Design and Rationale for the Veterans Affairs "Cooperative Study Program 594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat" Trial

Contemp Clin Trials. 2018 May;68:102-108. doi: 10.1016/j.cct.2018.03.015. Epub 2018 Mar 27.


Background: 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.

Methods: 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.

Conclusion: 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.

Trial registration: NCT02579096.

Keywords: Allopurinol; Febuxostat; Gout; Randomized controlled trial; Urate lowering therapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Allopurinol* / administration & dosage
  • Allopurinol* / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Dosage Calculations*
  • Drug Monitoring / methods
  • Febuxostat* / administration & dosage
  • Febuxostat* / adverse effects
  • Gout Suppressants / administration & dosage
  • Gout Suppressants / adverse effects
  • Gout* / blood
  • Gout* / drug therapy
  • Humans
  • Male
  • Medication Therapy Management / standards
  • Middle Aged
  • Practice Guidelines as Topic
  • Treatment Outcome
  • United States
  • United States Department of Veterans Affairs
  • Uric Acid / blood
  • Veterans Health*


  • Gout Suppressants
  • Febuxostat
  • Uric Acid
  • Allopurinol

Associated data