the Effects of Febuxostat Dose Tapering in Gout Patients Optimally Controlled for 5 Years or More

NCT06622603 | Recruiting Phase 4

• 1 other identifier: TARGET-V1-01
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare the changes in serum urate levels and symptom recurrence after reducing or suspending urate-lowering agents in well-controlled gout patients (the 'after dishes are clean' state in the Dirty Dish hypothesis) Researchers will compare three randomized groups: the reducing group takes febuxostat 20 mg once daily for 12 months, the discontinuing group takes a placebo once daily for 6 months, followed by febuxostat 20 mg once daily for the next 6 months, and the maintaining group continues their pre-study urate-lowering agents for 12 months, serving as an observational reference group. During the 12-month study period, participants will visit every 3 months for laboratory evaluations including serum urate levels, and for checking symptomatic status using questionnaires and diaries. Additionally, musculoskeletal ultrasonography and serum sample collection will be performed at baseline to study predictors for maintaining serum urate levels \<7.0 mg/dL after reducing or suspending urate-lowering therapy.

Conditions

Gout; Uric Acid

Keywords

Febuxostat; Allopurinol

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with serum urate levels <7.0 mg/dL

  The proportion of patients who maintain serum urate levels \<7.0 mg/dL at 6 months after taking febuxostat 20 mg once daily or after suspending urate-lowering agents

  6 months

Secondary Outcomes (9)

• The proportion of subjects with serum urate <7.0 mg/dL

  6 months and 12 months

• Serum urate levels

  6 months and 12 months

• Gout Impact Scale (GIS) score using the Korean version

  6 months and 12 months

• Patient's overall assessment of gout using a visual analog scale

  6 months and 12 months

• EuroQol(EQ)-5D score

  6 months and 12 months

Other Outcomes (1)

• The reliability of the ultrasound scoring system for tophi in gout patients

  Baseline

Study Arms (3)

Discontinuing group

PLACEBO COMPARATOR

The participants (n=15) will take a placebo once daily for 6 months, followed by febuxostat 20 mg once daily for the next 6 months. Randomization is stratified based on the urinary urate excretion rate (≤5.5% vs. \>5.5%).

Drug: Febuxostat

Reducing group

ACTIVE COMPARATOR

The participants (n=29) will take febuxostat 20 mg once daily for 12 months. Randomization is stratified based on the urinary urate excretion rate (≤5.5% vs. \>5.5%).

Drug: Febuxostat

Maintaining group

NO INTERVENTION

To serve as an observational reference group, The participants (n=15) will continue their urate-lowering agents for 12 months. Randomization is stratified based on the urinary urate excretion rate (≤5.5% vs. \>5.5%).

Interventions

Febuxostat DRUG

The minimal approved dose of febuxostat is 40 mg/day. We will use 0.5 tablet of febuxostat 40 mg or its placebo.

Also known as: Usoric® Tab 40mg

Discontinuing group; Reducing group

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult gout patients aged ≥19 but \<80 years.
• Gout patients treated with urate-lowering therapy (either allopurinol or febuxostat monotherapy, or a combination of two agents) for at least the past 5 years.
• Patients who have at least five serum urate level measurements over the past 5 years and meet one of the following criteria:
• All serum urate levels measured in the past 5 years have been maintained below 6.0 mg/dL; or the area under the curve (AUC) of serum urate levels over time for the past 5 years is less than 33.0 mg/dL x year
• Patients without palpable or visible tophi on physical examination (evaluated at pre-defined 18 joint sites and the ears).
• Patients without acute gouty attack or history of nephrolithiasis in the past 12 months
• Patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m² or higher, based on the Cockcroft-Gault formula.
• Patients who voluntarily provide written informed consent to participate.

