title: The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study.
abstract: BACKGROUND
  Hyperuricemia is a risk factor for the onset of chronic kidney disease (CKD) and is significantly associated with the progression of CKD. However, there is no sufficient evidence by interventional research supporting a cause-effect relationship. Hyperuricemic patients without gouty arthritis, whose serum urate (SUA) concentration is ≥8.0 mg/dL and who have a complication, are treated by pharmacotherapy in addition to lifestyle guidance. Nevertheless, there is no evidence that rationalizes pharmacotherapy for patients with hyperuricemia who have no complication and whose SUA concentration is below 9.0 mg/dL.
  
  
  METHODS
  The FEATHER (FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3) study is a prospective, multicenter, double-blind, randomized, placebo-controlled trial of febuxostat-a novel, nonpurine, selective, xanthine oxidase inhibitor. The present study will enroll, at 64 medical institutions in Japan, 400 Japanese patients aged 20 years or older who have hyperuricemia without gouty arthritis, who present CKD stage 3, and whose SUA concentration is 7.1-10.0 mg/dL. Patients are randomly assigned to either the febuxostat or the control group, in which febuxostat tablets and placebo are administered orally, respectively. The dosage of the study drugs should be one 10-mg tablet/day at weeks 1 to 4 after study initiation, increased to one 20-mg tablet/day at weeks 5 to 8, and elevated to one 40-mg tablet/day at week 9 and then maintained until week 108. The primary endpoint is estimated glomerular filtration rate (eGFR) slope. The secondary endpoints include the amount and percent rate of change in eGFR from baseline to week 108, the amount and percent rate of change in SUA concentration from baseline to week 108, the proportion of patients who achieved an SUA concentration≤6.0 mg/dL, and the incidence of renal function deterioration.
  
  
  CONCLUSIONS
  The present study aims to examine whether febuxostat prevents a further reduction in renal function as assessed with eGFR in subjects and will (1) provide evidence to indicate the inverse association between a reduction in SUA concentration and an improvement in renal function and (2) rationalize pharmacotherapy for subjects and clarify its clinical relevance.
  
  
  BACKGROUND
  UMIN Identifier: UMIN000008343.
authors.affiliation: Division of Nephrology and Hypertension, the Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan. t-hosoya@jikei.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Itoh
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohno
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shibagaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iimuro
authors.forename: Naohiko
authors.initials: N
authors.lastname: Imai
authors.forename: Masanari
authors.initials: M
authors.lastname: Kuwabara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
mesh_terms: D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000069465:Febuxostat; D005919:Glomerular Filtration Rate; D006074:Gout Suppressants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D007564:Japan; D007668:Kidney / Q000503:physiopathology*; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D012107:Research Design; D012307:Risk Factors; D012720:Severity of Illness Index; D013607:Tablets; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D013607:Tablets; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid