HiLo

高低

• 批准号: 10229378
• 负责人: MYLES S WOLF
• 金额: $ 132.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10229378
• 关键词: Address; Adherence; Adopted; Advocate; Affect; Age; Bioinformatics; Cardiovascular Diseases; Caring; Cessation of life; Chronic Disease; Clinical; Clinical Practice Guideline; Clinical Research; Clinical Trials; Communities; Complication; Consent; Data; Data Coordinating Center; Detection; Dialysis procedure; Diet; Eligibility Determination; End stage renal failure; Enrollment; Ensure; Equipoise; Ethics; Evaluation; Future; General Population; Guidelines; Healthcare Systems; Hemodialysis; Hospitalization; Individual; Informed Consent; Institutional Review Boards; Intake; Intervention; Kidney Transplantation; Lead; Life; Life Expectancy; Maintenance; Malnutrition; Metals; Monitor; Nephrology; Observational Study; Organ; Outcome; Patients; Phase; Placebos; Polymers; Population; Practice Guidelines; Prevalence; Process; Proteins; Protocols documentation; Provider; Quality Control; Quality of life; Randomized; Regimen; Research; Research Institute; Risk; Savings; Secure; Serum; Serum Albumin; Testing; Therapeutic; Time; Translating; United States; United States National Institutes of Health; absorption; aggressive therapy; arm; base; cardiovascular disorder risk; cardiovascular risk factor; care delivery; clinical care; clinically relevant; collaboratory; design; dietary; dissemination trial; early satiety; electronic data; experience; high risk; hospitalization rates; improved; improved outcome; innovation; inorganic phosphate; member; minimal risk; mortality; mortality risk; novel; open label; pill; pragmatic trial; prevent; primary endpoint; recruit; response; secondary endpoint; systems research; working group

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.

随着人口老龄化和治疗进展改善慢性病的预期寿命， 终末期肾病（ESRD）的发病率不可避免地增加。肾移植是首选的治疗方法，但 器官供应不足使得透析成为大多数患者的唯一治疗选择。虽然透析 近年来，尽管结果略有改善，但住院率和死亡率仍然保持在 高得令人无法接受，生活质量很差。渴望治疗进步以改善结果， 肾病学界已经在ESRD护理的许多方面采用了基于意见的临床实践指南， 包括我们对磷酸盐控制的方法。目前的指南提倡积极治疗 高磷血症接近正常水平（< 5.0 mg/dl），使用膳食磷结合剂和高度限制性 饮食;然而，由于没有随机临床结果试验，这种饮食的假定益处 方法未经证实，潜在危害尚未确定，最佳血清磷酸盐目标是 未知为了解决这一重要的未满足的需求，我们提出了“HiLo”，一个大型的，集群随机的务实试验 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。 HiLo将评估放宽患者血清磷目标对重要临床结局的影响 接受维持性血液透析治疗。该试验将入组4400例患者， 由三个透析提供商组织拥有和运营的超过100个透析设施的临床护理提供： 一家大型的全国性营利性透析公司，一家中型的非营利性透析公司，以及一家学术性的 区域供应商。HiLo将检验以下假设：将血清磷酸盐自由控制至目标6-7 mg/dl将 与目前的磷酸盐靶向标准方法相比，获得非劣效的住院率 水平<5.0 mg/dl。作为次要目的，HiLo将检验不同组在死亡率方面的优效性。 HiLo数据协调中心将设在杜克临床研究所（DCRI），该研究所是一个高度 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 分两个阶段实施-UG 3规划阶段和UH 3实施阶段-每个阶段都有 具体的里程碑。除了解决ESRD的高临床相关性问题外，HiLo还将推进 通过几个创新的务实试验领域：1）回答一个紧迫的临床问题，而不是 评估策略，以加强已证实的治疗的实施; 2）使用新的电子方法， 患者层面的同意，使务实的评价“超过最低风险”的干预措施，第一次在 ESRD; 3）为ESRD试验中的非死亡主要终点提供了先例。鉴于必须 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 干预措施，HiLo的调查结果将迅速实施，并在完成后随时保持 审判此外，重要的是，HiLo将为ESRD和更广泛的未来务实试验铺平道路。