A pilot study to target out-of-dialysis-unit versus dialysis-unit blood pressure

项目总结 我们的长期目标是改变维持性血液透析(HD)的血压管理模式 以改善患者的临床结果。我们的假设是，心血管疾病(CVD)的风险事件和死亡率 如果医生测量和治疗透析外单位血压，而不是透析单位血压，HD患者的血压会降低 目前的做法和指南所建议的。这一假设是基于我们小组的新观察数据 还有其他人。我们最近在一组多中心的HD事件患者队列中显示，虽然有一种“自相矛盾的”U- 在透析单位收缩压(SBP)与全因死亡和心血管事件的风险之间形成关联，存在 在透析单元外测量的SBP与死亡和心血管事件的风险之间的线性逐步关联 与普通人群相似的模式。 由于透析单元和透析单元外SBP之间的相关性较差，靶向透析单元SBP可能会导致 相当数量的患者过度治疗(高透析单元但低透析单元外SBP的患者)。这 可能导致透析中的低血压、心肌顿抑和不利的心脏重塑。同时，其他患者 可能治疗不足(透析单元SBP低但透析外SBP高的患者)，这可能导致终末器官 损坏。 在本申请中，我们建议进行一项双中心试点临床试验，以测试靶向和安全性的可行性和安全性。 透析外单元(家庭)SBP目标为&lt；140 mm Hg，而透析单元(透析前)SBP目标为&lt；140 mm Hg/50 流行的HD患者采用了干体重和BP用药调整的算法。为促进务实和 临床上可行的透析外/家庭血压读数的方法，我们将测试一种经过验证的移动健康血压监测仪 能够进行蓝牙数据传输。 具体目标是：1)确定干重调整和反污染战略的可行性和坚持性。 高血压药物滴定实现透析外单位(家庭)SBP&lt；140毫米汞柱与透析单位(前) 透析)SBP&lt；在6个月内140毫米汞柱；2)测试干预的安全性和耐受性，以实现出院 透析-单位(家庭)收缩压及140毫米汞柱。 这项试点试验将是帮助设计一项大型、多中心临床试验的关键中间步骤，以测试靶向 维持性血液透析患者的透析单元外(家庭)SBP与透析单元(透析前)SBP将降低 维持性血液透析患者心血管事件与死亡率的关系来自这项研究的数据将用于测试研究物流，优化 研究干预，确定实施的障碍和促进者，并获得研究参数的经验估计 以帮助设计最终的临床试验。

PROJECT SUMMARY Our long-term goal is to change the paradigm of blood pressure (BP) management in maintenance hemodialysis (HD) patients to improve clinical outcomes. Our hypothesis is that risk cardiovascular disease (CVD) events and mortality will be lowered in HD patients if physicians measure and treat out-of-dialysis-unit BP, rather than dialysis-unit BP, which is the current practice and what guidelines recommend. This hypothesis is based on novel observation data from our group and others. We recently showed in a multi-center cohort of incident HD patients that while there was a “paradoxical” U- shaped association between dialysis-unit systolic BP (SBP) and risk of all-cause mortality and CVD events, there was a linear stepwise association between SBP measured outside of the dialysis-unit and risk of mortality and CVD events, in a pattern similar to that in the general population. Since there is poor correlation between dialysis-unit and out-of-dialysis-unit SBP, targeting dialysis-unit SBP may lead to overtreatment in a substantial number of patients (those with high dialysis-unit but low out-of-dialysis-unit SBP). This may cause intra-dialytic hypotension, myocardial stunning and adverse cardiac remodeling. Concurrently, other patients may be undertreated (those with low dialysis-unit SBP but high out-of-dialysis-unit SBP), which may result in end-organ damage. In this application, we propose to conduct a two-center pilot clinical trial to test the feasibility and safety of targeting an out-of-dialysis-unit (home) SBP goal of <140 mmHg vs. a dialysis-unit (pre-dialysis) SBP goal of <140 mmHg among 50 prevalent HD patients using an algorithm of dry weight and BP medication adjustment. To facilitate a pragmatic and clinically feasible approach to out-of-dialysis-unit/home BP readings, we will test a validated mobile health BP monitor capable of Bluetooth enabled data transmission. The specific aims are: 1) to determine the feasibility of and adherence to a strategy of dry weight adjustment and anti- hypertensive medication titration to achieve an out-of-dialysis-unit (home) SBP <140 mmHg vs. a dialysis-unit (pre- dialysis) SBP <140 mmHg over 6 months and 2) to test the safety and tolerability of an intervention to achieve out-of- dialysis-unit (home) systolic blood pressure <140 mmHg. This pilot trial will be a key intermediate step to help design a large, multi-center clinical trial to test whether targeting out-of-dialysis-unit (home) SBP vs. dialysis-unit (pre-dialysis) SBP among maintenance HD patients will reduce rates of CVD events and mortality in maintenance HD patients. Data from this study will be to test study logistics, optimize the study intervention, identify barriers and facilitators of implementation and obtain empirical estimates of study parameters to help design the definitive clinical trial.