S Timilsina1, K Brittan1, J R O'Dell1, M Brophy2, A Davis-Karim3, A M Henrie3, T Neogi4, J Newcomb1, P M Palevsky5, M H Pillinger6, D Pittman3, T H Taylor7, H Wu2, T R Mikuls8. 1. VA Nebraska-Western Iowa Health Care System, Omaha, NE, United States; University of Nebraska Medical Center, Omaha, NE, United States. 2. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Cooperative Study Program Coordinating Center, Boston, MA, United States. 3. VA Cooperative Study Program, Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, United States. 4. Boston University School of Medicine, Boston, MA, United States. 5. VA Pittsburgh Healthcare System, Pittsburgh, PA, United States. 6. New York University Langone Medical Center, New York, NY, United States. 7. White River Junction VA Hospital, White River Junction, VT, United States. 8. VA Nebraska-Western Iowa Health Care System, Omaha, NE, United States; University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: Ted.Mikuls@va.gov.
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. Published by Elsevier Inc.
RCT Entities:
BACKGROUND:Goutpatients 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 goutpatients 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. Published by Elsevier Inc.
Authors: James R O'Dell; Mary T Brophy; Michael H Pillinger; Tuhina Neogi; Paul M Palevsky; Hongsheng Wu; Anne Davis-Karim; Jeff A Newcomb; Ryan Ferguson; David Pittman; Grant W Cannon; Thomas Taylor; Robert Terkeltaub; Amy C Cannella; Bryant R England; Lindsay N Helget; Ted R Mikuls Journal: NEJM Evid Date: 2022-02-03
Authors: Nada Elmagboul; Brian W Coburn; Jeffrey Foster; Amy Mudano; Joshua Melnick; Debra Bergman; Shuo Yang; David Redden; Lang Chen; Cooper Filby; Jeffrey R Curtis; Ted R Mikuls; Kenneth G Saag Journal: Arthritis Res Ther Date: 2019-06-29 Impact factor: 5.156
Authors: Huai Leng Pisaniello; Mark C Fisher; Hamish Farquhar; Ana Beatriz Vargas-Santos; Catherine L Hill; Lisa K Stamp; Angelo L Gaffo Journal: Arthritis Res Ther Date: 2021-04-28 Impact factor: 5.156
Authors: Lisa K Stamp; Hamish Farquhar; Huai Leng Pisaniello; Ana B Vargas-Santos; Mark Fisher; David B Mount; Hyon K Choi; Robert Terkeltaub; Catherine L Hill; Angelo L Gaffo Journal: Nat Rev Rheumatol Date: 2021-07-30 Impact factor: 20.543