Treat-to-Target Serum Urate versus Treat-to-Avoid Symptoms in Gout: A Randomized Controlled Trial (TRUST)

治疗痛风目标血清尿酸与治疗避免症状：随机对照试验 (TRUST)

• 批准号: 10583217
• 负责人: MICHAEL J BARRY
• 金额: $ 204.61万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583217
• 关键词: Accident and Emergency department; Acute; Address; Adult; Affect; Agreement; American; American College of Physicians; Arterial Fatty Streak; Arthritis; Blinded; Blood Pressure; Cardiac; Cardiology; Cardiovascular system; Caring; Cessation of life; Cholesterol; Chronic; Chronic Kidney Failure; Clinical; Clinical Trials; Conflict (Psychology); Consensus; Coronary artery; Crystal Formation; Data; Deposition; Diabetes Mellitus; Enrollment; Ensure; Equipoise; Flare; Funding; Genetic; Glomerular Filtration Rate; Glycosylated hemoglobin A; Gout; Guidelines; Hyperuricemia; Inflammasome; Inflammation; Inflammatory; Inflammatory Arthritis; Infrastructure; Intervention; Kidney; Kidney Diseases; Letters; Level of Evidence; Measures; Metabolic; Methods; Myocardial Infarction; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Nephrology; Nurse Practitioners; Nurses; Outcome; Pain; Pathway interactions; Patient Recruitments; Patients; Phenotype; Physician Assistants; Play; Procedures; Protocols documentation; Quality of life; Randomized; Randomized, Controlled Trials; Recruitment Activity; Renal function; Reporting; Research Personnel; Resources; Rheumatology; Risk; Role; Running; Science; Serum; Site; Specialist; Subgroup; Surrogate Markers; Symptoms; Testing; United States National Institutes of Health; Urate; Visit; Work; X-Ray Computed Tomography; arm; arthropathies; biobank; bone erosion; burden of illness; cardiovascular risk factor; cohort; cost effective; evidence base; follow-up; glycemic control; high risk; improved; incremental cost; insight; interest; joint injury; participant enrollment; patient subsets; premature; primary care practice; primary care provider; primary outcome; randomized trial; recruit; renal damage; rheumatologist; screening; symposium; trial comparing

ABSTRACT Gout is the most common inflammatory arthritis, affecting more than 9 million American adults, with a disease burden rising worldwide. Despite substantial clinical consequences, gout care is inconsistent, with considerable gaps in the evidence base. The primary contributor to heterogeneous gout care is a lack of agreement about the value of achieving a target serum urate (SU), due to a lack of high-level evidence. Rheumatology guidelines emphasize a treat to target serum urate (TTT-SU) approach (e.g., SU <6 mg/dL, a urate sub- saturation point); however, citing the absence of evidence, SU is not even measured during urate-lowering therapy in the vast majority of gout patients in primary care practice, where >90% of gout care occurs. We aim to generate high-level evidence to resolve the guideline conflict by mobilizing rheumatologists and primary care providers (PCPs). Furthermore, gout is a metabolic condition complicated by a high risk of myocardial infarction, diabetes, chronic kidney disease, and premature death, although it remains unknown whether gout causally leads to these outcomes. Removing monosodium urate crystal deposition by lowering SU can reduce gouty inflammation, likely by blunting the inflammasome pathway. However, it is unknown whether lowering SU results in less kidney damage, better glycemic control, or reduced cardiovascular risk. NIH funding allowed us to convene a conference in 2018 (R13AR073116) with PCPs and rheumatologists to examine the existing data, define the controversies, and elicit input on the necessary information to fill the critical evidence gap. Informed by this conference, we received funding in 2020 (AR076077) to plan a randomized controlled trial (RCT). During the past 1.5 years, we carried out key activities to gain insights from all relevant stakeholders. A modified Delphi Panel, including gout patients, nurses and physician assistants, PCPs, and rheumatologists, came to consensus regarding key protocol decisions. Mock recruitment activities allowed us to test and refine feasible procedures which will lead to successful pre-screening, screening, and patient recruitment during the proposed multi-site RCT with the following two aims. Aim 1) To conduct a RCT comparing TTASx with TTT-SU among patients with gout and hyperuricemia (HU). We have developed a trial protocol acceptable for all relevant stakeholders that will effectively answer the primary hypothesis that a TTT-SU strategy results in significantly fewer gout flares (primary outcome) over a two-year follow-up than TTASx. To ensure equipoise and generalizability, we will recruit patients from PCP practices. Aim 2) To test the effects of lowering SU on kidney function, glycemic status, and blood pressure among patients with gout enrolled in the RCT. The corresponding hypotheses are that lowering SU to a greater extent in the TTT-SU arm compared with TTASx will result in: a) slower decline in estimated glomerular filtration rate; b) lower HbA1c; and c) improved blood pressure in gout patients.

摘要 痛风是最常见的炎症性关节炎，影响着900多万美国成年人的疾病 全球范围内的负担正在上升。尽管有重大的临床后果，但痛风治疗是不一致的，有相当大的 证据基础上的空白。不同种类的痛风护理的主要原因是缺乏关于 由于缺乏高水平的证据，实现目标血尿酸(SU)的价值。风湿病 指南强调治疗靶向血清尿酸盐(TTT-SU)的方法(例如，SU&lt；6 mg/dL，一种尿酸盐亚单位 饱和点)；然而，由于缺乏证据，在降低尿酸的过程中甚至没有测量SU 绝大多数痛风患者的治疗是在初级保健实践中进行的，那里&gt；90%的痛风护理发生在那里。我们 目的通过动员风湿科医生和初级医生来产生高水平的证据来解决指南冲突 护理提供者(PCP)。此外，痛风是一种代谢疾病，并有较高的心肌梗死风险。 梗塞、糖尿病、慢性肾脏疾病和过早死亡，尽管目前尚不清楚痛风 因果关系导致了这些结果。降低宿灿还原消除尿酸钠结晶沉积 痛风性炎症，可能是通过钝化炎症小体途径。然而，目前尚不清楚是否会降低SU 结果更少的肾脏损害，更好的血糖控制，或降低心血管风险。 NIH的资金使我们能够在2018年召开一次会议(R13AR073116)，与儿科医生和风湿病专家一起 检查现有数据，定义争议，并就必要的信息征求意见，以填补 关键证据差距。受这次会议的影响，我们在2020年(AR076077)获得资金，计划 随机对照试验(RCT)。在过去的1.5年里，我们开展了一些关键活动，以深入了解 所有相关的利益相关者。一个改良的德尔福小组，包括痛风患者、护士和医生助理， PCP和风湿病学家就关键的方案决定达成了共识。模拟招聘活动 使我们能够测试和改进可行的程序，这些程序将导致成功的预筛选、筛选和 在拟议的多地点随机对照试验期间招募患者，有以下两个目标。 目的1)对痛风合并高尿酸血症(HU)患者的TTASx和TTT-SU进行随机对照研究。 我们已经制定了一个所有相关利益相关者都可以接受的试验方案，该方案将有效地回答 主要假设TTT-SU策略可显著减少痛风发作(主要结果) 比TTASx随访两年。为了确保均衡性和普适性，我们将从PCP招募患者 练习。目的2)检测降低SU对肾功能、血糖和血压的影响 在纳入随机对照试验的痛风患者中。相应的假设是，将SU降低到更大 与TTASx相比，TTT-SU臂的范围将导致：a)估计的肾小球下降较慢 滤过率；b)降低HbA1c；以及c)改善痛风患者的血压。