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.

抽象的 痛风是最常见的炎症性关节炎，影响超过 900 万美国成年人。 全球负担不断加重。尽管有重大的临床后果，但痛风治疗并不一致，相当多的患者 证据基础上的差距。痛风护理异质性的主要原因是缺乏共识 由于缺乏高级证据，实现目标血清尿酸（SU）的价值。风湿病学 指南强调以血清尿酸盐为目标（TTT-SU）的治疗方法（例如，SU <6 mg/dL，尿酸盐亚 饱和点）；然而，由于缺乏证据，在降尿酸期间甚至没有测量 SU 绝大多数痛风患者在初级保健实践中接受治疗，其中超过 90% 的痛风护理发生在初级保健实践中。我们 旨在通过动员风湿病学家和基层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，痛风是一种代谢性疾病，伴有心肌梗死的高风险。 梗塞、糖尿病、慢性肾病和过早死亡，尽管目前尚不清楚痛风是否 因果关系导致这些结果。通过降低SU去除尿酸单钠晶体沉积可以减少 痛风性炎症，可能是通过削弱炎症小体途径来实现的。但是否会降低 SU 尚不清楚 可以减少肾脏损伤，更好地控制血糖，或降低心血管风险。 NIH 的资助使我们能够在 2018 年与 PCP 和风湿病学家召开一次会议 (R13AR073116)，以 检查现有数据，定义争议，并征求必要信息的输入以填补问题 关键证据差距。根据这次会议，我们在 2020 年获得了资金（AR076077）来计划 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，以获取见解 所有相关利益相关者。修改后的德尔菲小组，包括痛风患者、护士和医师助理， PCP 和风湿病学家就关键方案决策达成共识。模拟招聘活动 使我们能够测试和完善可行的程序，这将导致成功的预筛选、筛选和 在拟议的多中心随机对照试验期间招募患者有以下两个目的。 目标 1) 开展一项随机对照试验，在痛风和高尿酸血症 (HU) 患者中比较 TTASx 与 TTT-SU。 我们已经制定了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问题 主要假设是，与 TTT-SU 策略相比，TTT-SU 策略可显着减少痛风发作（主要结果） 比 TTASx 进行了两年的随访。为了确保均衡性和普遍性，我们将从 PCP 招募患者 做法。目标 2) 测试降低 SU 对肾功能、血糖状态和血压的影响 参加随机对照试验的痛风患者。相应的假设是将 SU 降低到更大 与 TTASx 相比，TTT-SU 组的程度将导致：a) 估计肾小球下降较慢 过滤率； b) 降低 HbA1c； c) 改善痛风患者的血压。