HiLo

高低

基本信息

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
项目类别：
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

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.

随着人口老龄化和治疗方法的进步提高了慢性病的预期寿命，患病率终末期肾病（ESRD）的发病率不可避免地增加，但肾移植是首选治疗方法。器官供应不足使得透析成为大多数患者唯一的治疗选择。近年来，结果略有改善，年住院率和死亡率仍然存在患者的生活质量高得令人难以接受，而生活质量却很差。肾病学界针对 ESRD 护理的许多方面采用了基于意见的临床实践指南，包括我们当前的磷酸盐控制方法提倡积极治疗。使用膳食磷酸盐结合剂和严格限制将高磷血症降至接近正常水平（< 5.0 mg/dl）饮食；然而，由于还没有随机临床结果试验，因此假设的好处方法未经证实，潜在危害尚未确定，最佳血清磷酸盐目标是为了解决这一重要的未满足需求，我们提出了“HiLo”，这是一项大型、整群随机的实用试验。将作为 NIH 医疗保健系统研究合作实验室的示范项目之一进行。 HiLo 将评估放开患者血清磷酸盐目标对重要临床结果的影响该试验将招募 4400 名接受维持性血液透析治疗的患者，并将全面纳入其中。在三个透析提供者组织拥有和运营的超过 100 个透析设施的临床护理服务中：一家大型全国性营利性透析公司、一家中型非营利性透析公司和一家学术拥有的透析公司 HiLo 将检验将血清磷酸盐自由控制至 6-7 mg/dl 的假设。与当前针对磷酸盐的标准方法相比，住院率不低水平<5.0 mg/dl 作为次要目标，HiLo 将测试不同组在死亡率方面的优越性。 HiLo 数据协调中心将设在杜克临床研究所 (DCRI)，该研究所是一家经验丰富的学术研究组织和该项目的协调中心将。分两个阶段实施——UG3规划阶段和UH3实施阶段——每个阶段都有除了解决 ESRD 的高度临床相关性问题外，HiLo 还将取得进展。务实试验领域通过多项创新：1）回答紧迫的临床问题，而不是评估策略以加强已证实的疗法的实施；2）使用新颖的电子方法患者层面的同意，以便首次能够对“大于最小风险”的干预进行务实评估 ESRD；3) 考虑到 ESRD 试验的重要性，为非死亡主要终点提供了先例。向患者、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后，HiLo 的调查结果将得到迅速实施，并在完成后很容易得到维持此外，重要的是，HiLo 将为未来 ESRD 及更广泛领域的实用试验铺平道路。