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

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.

Eligibility

* Inclusion Criteria:

  1. Adult gout patients aged ≥19 but \<80 years.
  2. 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.
  3. 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
  4. Patients without palpable or visible tophi on physical examination (evaluated at pre-defined 18 joint sites and the ears).
  5. Patients without acute gouty attack or history of nephrolithiasis in the past 12 months
  6. Patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m² or higher, based on the Cockcroft-Gault formula.
  7. Patients who voluntarily provide written informed consent to participate.
* Exclusion Criteria:

  1. Subjects who continuously require prophylactic low-dose colchicine/NSAIDs.
  2. 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.
  3. 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.
  4. 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
  5. Subjects with a history of hypersensitivity to febuxostat or allopurinol
  6. Subjects with unstable cardiovascular conditions, who require adjustment of urgent their therapy
  7. Subjects taking mercaptopurine or azathioprine
  8. Subjects with genetic issues such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  9. Subjects with moderate or severe liver dysfunction (AST or ALT levels greater than 3 times the upper normal limit)
  10. 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.

Conditions3

Interventions1

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