HiLo

高低

基本信息

批准号：
10468020
负责人：
MYLES S WOLF
金额：
$ 129.83万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10468020
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 Placebo Control 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

项目摘要

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.

随着人口的年龄和治疗进展提高了慢性疾病的预期寿命，流行率末期肾脏疾病（ESRD）的不可分割增加。肾脏移植是首选的治疗方法，但器官供应不足使透析是大多数患者的唯一治疗选择。虽然透析近年来，结果均未改善，住院和死亡率的年率仍然无法接受的高质量和生活质量很差。为了改善预后的治疗进展而饿死肾脏科社区已针对ESRD护理的许多方面采用了基于意见的临床实践指南，包括我们对磷酸盐控制的方法。当前指南提倡对使用饮食中的磷酸盐结合剂和高度限制性饮食；但是，由于没有随机临床结果试验，因此假定的好处方法未经证实，尚未确定潜在危害，最佳的血清磷酸盐靶标为未知。为了满足这一重要的未满足需求，我们提出了“ Hilo”，这是一项大型的，随机的务实试验作为NIH医疗保健系统研究合作社的演示项目之一。希洛将评估对患者宽松血清磷酸盐靶标的重要临床结果的影响接受维持血液透析治疗。该试验将注册4400名患者，并将完全嵌入在临床护理中，由三个透析提供者组织拥有和运营的100个透析设施> 100个透析设施：一家大型国家营利性透析公司，一家中型的非营利性透析公司和一家学术上的区域提供商。 Hilo将检验以下假设：血清磷酸盐对目标6-7 mg/dl的自由控制将与靶向磷酸盐的当前标准方法相比，住院的非上限率水平<5.0 mg/dl。作为次要目标，希洛将测试不同臂在死亡率上的优越性。 HILO数据协调中心将位于杜克临床研究所（DCRI），这是一个高度经验丰富的学术研究组织和协调中心合作中心。该项目将可以分为两个阶段 - UG3计划阶段和一个UH3实施阶段 - 每个阶段都有具体的里程碑。除了解决ESRD中高临床相关性的问题外，希洛还将进步通过几项创新进行了务实试验领域：1）回答紧迫的临床问题，而不是评估增强实施良好疗法的策略； 2）使用一种新型的电子方法患者级别同意首次对“超过最小风险”干预的务实评估 ESRD; 3）在ESRD试验中为非验尸主要端点提供了先例。考虑到重要性对患者，临床医生，透析提供者和付款人以及测试的“现实世界”方法的审判问题干预措施，希洛的发现将在完成后迅速实施并很容易维持审判。此外，重要的是，希洛将为ESRD和更广泛的务实试验铺平道路。