Timilsina S, Brittan K, O'Dell J R, Brophy M, Davis-Karim A, Henrie A M, Neogi T, Newcomb J, Palevsky P M, Pillinger M H, Pittman D, Taylor T H, Wu H, Mikuls T R
VA Nebraska-Western Iowa Health Care System, Omaha, NE, United States; University of Nebraska Medical Center, Omaha, NE, United States.
Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Cooperative Study Program Coordinating Center, Boston, MA, United States.
Contemp Clin Trials. 2018 May;68:102-108. doi: 10.1016/j.cct.2018.03.015. Epub 2018 Mar 27.
Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a "treat-to-target" strategy congruent with specialty guidelines.
We have planned and initiated the Veterans Affairs (VA) Cooperative Study Program (CSP) 594, Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study. This large double-blind, non-inferiority trial will enroll 950 gout patients randomized to receive allopurinol or febuxostat. Patients will be followed for a total of 72 weeks encompassing 3 distinct 24-week study phases. During Phase I (0-24 weeks), participants will undergo gradual dose titration of ULT until achievement of serum uric acid (sUA) <6.0 mg/dL or <5.0 mg/dL if tophi are present. Dose escalation will not be allowed during final three study visits of Phase 2 (24-48 weeks) and during Phase 3 (48-72 weeks). The primary study outcome is the proportion of participants experiencing at least one gout flare during Phase 3. Subsequent to the 72-week study, participants will be followed passively for up to 10 years after the study to assess long-term health outcomes.
With its completion, the VA Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study will demonstrate the central role of gradual ULT dose escalation and a treat-to-target strategy in gout management.
痛风患者通常无法获得最佳治疗效果，部分原因是降尿酸治疗（ULT）的给药方式欠佳，包括一线黄嘌呤氧化酶抑制剂别嘌醇或非布司他。非布司他获批前的研究将该药物与别嘌醇以不适当的低固定剂量进行了比较。我们将使用两种药物的适当滴定剂量以及符合专业指南的“达标治疗”策略，比较别嘌醇与非布司他在痛风治疗中的效果。
我们已规划并启动了退伍军人事务部（VA）合作研究项目（CSP）594，即痛风的比较疗效：别嘌醇与非布司他研究。这项大型双盲、非劣效性试验将招募950名痛风患者，随机分为接受别嘌醇或非布司他治疗组。患者将接受为期72周的随访，包括3个不同的24周研究阶段。在第一阶段（0 - 24周），参与者将接受ULT的逐步剂量滴定，直至血清尿酸（sUA）<6.0 mg/dL，若存在痛风石则降至<5.0 mg/dL。在第二阶段（24 - 48周）和第三阶段（48 - 72周）的最后三次研究访视期间，不允许增加剂量。主要研究结局是第三阶段至少经历一次痛风发作的参与者比例。在72周研究结束后，将对参与者进行长达10年的被动随访，以评估长期健康结局。
随着研究的完成，VA痛风的比较疗效：别嘌醇与非布司他研究将证明ULT剂量逐步增加和达标治疗策略在痛风管理中的核心作用。
