CSP594 Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat
Condition: Gout; Chronic Kidney Diseases
MeSH terms: Gout; Kidney Diseases; Renal Insufficiency, Chronic
Intervention: allopurinol capsule, 100-800 mg by mouth once daily; febuxostat tablet 40-120 mg by mouth once daily; Placebo, vehicle control (febuxostat-shaped); Placebo, vehicle control (allopurinol-shaped)
Intervention description: Patients will be up-titrated up to the dose required to reach target uric acid levels.; Patients will be up-titrated to the dose required to reach target uric acid levels.; Placebo tablets resembling febuxostat will be given with allopurinol.; Placebo capsules resembling allopurinol will be given with febuxostat.
Intervention MeSH terms: Allopurinol; Febuxostat
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 950.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gout; Allopurinol; Febuxostat; CKD

Summary:

      This trial will compare two effective therapies, allopurinol and febuxostat, to lower serum
      uric acid and therefore prevent further gout attacks. These therapies have never been
      compared at appropriate doses. Further, they will be studied in patients with kidney disease
      for the first time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 years

          -  History of gout - crystal proven or historical as defined by ACR criteria listed above

          -  Serum urate level > 6.8 mg/dl

        Exclusion Criteria:

          -  Stage 4 or 5 Chronic Kidney Disease (CKD) - defined as eGFR < 30 ml/min/1.73 m2

          -  Women less than 50 years of age

          -  Patients with a history of prior solid organ / hematopoietic transplantation

          -  Previous allergy or intolerance to allopurinol or febuxostat

          -  Patients who are not candidates for any of the recommended prophylactic medications
             (colchicine, naprosyn or glucocorticoids)

          -  Patients who in the opinion of the investigator have a high genetic risk for
             allopurinol hypersensitivity syndrome (AHS*) unless they have been found to be
             negative for HLA B5801.

          -  Previous history of failure to reach target uric acid levels despite therapy with
             allopurinol at dose > 300 mg/day

          -  Prior febuxostat use

          -  Patients with malignancies that are currently active with exception of non-melanoma
             skin cancer

          -  Patients with serum uric acid levels >15 mg/dl

          -  Patients with myelodysplasia and hemoglobin of < 8.5 mg/dL

          -  Patients with chronic liver disease with more than one of the following:

               -  INR > 1.7, not on Warfarin therapy

               -  Bilirubin 2 mg/dL

               -  Serum albumin < 3.5 mg/dL

               -  Ascites

               -  Encephalopathy

          -  Current use of azathioprine, mercaptopurine, didanosine, cyclophosphamide, probenecid,
             lesinurad or pegloticase

          -  Enrollment in another randomized interventional clinical trial

          -  Any severe medical condition that, in the enrolleer's opinion, is likely to compromise
             the participant's ability to complete the trial