Planning for a Trial of Comparative Effectiveness of Gout Management Strategies

规划痛风管理策略的比较有效性试验

• 批准号: 10177873
• 负责人: MICHAEL J BARRY
• 金额: $ 21.79万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-03 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177873
• 关键词: Accident and Emergency department; Acute; Adrenal Cortex Hormones; Advocate; Affect; Allopurinol; American; American College of Physicians; Anti-Inflammatory Agents; Arthritis; Biometry; Boston; Cardiology; Cardiovascular Diseases; Cardiovascular system; Caring; Chronic; Chronic Kidney Failure; Clinical; Clinical Trials; Colchicine; Communities; Consensus; Consent Forms; Contracts; Crystal Formation; Crystallization; Data; Diabetes Mellitus; Dose; Effectiveness; Equilibrium; European; Flare; Frequencies; Funding; Goals; Gout; Grant; Guidelines; Health; Impairment; Inflammatory Arthritis; Institutional Review Boards; International; Joints; Kidney; Lead; Manuals; Metabolic; Metabolic Diseases; Morbidity - disease rate; Nephrolithiasis; Nephrology; Non-Steroidal Anti-Inflammatory Agents; Nurses; Outcome; Pamphlets; Patients; Pharmaceutical Preparations; Primary Care Physician; Primary Health Care; Probenecid; Procedures; Process; Protocols documentation; Publishing; Recommendation; Research Personnel; Rheumatism; Rheumatology; Risk; Serum; Site; Symptoms; Testing; Training; United States National Institutes of Health; Urate; Visit; Work; arthropathies; base; bone erosion; cardiometabolism; college; comparative effectiveness trial; design; evidence base; feasibility trial; febuxostat; improved; joint injury; medical specialties; meetings; member; optimal treatments; prevent; recruit; rheumatologist; symposium; systematic review; treatment arm; treatment as usual; treatment strategy; trial design

Gout is the most common inflammatory arthritis, affecting approximately 9 million Americans. It is a chronic metabolic disease characterized by monosodium urate (MSU) crystal deposition in the joints and elsewhere. Gout causes its major morbidity through acute disabling arthritis flares that represent the most common cause of arthritis visits to US emergency departments; gout can also cause tophi, bone erosions, and a chronic arthropathy with joint damage, and is associated with cardiovascular-metabolic complications. Acute gout flares can be treated effectively with anti-inflammatory medications. When flares are frequent and burdensome enough, urate lowering therapy (ULT) can be administered to reduce the frequency, reduce tophi, and prevent other complications. Using ULT to reduce serum urate (SU) levels below 6.0 mg/dL (below the MSU saturation point) should dissolve MSU crystals, the likely culprit of gout flares, and mitigate other complications. This “treat to target” serum urate (TTT-SU) approach has been advocated by rheumatologists. However, the majority of gout cases are seen in primary care and many rheumatologists have concerns that primary care management of gout is not aggressive enough, with too high a threshold to initiate ULT, and use of insufficient doses of ULT to achieve the “target.” Under-treatment of gout may lead to impairments in patient function due to frequent flares and chronic tophaceous arthropathy with joint damage. However, the TTT-SU approach to manage gout is largely based on pathophysiologic rationale, rather than clinical trials. A recent systematic review for the American College of Physicians' (ACP) Clinical Guidelines Committee confirmed the effectiveness of anti-inflammatory medications for gout flares, and effectiveness of ULT for lowering the risk of acute attacks, but acknowledged, “treatment to a specific target level has not been tested” and “…we remain uncertain about the value of a treat- to-target strategy compared with a strategy of basing treatment intensity on minimizing symptoms.” The ACP gout management guideline neither recommended a specific threshold for the initiation of ULT, nor a specific SU treatment target. The rheumatology community reacted negatively to the ACP guideline, with the main concern being it might worsen the already suboptimal management of gout in primary care. To attempt to resolve this controversy, we convened an NIH-funded meeting in Boston in the Spring of 2018 that included key stakeholders in gout care. The consensus of this meeting was that a comparative effectiveness trial of strategies of gout management would be the best way to resolve the controversy in an evidence-based manner. Thus, our overarching goal is to design a trial that will fill critical evidence gaps and directly inform current practice. In this application, we propose the following aims to plan such a trial: 1) to conduct a Delphi Panel process to determine the optimal design and parameters for the proposed trial. 2) to prepare trial details, including the U01 proposal (which will be submitted during year two of the planning period) with a study protocol, training documents, manual of operating procedures, consent form, and investigator brochure, and perform a mock recruitment.

