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

项目总结 每年约有12,000名退伍军人发展为终末期肾病(ESRD)并开始透析 治疗。这些患者占美国ESRD发病人口的10%。透析费用昂贵，而且 与健康相关的生活质量受损(HRQOL)和高死亡风险有关，特别是在第一 透析年。目前的治疗模式是每周三次全剂量血液透析(HD)。 与患者的残余肾功能(RKF)无关，这种突然的转变增加了患者和护理- 这可能会增加伴侣的负担和痛苦，并可能限制他们的偏好。此外，最近的证据表明， 与在非退伍军人中心接受治疗的退伍军人相比，在退伍军人中心接受透析的退伍军人存活率更高。 尽管目前不是护理的标准，但有证据表明，逐步或递增的透析 使用初始的每周两次HD计划的过渡可能会带来实质性的好处，包括更多的透析- 自由时间，RKF保存时间更长，血管通路寿命更长，透析中低血压和终末器官减少 减少损伤，减少透析后的疲劳，减少患者的痛苦。因此，渐进式透析过渡 可以通过改善身体功能、减少疲劳、增加精力和 通过减轻日常生活中过度透析的负担，提高患者满意度和生活参与度。 迫切需要具有直接临床影响的务实研究，将透析的重点从 突然，每周三次的HD开始了安全有效的个性化透析方案。此外，实现 每周两次的HD计划将允许20%的退伍军人在退伍军人管理局的透析单元内接受护理。 本着RFA CX-21-006进行临床试验的精神，在这个多PI、多部位、务实、1：1的随机对照试验中 对照试验(RCT)，在退伍军人常规透析治疗的同时，我们将测试一种 每周两次的增量HD方案，与每周三次的标准护理方案相比，在满足 预定义的资格标准。我们计划将每周两次(增量)与每周三次(常规)进行比较 252名发生终末期SRD的退伍军人开始HD治疗，他们将在6个VA过渡到维持性HD治疗 中锋。使用长达12个月的季度评估，我们将检查简表36(SF36)HRQOL 作为主要结果的身体成分评分，以及透析症状指数和SF36能量/ 疲劳评分作为次要终点。其他次要成果将包括保留RKF， 每季度测量透析充分性、营养状况和蛋白质-能量消耗指标。安全问题 评估将包括死亡率、停止透析、急诊室就诊、住院治疗、 高钾血症和严重的心血管不良事件。在一项考察探索性结果的子研究中 来自三个退伍军人中心的112名退伍军人参加了家长试验，我们还将检查包括Left在内的心脏测量 心脏重量，以及肌肉质量和体能的营养/身体功能指数。 我们建议的实用RCT解决了退伍军人中未得到满足的主要需求，事件ESRD启动 通过专注于改善HRQOL和保存RKF进行透析，这两个最强的生存和 病人满意度。这项研究的结果可能使更多的退伍军人能够在退伍军人管理局接受治疗 透析中心。我们的研究可能会导致一种范式的转变，对退伍军人和 在更广泛的ESRD人群中。务实的设计将使干预措施迅速扩大到 更大的设置，因为RCT利用了退伍军人管理局随时可用的资源和人员 中心在经验丰富的研究人员和临床医生的带领下，遍布全国多个退伍军人事务部。这项建议 这项研究挑战了目前在透析治疗的第一年每周三次HD的护理标准， 在此期间，患者的痛苦和死亡率最高，而且不太可能得到营利性组织的支持 考虑到如果要广泛实施每周两次HD，透析提供商的收入将明显减少。

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.