HiLo

随着人口老龄化和治疗进步提高慢性病的预期寿命，患病率 终末期肾病(ESRD)的发病率无情地增加。肾移植是首选的治疗方法，但 器官供应不足使透析成为大多数患者唯一的治疗选择。虽然透析 近年来，结果略有改善，年住院率和死亡率保持不变。 高得令人无法接受，生活质量很差。渴望治疗方面的进步以改善结果， 肾脏病学界对ESRD护理的许多方面采用了基于意见的临床实践指南， 包括我们控制磷酸盐的方法。目前的指导方针主张积极治疗 高磷血症至接近正常水平(&lt；5.0 mg/dl)，使用膳食磷酸盐结合剂和高度限制 饮食；然而，由于还没有随机的临床结果试验，这一假设的好处 方法未经证实，潜在的危害尚未确定，最佳的血清磷酸盐目标是 未知。为了解决这一重要的未得到满足的需求，我们提出了一项大型、整群随机的实用试验HILO 将作为NIH卫生保健系统研究合作实验室的示范项目之一进行。 希洛将评估放开患者血磷指标对重要临床结局的影响 接受维持性血液透析治疗。这项试验将招募4400名患者，并将完全嵌入 在由三个透析提供商组织拥有和运营的&gt；100个透析设施的临床护理中： 一家大型的全国性营利性透析公司，一家中型非营利性透析公司，以及一家学术拥有的 区域提供商。希洛将检验这一假设，即自由地将血磷控制在6-7毫克/分升的目标将 与目前以磷酸盐为目标的标准方法相比，收益率不低于住院率 水平为&lt；5.0 mg/dl。作为次要目标，希洛将测试不同武器在死亡率方面的优势。 希洛数据协调中心将设在杜克临床研究所(DCRI)，这是一个高度 经验丰富的学术研究机构和合作实验室协调中心。该项目将 将分两个阶段实施--UG3规划阶段和UH3实施阶段--每个阶段都有 具体的里程碑。除了解决与ESRD高度临床相关的问题外，Hilo还将推进 通过几项创新的实用试验领域：1)回答一个紧迫的临床问题，而不是 评估战略，以加强已证实的治疗的实施；2)使用新的电子方法 患者级别的同意，使务实的评估“超过最低风险”的干预首次 ESRD；以及3)为ESRD试验中的非死亡率主要终点提供了先例。鉴于……的重要性 向患者、临床医生、透析提供者和付款人提出的试验问题，以及“真实世界”的测试方法 在实施干预措施后，希洛研究所的调查结果将迅速实施，并在完成 审判。此外，重要的是，希洛将为ESRD和更广泛的未来务实试验铺平道路。

As the population ages and therapeutic advances improve life expectancies of chronic diseases, the prevalence of end-stage renal disease (ESRD) inexorably increases. Kidney transplantation is the preferred treatment, but an insufficient organ supply renders dialysis the only treatment option for most patients. Although dialysis outcomes have improved modestly in recent years, annual rates of hospitalizations and mortality remain unacceptably high and quality of life is poor. Starved for therapeutic advances to improve outcomes, the nephrology community has adopted opinion-based clinical practice guidelines for many aspects of ESRD care, including our approach to phosphate control. Current guidelines advocate aggressive treatment of hyperphosphatemia to near normal levels (< 5.0 mg/dl) using dietary phosphate binders and highly restrictive diets; however, because there have been no randomized clinical outcomes trials, the assumed benefits of this approach are unproven, potential harms have not been identified, and the optimal serum phosphate target is unknown. To address this important unmet need, we propose “HiLo”, a large, cluster-randomized pragmatic trial to be conducted as one of the demonstration projects of the NIH Health Care Systems Research Collaboratory. HiLo will evaluate the effects on important clinical outcomes of liberalizing serum phosphate target for patients receiving treatment with maintenance hemodialysis. The trial will enroll 4400 patients and will be fully embedded in the clinical care delivery of >100 dialysis facilities owned and operated by three dialysis provider organizations: a large, national for-profit dialysis company, a mid-sized non-profit dialysis company, and an academically-owned regional provider. HiLo will test the hypothesis that liberal control of serum phosphate to target 6–7 mg/dl will yield non-inferior rates of hospitalization compared to the current standard approach of targeting phosphate levels to <5.0 mg/dl. As a secondary objective, HiLo will test for superiority of the different arms on mortality. The HiLo Data Coordinating Center will be based at the Duke Clinical Research Institute (DCRI), a highly experienced academic research organization and the Coordinating Center for the Collaboratory. The project will be implemented in two phases – a UG3 planning phase and a UH3 implementation phase – each of which has specific milestones. In addition to addressing a question of high clinical relevance in ESRD, HiLo will advance the field of pragmatic trials through several innovations: 1) answering a pressing clinical question rather than evaluating strategies to enhance implementation of a proven therapy; 2) using a novel electronic approach for patient-level consent to enable pragmatic evaluation of a “more than minimal risk” intervention for the first time in ESRD; and 3) providing a precedent for a non-mortality primary endpoint in ESRD trials. Given the importance of the trial question to patients, clinicians, dialysis providers, and payers, and the “real-world” approach to testing the intervention, the findings of HiLo will be rapidly implemented and readily sustained upon completion of the trial. Additionally, and importantly, HiLo will pave the way for future pragmatic trials in ESRD and more broadly.