; Renal function; Research Design; Research Personnel; Residual state; Resources; Safety; Schedule; Serum; Site; Symptoms; System; Testing; Time; Time trend; Urea; Urine; Veterans; Veterans Health Administration; Withdrawal; arm; coping; cost; design; experience; frailty; functional status; health care service utilization; health related quality of life; hyperkalemia; improved; indexing; mortality; mortality risk; muscle form; nutrition; physical conditioning; pragmatic study; precision medicine; preference; preservation; primary endpoint; primary outcome; safety assessment; safety outcomes; safety testing; scale up; secondary endpoint; secondary outcome; standard of care; survival prediction; wasting

PROJECT SUMMARY Each year approximately 12,000 Veterans develop end-stage renal disease (ESRD) and initiate dialysis treatment. These patients comprise >10% of the US incident ESRD population. Dialysis is costly and associated with impaired health-related quality of life (HRQOL) and high mortality risk, particularly in the first dialysis year. The current paradigm is to start treatment with full-dose thrice-weekly hemodialysis (HD) irrespective of patients' residual kidney function (RKF), and this abrupt transition increases patients' and care- partners' burden and suffering and may limit their preferences. Furthermore, recent evidence suggests that Veterans who receive dialysis in a VA center have greater survival compared to those treated in non-VA units. Although not currently the standard of care, evidence suggests that a gradual or incremental dialysis transition using an initial twice-weekly HD schedule may confer substantial benefits including more dialysis- free time, longer RKF preservation, vascular access longevity, less intradialytic hypotension and end-organ damage, reduced post-dialysis fatigue, and less patient suffering. Hence, an incremental dialysis transition may result in improved HRQOL through improved physical function, less fatigue, greater energy, and improved patient satisfaction and life participation by mitigating the burden of excessive dialysis in daily life. Pragmatic studies with immediate clinical impact are urgently needed to shift the focus of dialysis from an abrupt thrice-weekly HD start to a safe and effective personalized dialysis regimen. Moreover, implementing a twice-weekly HD schedule would allow 20% more Veterans to receive care within a VA-based dialysis unit. In the spirit of RFA CX-21-006 for clinical trials, in this multiple-PI, multi-site, pragmatic, 1:1 randomized controlled trial (RCT), parallel with Veterans' routine dialysis therapy, we will test the safety and efficacy of an incremental twice-weekly HD protocol, compared to standard-of-care thrice-weekly HD, in Veterans who meet predefined eligibility criteria. We plan to compare twice-weekly (incremental) with thrice-weekly (conventional) HD initiation in 252 Veterans with incident ESRD, who will transition to maintenance HD therapy in six VA centers. Using quarterly assessments for up to 12 months, we will examine the Short Form 36 (SF36) HRQOL physical component score as the primary outcome, as well as Dialysis Symptom Index and SF36 energy/ fatigue score as secondary endpoints. Additional secondary outcomes will include preservation of RKF, dialysis adequacy, nutritional status, and protein-energy wasting markers to be measured quarterly. Safety assessments will include mortality, dialysis withdrawals, emergency room visits, hospitalizations, hyperkalemia, and major adverse cardiovascular events. In a substudy examining exploratory outcomes in 112 Veterans from three VA centers in the parent trial, we will also examine of cardiac measures including left ventricular mass, as well as nutritional/physical function indices of muscle mass and physical performance. Our proposed pragmatic RCT addresses a major unmet need in Veterans with incident ESRD initiating dialysis by focusing on improving HRQOL and preserving RKF, the two strongest predictors of survival and patient satisfaction. The results of this study may enable more Veterans to receive therapy in a VA based dialysis center. Our study may lead to a paradigm shift with immediate impact on kidney care in Veterans and in the broader ESRD population. The pragmatic design will permit a rapid scaling-up of the interventions in larger settings since the RCT takes advantage of resources and personnel that are readily available in VA centers under experienced investigators and clinicians across multiple VA sites nationwide. This proposed study challenges the current standard of care of outright thrice weekly HD in the first year of dialysis therapy, during which patients' suffering and mortality are the highest, and is less likely to be supported by for-profit dialysis providers given the perceived reduction in revenue if twice-weekly HD is to be implemented broadly.

项目摘要 每年约有12,000名退伍军人患终末期肾脏疾病（ESRD）并启动透析 治疗。这些患者占美国事件ESRD人群的10％。透析是昂贵的， 与健康相关的生活质量受损（HRQOL）和高死亡率风险相关，尤其是在第一次 透析年。当前的范式是通过全剂量三次血液透析（HD）开始治疗 不论患者的残留肾功能（RKF），这种突然过渡会增加患者和护理 伴侣的负担和痛苦，可能会限制他们的偏好。此外，最近的证据表明 与非VA单位治疗的退伍军人相比，在VA中心接受透析的退伍军人的生存率更高。 尽管目前不是护理标准，但有证据表明逐渐或增量的透析 使用初始两次高清时间表的过渡可能会带来可观的好处，包括更多透析 空闲时间，较长的RKF保存，血管通道寿命，远程内部低血压和末端器官 损害，减少透析后疲劳以及患者的痛苦减少。因此，透析过渡 通过改善身体功能，疲劳，更大的能量和 通过减轻日常生活中过度透析的负担来提高患者满意度和生活的参与。 迫切需要具有直接临床影响的务实研究，以将透析的重点从 每周三次突然开始进行安全有效的个性化透析方案。此外，实施 每周两次的高清计划将允许20％的退伍军人在基于VA的透析单元中获得护理。 本着RFA CX-21-006的临床试验精神 对照试验（RCT），与退伍军人的常规透析治疗并行，我们将测试 与年龄的三次高清高清相比，每周两次的高清协议在遇见的退伍军人中 预定义的资格标准。我们计划每周两次（增量）与每周三次（常规）进行比较 252名退伍军人的高清启动与事件ESRD发生，他们将过渡到六个VA的维护高清治疗 中心。使用最多12个月的季度评估，我们将检查短表36（SF36）HRQOL 物理成分评分是主要结果，以及透析症状指数和SF36 Energy/ 疲劳得分为次要终点。其他次要结果将包括保存RKF， 透析充足性，营养状况和蛋白质能量浪费标记，每季度测量。安全 评估将包括死亡率，透析提取，急诊就诊，住院治疗， 高钾血症和重大不良心血管事件。在检查探索结果 在父母试验中，来自三个VA中心的112名退伍军人，我们还将检查包括左边的心脏措施 心室质量，以及肌肉质量和身体性能的营养/身体功能指数。 我们提出的务实的RCT解决了退伍军人的主要未满足需求，ESRD启动了 透析通过专注于改善HRQOL和保存RKF，这是生存和生存的两个最强预测指标 患者满意。这项研究的结果可能使更多的退伍军人能够接受基于VA的治疗 透析中心。我们的研究可能会导致范式转变，并立即影响退伍军人的肾脏护理和 在更广泛的ESRD人群中。务实的设计将允许快速扩大干预措施 较大的设置以来，自RCT利用了VA中随时可用的资源和人员 全国多个VA地点的经验丰富的调查员和临床医生的中心。这提出了 研究对透析治疗的第一年中目前的三次高清护理标准提出了挑战， 在此期间，患者的痛苦和死亡率最高，营利性支持不太可能支持 如果每周两次高清实施，则透析提供者认为收入减少了。