痛风是最常见的炎症性关节炎，影响约 900 万美国人，是一种慢性疾病。 以尿酸钠 (MSU) 晶体沉积在关节和其他部位为特征的代谢性疾病。 痛风的主要发病原因是急性致残性关节炎发作，这是最常见的原因 到美国急诊科就诊的关节炎患者中，痛风还可能导致痛风石、骨质侵蚀和慢性疼痛。 关节病伴有关节损伤，并与急性痛风发作有关。 当发作频繁且造成负担时，可以使用抗炎药物进行有效治疗。 可以进行降尿酸治疗 (ULT) 以减少频率、减少痛风石并预防其他 使用 ULT 将血清尿酸 (SU) 水平降至 6.0 mg/dL 以下（低于 MSU 饱和点）。 应该溶解 MSU 晶体（痛风发作的可能罪魁祸首），并减轻其他并发症。 “目标”血清尿酸盐（TTT-SU）方法一直为风湿病专家所提倡，但大多数痛风患者。 病例出现在初级保健中，许多风湿病学家担心痛风的初级保健管理 不够积极，启动 ULT 的阈值太高，并且使用的 ULT 剂量不足以实现 痛风治疗不足可能会因频繁发作而导致患者功能受损 伴有关节损伤的慢性痛风石性关节病 然而，治疗痛风的 TTT-SU 方法在很大程度上是有效的。 基于病理生理学原理，而不是美国最近的系统评价。 美国医师学会 (ACP) 临床指南委员会确认了抗炎药的有效性 治疗痛风发作的药物，以及 ULT 对于降低急性发作风险的有效性，但承认， “尚未测试达到特定目标水平的治疗”和“......我们仍然不确定治疗的价值 - 目标策略与基于最小化症状的治疗强度策略的比较。” 痛风管理指南既没有推荐启动 ULT 的具体阈值，也没有推荐具体的 SU 风湿病学界对 ACP 指南反应消极，主要关注点是。 因为它可能会恶化初级保健中已经不理想的痛风治疗。 为了解决争议，我们于 2018 年春季在波士顿召开了一次由 NIH 资助的会议，主要利益相关者也参加了会议 本次会议的共识是对痛风治疗策略进行比较有效性试验。 因此，管理将以循证的方式解决争议的最佳方式。 总体目标是设计一项试验，填补关键证据空白并直接为当前实践提供信息。 申请时，我们建议计划这样的试验的目的如下： 1) 进行 Delphi 小组流程以确定 2）准备试验细节，包括U01提案 （将在规划期的第二年提交）以及研究方案、培训文件、 操作程序手册、同意书和研究者手册，并进行模拟招募。

项目成果

Designing a Strategy Trial for the Management of Gout: The Use of a Modified Delphi Panel.

设计痛风管理策略试验：使用改良的德尔菲面板。

• 发表时间: 2021-05
• 影响因子: 3.4
• 作者: Solomon, Daniel H;Weissman, Joel S;Choi, Hyon;Atlas, Steven J;Berardinelli, Cesar;Dedier, Julien;Fischer, Michael A;Fitzgerald, John;Hinteregger, Erica;Johnsen, Brianne;Marini, Diana D;McLean, Robert;Murray, Fred;Neogi, Tuhina;Oertel, Lynn B
• 通讯作者: Oertel, Lynn B