Applying Hypertension Clinical Trials to Real World Adults with CKD

将高血压临床试验应用于现实世界中患有 CKD 的成人

• 批准号: 10494235
• 负责人: MANJULA KURELLA TAMURA
• 金额: $ 64.94万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494235
• 关键词: Adult; Affect; African American; Attenuated; Benefits and Risks; Blood Pressure; California; Cardiovascular system; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Trials; Consensus; Data; Databases; Decision Making; Diabetes Mellitus; Disease Management; Disease Progression; Elderly; Electronic Health Record; Event; Goals; Guidelines; Healthcare Systems; Hypertension; Individual; Intervention Trial; Kidney; Kidney Diseases; Laboratories; Lead; Modeling; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacy facility; Population; Recommendation; Renal function; Research Priority; Risk; Secondary Prevention; Serious Adverse Event; Stroke; Subgroup; Target Populations; Uncertainty; Veterans Health Administration; blood pressure intervention; blood pressure medication; cardiovascular risk factor; clinical decision support; cohort; comparative; high risk population; hypertension control; hypertension treatment; innovation; mortality; mortality risk; novel; patient population; personalized predictions; profiles in patients; randomized trial; symposium; treatment effect

PROJECT SUMMARY / ABSTRACT Hypertension affects more than 80% of adults with chronic kidney disease (CKD), and its treatment is a cornerstone of CKD management. Clinical guidelines vary in their recommendations for blood pressure targets in CKD, reflecting uncertainties in the interpretation of the Systolic Blood Pressure Intervention Trial (SPRINT) and its extrapolation to adults with CKD, particularly those with advanced CKD. Although evidence from randomized trials has strong internal validity, it may not reflect the risk benefit profile of patient populations that will receive treatment in practice. Our overarching goal is to evaluate the comparative risks and benefits of intensive versus standard blood pressure targets in real world adults with CKD. Our secondary goal is to demonstrate the feasibility and utility of novel analytical approaches that extend causal effects from randomized trial effects to broader populations. We will accomplish these goals by leveraging electronic health record data from two large health care systems encompassing 13 million enrollees - the Veterans Health Administration and Kaiser Permanente of Southern California. To inform our real-world estimates, we will integrate individual-level data from four diverse hypertension trials on 20,000 participants. In Aim 1, we will estimate average treatment effects of intensive versus standard blood pressure targets among SPRINT-eligible real world adults with CKD. In Aim 2, we will develop and validate models for individualized prediction of intensive blood pressure treatment effects, and illustrate the application in real world CKD populations. In Aim 3, we will emulate a sequential clinical trial of blood pressure medication intensification using electronic health records in persons with CKD. Our study is important because hypertension treatment affects nearly all adults with CKD and key evidence gaps may lead to suboptimal management in this high-risk population. It is innovative because it will provide new evidence about the implications of intensive blood pressure targets and new analytic approaches to support clinical decisions with real world data.

项目摘要/摘要 高血压影响着80%以上患有慢性肾脏病(CKD)的成年人，其治疗是一种 CKD管理的基石。临床指南对血压指标的建议各不相同 在慢性肾脏病中，反映了对收缩压干预试验(SPRINT)解释的不确定性 并将其外推到成人CKD患者，特别是晚期CKD患者。尽管证据来自 随机试验具有很强的内部有效性，它可能不能反映患者群体的风险收益概况 将在实践中接受治疗。我们的首要目标是评估以下各项的相对风险和收益 现实世界中患有慢性肾脏病的成年人的强化血压指标与标准血压指标。我们的次要目标是 论证新的分析方法的可行性和实用性，这些方法将因果关系从 对更广泛人群的随机试验效果。我们将通过利用电子健康来实现这些目标 来自两个涵盖1300万参保者的大型医疗保健系统的创纪录数据-退伍军人健康 南加州的行政当局和凯撒长老。为了通知我们现实世界的估计，我们将 整合来自四个不同高血压试验的个体水平的数据，这些试验涉及20,000名参与者。在目标1中，我们将 在符合短跑条件的人群中评估强化与标准血压指标的平均治疗效果 现实世界中患有慢性肾脏病的成年人。在目标2中，我们将开发和验证个性化预测模型 强化血压治疗效果，并举例说明其在现实世界CKD人群中的应用。在AIM 3、我们将利用电子健康模拟降压药物强化的序贯临床试验 慢性肾脏病患者的记录。我们的研究很重要，因为高血压治疗几乎影响到所有成年人 对于慢性肾脏病和关键证据，差距可能导致在这一高危人群中进行次优管理。它是 创新是因为它将提供关于高强度血压目标和 使用真实数据支持临床决策的新分析方法。