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，影响了超过900万美国成年人，患有疾病 负担在全球上升。尽管有很大的临床后果，但痛风护理仍然不一致，很大 证据基础的差距。异质痛风护理的主要贡献者是对 由于缺乏高级证据，实现目标血清尿酸盐（SU）的价值。风湿病 指南强调了一种靶向血清尿酸盐（TTT-SU）方法的治疗方法（例如，su <6 mg/dl，尿酸盐子 - 饱和点）;但是，引用没有证据的话，SU甚至在降低尿酸盐中也没有测量 在初级保健实践中，绝大多数痛风患者的治疗，> 90％的痛风护理发生。我们 旨在通过动员风湿病学家和主要的主要证据产生高级证据来解决指南冲突 护理提供者（PCP）。此外，痛风是一种代谢状况，由于心肌的高风险而复杂 梗塞，糖尿病，慢性肾脏疾病和过早死亡，尽管痛风是否尚不清楚 因果关系导致这些结果。通过降低SU去除单钠晶体晶体沉积可以减少 痛苦的炎症，可能是通过钝化炎症途径。但是，尚不清楚是否降低su 导致肾脏损伤较小，血糖控制更好或降低心血管风险。 NIH资金使我们能够在2018年召集一次会议（R13AR073116）与PCP和风湿病学家召开会议 检查现有数据，定义争议，并在必要的信息上输入输入以填充 关键的证据差距。在这次会议上，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年中，我们开展了关键活动，以获取从 所有相关利益相关者。经过修改的Delphi面板，包括痛风患者，护士和医师助理， PCP和风湿病学家就关键协议决策提出了共识。模拟招聘活动 允许我们测试和完善可行程序，从而导致成功的筛查，筛选和 在拟议的多站点RCT期间，患者招募以下两个目标。 目的1）在痛风和高尿素（HU）患者中进行将TTASX与TTT-SU进行比较的RCT。 我们已经为所有相关利益相关者提供了可以接受的试验协议，这将有效地回答 TTT-SU策略导致痛风耀斑（主要结果）的主要假设 两年的随访比TTASX。为了确保平衡性和普遍性，我们将从PCP招募患者 实践。目标2）测试降低SU对肾功能，血糖状态和血压的影响 在痛风患者中，参加了RCT。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）估计肾小球的下降较慢 过滤率； b）较低的HBA1C; c）痛风患者的血压改善。