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

S. Timilsina, K. Brittan, James Robert O'Dell, M. Brophy, A. Davis-Karim, A. M. Henrie, T. Neogi, J. Newcomb, P. M. Palevsky, M. H. Pillinger, D. Pittman, T. H. Taylor, H. Wu, Ted R Mikuls

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)102-108
Number of pages7
JournalContemporary Clinical Trials
Volume68
DOIs
StatePublished - May 2018

Fingerprint

Allopurinol
Gout
Veterans
Uric Acid
Xanthine Oxidase
Febuxostat
Therapeutics
Outcome Assessment (Health Care)
Guidelines
Health
Serum

Keywords

  • Allopurinol
  • Febuxostat
  • Gout
  • Randomized controlled trial
  • Urate lowering therapy

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Design and Rationale for the Veterans Affairs “Cooperative Study Program 594 Comparative Effectiveness in Gout : Allopurinol vs. Febuxostat” Trial. / Timilsina, S.; Brittan, K.; O'Dell, James Robert; 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, Ted R.

In: Contemporary Clinical Trials, Vol. 68, 05.2018, p. 102-108.

Research output: Contribution to journalArticle

Timilsina, S, Brittan, K, O'Dell, JR, Brophy, M, Davis-Karim, A, Henrie, AM, Neogi, T, Newcomb, J, Palevsky, PM, Pillinger, MH, Pittman, D, Taylor, TH, Wu, H & Mikuls, TR 2018, 'Design and Rationale for the Veterans Affairs “Cooperative Study Program 594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat” Trial', Contemporary Clinical Trials, vol. 68, pp. 102-108. https://doi.org/10.1016/j.cct.2018.03.015
Timilsina, S. ; Brittan, K. ; O'Dell, James Robert ; 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, Ted R. / Design and Rationale for the Veterans Affairs “Cooperative Study Program 594 Comparative Effectiveness in Gout : Allopurinol vs. Febuxostat” Trial. In: Contemporary Clinical Trials. 2018 ; Vol. 68. pp. 102-108.
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abstract = "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.",
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AU - O'Dell, James Robert

AU - Brophy, M.

AU - Davis-Karim, A.

AU - Henrie, A. M.

AU - Neogi, T.

AU - Newcomb, J.

AU - Palevsky, P. M.

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