Integrated Mineral Metabolism Treatment Strategies in Patients on Dialysis

透析患者的综合矿物质代谢治疗策略

• 批准号: 9219542
• 负责人: Julia J Scialla
• 金额: $ 51.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9219542
• 关键词: Admission activity; Advanced Practice Nurse; Adverse effects; Advocate; Age; Agonist; Area; Biochemical; Biological; Bone Diseases; Calcium; Calcium Binding; Calcium-Sensing Receptors; Cardiovascular Diseases; Caring; Characteristics; Clinic; Clinical; Clinical Data; Clinical Practice Guideline; Clinical Trials; Combined Modality Therapy; Data; Data Collection; Data Element; Dialysis patients; Dialysis procedure; Dose; Dropout; Drug toxicity; End stage renal failure; Equipoise; Event; Evidence based practice; Feedback; Focus Groups; Fracture; Goals; Guidelines; Hemodialysis; Hormones; Hospitalization; Hospitals; Hypercalcemia; Hypocalcemia result; Intention; Intervention; Interview; Investigation; Kidney; Knowledge; Laboratories; Lead; Link; Medical Records; Metabolism; Methods; Minerals; Modeling; Morbidity - disease rate; Nausea; Nutritionist; Observational Study; Outcome; PTH gene; Patient Care; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacology; Phosphorus; Physician Assistants; Physicians; Physiological; Placebos; Process; Provider; Quality of life; Randomized; Recommendation; Regimen; Risk; Risk Factors; Structural Models; Testing; Time; Translating; United States; Update; Variant; Vitamin D; adverse outcome; alternative treatment; base; cardiovascular risk factor; care delivery; clinical practice; clinical predictors; clinically relevant; common treatment; comparative effectiveness; design; effectiveness trial; fibroblast growth factor 23; gastrointestinal; health related quality of life; improved; mortality; patient population; peer; preclinical study; prevent; prospective; randomized trial; success; treatment choice; treatment strategy

PROJECT SUMMARY Patients with end stage kidney disease on dialysis have deranged mineral metabolism, including often severe changes in calcium, phosphorus, parathyroid hormone and the phosphorus-regulatory hormone fibroblast growth factor 23. Pre-clinical studies strongly suggest that these mineral metabolism abnormalities may directly increase risk of common morbidities in this group including cardiovascular and bone disease. These potential effects in pre-clinical studies are supported by observational studies in patients linking mineral metabolism abnormalities with morbidity and mortality. Although treatment of mineral metabolism derangements is widespread in practice, there are no definitive trials demonstrating the best approaches to prevent common adverse outcomes in patients on dialysis such as accelerated mortality, cardiovascular disease and frequent hospital admissions. This application will utilize clinical practice data as well as patient and provider engagement to design needed trials and overcome prior barriers to trial success such as high rates of mineral metabolism treatment discontinuation and change. Because (1) multiple classes of pharmacologic agents are available to treat mineral metabolism abnormalities; and, (2) guidelines advocate broad ranges for biochemical parameters, such as phosphorus and parathyroid hormone, providers have many choices for their overall approach to mineral metabolism treatment and demonstrate substantial variation in approaches. This proposal will leverage real-world practice data derived from detailed medical records and linked administrative claims in a large population of patients treated with in-center hemodialysis to understand alternative treatment strategies and compare their outcomes. Aim 1 will define common treatment strategies that incorporate different pharmacologic agent combinations, doses and mineral metabolite target values (i.e., integrated strategies), and identify predictors of different prescribing practices in this area using discrete choice models. Aim 2 will evaluate the prospective association of integrated treatment strategies with adverse clinical outcomes, including mortality, cardiovascular disease events, fracture, hospitalization and health-related quality of life. Unique data elements, such as frequently updated medication and clinical data and facility clustering are well-suited to marginal structural modeling and instrumental variable methods to better account for potential confounding. In Aim 3, focus groups and directed interviews with patients and dialysis care providers will be used to deeply evaluate underlying reasons for frequent discontinuation and change of the treatment strategy that plagued prior trials. Ultimately, these studies will identify alternative strategies that are practical in real-world settings, associated with the most optimal clinical outcomes and sustainable through optimized care delivery, thereby solidifying the evidence-base for practice in this pervasive aspect of dialysis care. Additionally, results will select intervention and comparator strategies, from among many possibilities, that may be most effective and sustainable for further testing in definitive trials.

项目概要 接受透析的终末期肾病患者的矿物质代谢紊乱，通常包括严重的矿物质代谢紊乱。 钙、磷、甲状旁腺激素和磷调节激素成纤维细胞的变化 生长因子 23。临床前研究强烈表明这些矿物质代谢异常可能 直接增加该群体常见疾病的风险，包括心血管和骨骼疾病。这些 临床前研究中的潜在影响得到了对患者进行的观察性研究的支持，这些研究将矿物质与矿物质联系起来 代谢异常与发病率和死亡率。虽然矿物质代谢治疗 混乱在实践中很普遍，但没有明确的试验证明最佳方法 预防透析患者常见的不良后果，例如加速死亡率、心血管疾病 疾病和频繁住院。该应用程序将利用临床实践数据以及患者 和提供商参与设计所需的试验并克服先前试验成功的障碍，例如高 矿物质代谢治疗停止和改变的比率。因为 (1) 多个类 可使用药物治疗矿物质代谢异常； (2) 指南倡导者 生化参数范围广泛，例如磷和甲状旁腺激素，提供者有很多 他们对矿物质代谢治疗的整体方法的选择，并证明了在 接近。该提案将利用来自详细医疗记录和数据的真实世界实践数据 将大量接受中心血液透析治疗的患者的行政要求联系起来，以了解 替代治疗策略并比较其结果。目标 1 将定义常见的治疗策略 结合了不同的药物组合、剂量和矿物质代谢目标值（即， 综合策略），并使用离散选择确定该领域不同处方实践的预测因素 模型。目标 2 将评估综合治疗策略与临床不良反应的前瞻性关联 结果，包括死亡率、心血管疾病事件、骨折、住院和健康相关 生活质量。独特的数据元素，例如经常更新的药物和临床数据和设施 聚类非常适合边际结构模型和工具变量方法，可以更好地解释 以防潜在的混淆。在目标 3 中，对患者和透析护理进行焦点小组讨论和直接访谈 提供商将用于深入评估频繁停产和变更的根本原因 困扰先前试验的治疗策略。最终，这些研究将确定替代策略 在现实环境中实用，与最佳临床结果相关并且可持续 优化护理服务，从而巩固透析这一普遍方面的实践证据基础 关心。此外，结果将从多种可能性中选择干预和比较策略， 这对于最终试验中的进一步测试可能是最有效和可持续的。