You may not qualify if:

• Subjects who continuously require prophylactic low-dose colchicine/NSAIDs.
• Subjects already having taken low-dose urate-lowering agents. The low-dose urate-lowering agents are defined as allopurinol ≤200 mg/day or febuxostat ≤20 mg/day. But patients on a combination of low-dose allopurinol and febuxostat are eligible.
• Subjects taking medications that could affect serum uric acid levels and uric acid fractional excretion rates, such as benzbromarone, fenofibrate, loop diuretics, thiazide or thiazide-like diuretics, and losartan.
• Subjects classified as having high-risk alcohol use according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA):
• For men \<65 years: more than 14 drinks per week or for men ≥65 years or women: more than 7 drinks per week
• Subjects with a history of hypersensitivity to febuxostat or allopurinol
• Subjects with unstable cardiovascular conditions, who require adjustment of urgent their therapy
• Subjects taking mercaptopurine or azathioprine
• Subjects with genetic issues such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• Subjects with moderate or severe liver dysfunction (AST or ALT levels greater than 3 times the upper normal limit)
• Subjects for whom investigators anticipate that a change in a urate-lowering agent dose could present significant risks or that any factor could severely impact drug adherence, complicating study registration.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Gachon University Gil Medical Center: collaborator
• SMG-SNU Boramae Medical Center: collaborator
• Chungnam National University Hospital: collaborator
• Seoul National University Bundang Hospital: collaborator
• Ajou University Medical Center: collaborator
• Uijeongbu Eulji University Hospital: collaborator

Study Sites (1)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

RECRUITING

Related Publications (20)

• Dalbeth N, Phipps-Green A, Frampton C, Neogi T, Taylor WJ, Merriman TR. Relationship between serum urate concentration and clinically evident incident gout: an individual participant data analysis. Ann Rheum Dis. 2018 Jul;77(7):1048-1052. doi: 10.1136/annrheumdis-2017-212288. Epub 2018 Feb 20.

  PMID: 29463518 BACKGROUND

• Robinson PC, Frampton C, Phipps-Green A, Neogi T, Stamp L, Taylor W, Merriman TR, Dalbeth N. Longitudinal development of incident gout from low-normal baseline serum urate concentrations: individual participant data analysis. BMC Rheumatol. 2021 Aug 28;5(1):33. doi: 10.1186/s41927-021-00204-4.

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• FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, Gelber AC, Harrold LR, Khanna D, King C, Levy G, Libbey C, Mount D, Pillinger MH, Rosenthal A, Singh JA, Sims JE, Smith BJ, Wenger NS, Bae SS, Danve A, Khanna PP, Kim SC, Lenert A, Poon S, Qasim A, Sehra ST, Sharma TSK, Toprover M, Turgunbaev M, Zeng L, Zhang MA, Turner AS, Neogi T. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020 Jun;72(6):744-760. doi: 10.1002/acr.24180. Epub 2020 May 11. Erratum In: Arthritis Care Res (Hoboken). 2020 Aug;72(8):1187. doi: 10.1002/acr.24401. Arthritis Care Res (Hoboken). 2021 Mar;73(3):458. doi: 10.1002/acr.24566.

  PMID: 32391934 BACKGROUND

• Scheepers LEJM, van Onna M, Stehouwer CDA, Singh JA, Arts ICW, Boonen A. Medication adherence among patients with gout: A systematic review and meta-analysis. Semin Arthritis Rheum. 2018 Apr;47(5):689-702. doi: 10.1016/j.semarthrit.2017.09.007. Epub 2017 Oct 7.

  PMID: 29198878 BACKGROUND

• Kim A, Kim Y, Kim GT, Ahn E, So MW, Lee SG. Comparison of persistence rates between allopurinol and febuxostat as first-line urate-lowering therapy in patients with gout: an 8-year retrospective cohort study. Clin Rheumatol. 2020 Dec;39(12):3769-3776. doi: 10.1007/s10067-020-05161-w. Epub 2020 May 26.

  PMID: 32458236 BACKGROUND

• Perez-Ruiz F, Herrero-Beites AM, Carmona L. A two-stage approach to the treatment of hyperuricemia in gout: the "dirty dish" hypothesis. Arthritis Rheum. 2011 Dec;63(12):4002-6. doi: 10.1002/art.30649.

  PMID: 21898351 BACKGROUND

• Loebl WY, Scott JT. Withdrawal of allopurinol in patients with gout. Ann Rheum Dis. 1974 Jul;33(4):304-7. doi: 10.1136/ard.33.4.304. No abstract available.

  PMID: 4416909 BACKGROUND

• Perez-Ruiz F, Atxotegi J, Hernando I, Calabozo M, Nolla JM. Using serum urate levels to determine the period free of gouty symptoms after withdrawal of long-term urate-lowering therapy: a prospective study. Arthritis Rheum. 2006 Oct 15;55(5):786-90. doi: 10.1002/art.22232.

  PMID: 17013833 BACKGROUND

• Komoriya K, Hoshide S, Takeda K, Kobayashi H, Kubo J, Tsuchimoto M, Nakachi T, Yamanaka H, Kamatani N. Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1119-22. doi: 10.1081/NCN-200027381.

  PMID: 15571213 BACKGROUND

• Kamatani N, Fujimori S, Hada T, Hosoya T, Kohri K, Nakamura T, Ueda T, Yamamoto T, Yamanaka H, Matsuzawa Y. Placebo-controlled, double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study. J Clin Rheumatol. 2011 Jun;17(4 Suppl 2):S19-26. doi: 10.1097/RHU.0b013e31821d36de. Erratum In: J Clin Rheumatol. 2014 Sep;20(6):E1. Naoyuki, Kamatani [corrected to Kamatani, Naoyuki]; Shin, Fujimori [corrected to Fujimori, Shin]; Toshikazu, Hada [corrected to Hada, Toshikazu]; Tatsuo, Hosoya [corrected to Hosoya, Tatsuo]; Kenjiro, Kohri [corrected to Kohri, Kenjiro]; Toshitaka, Nakamur.

  PMID: 21654266 BACKGROUND

• Liang N, Sun M, Sun R, Xu T, Cui L, Wang C, Ma L, Cheng X, Xue X, Sun W, Yuan X, Zhang H, Li H, He Y, Ji A, Wu X, Li C. Baseline urate level and renal function predict outcomes of urate-lowering therapy using low doses of febuxostat and benzbromarone: a prospective, randomized controlled study in a Chinese primary gout cohort. Arthritis Res Ther. 2019 Sep 2;21(1):200. doi: 10.1186/s13075-019-1976-x.

  PMID: 31477161 BACKGROUND

• Yan F, Xue X, Lu J, Dalbeth N, Qi H, Yu Q, Wang C, Sun M, Cui L, Liu Z, He Y, Yuan X, Chen Y, Cheng X, Ma L, Li H, Ji A, Hu S, Ran Z, Terkeltaub R, Li C. Superiority of Low-Dose Benzbromarone to Low-Dose Febuxostat in a Prospective, Randomized Comparative Effectiveness Trial in Gout Patients With Renal Uric Acid Underexcretion. Arthritis Rheumatol. 2022 Dec;74(12):2015-2023. doi: 10.1002/art.42266. Epub 2022 Nov 11.

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• Morillon MB, Christensen R, Singh JA, Dalbeth N, Saag K, Taylor WJ, Neogi T, Kennedy MA, Pedersen BM, McCarthy GM, Shea B, Diaz-Torne C, Tedeschi SK, Grainger R, Abhishek A, Gaffo A, Nielsen SM, Noerup A, Simon LS, Lassere M, Tugwell P, Stamp LK, Gout Working Group FTO. Serum urate as a proposed surrogate outcome measure in gout trials: From the OMERACT working group. Semin Arthritis Rheum. 2021 Dec;51(6):1378-1385. doi: 10.1016/j.semarthrit.2021.11.004. Epub 2021 Nov 15.

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• Khosravan R, Grabowski BA, Wu JT, Joseph-Ridge N, Vernillet L. Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine selective inhibitor of xanthine oxidase, in a dose escalation study in healthy subjects. Clin Pharmacokinet. 2006;45(8):821-41. doi: 10.2165/00003088-200645080-00005.

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Related Links

• Gout: diagnosis and management \| Guidance - NICE

MeSH Terms

Conditions

Gout

Interventions

Febuxostat

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yun Jong Lee, MD, PhD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yun Jong Lee, MD, PhD

CONTACT

82317877051; yn35@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: October 2, 2024
• Study Start: September 10, 2025
• Primary Completion (Estimated): February 19, 2027
• Study Completion (Estimated): August 19, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)