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

Tatsuo Hosoya, Kenjiro Kimura, Sadayoshi Itoh, Masaaki Inaba, Shunya Uchida, Yasuhiko Tomino, Hirofumi Makino, Seiichi Matsuo, Tetsuya Yamamoto, Iwao Ohno, Yugo Shibagaki, Satoshi Iimuro, Naohiko Imai, Masanari Kuwabara, Hiroshi Hayakawa

Research output: Contribution to journalArticle

46 Citations (Scopus)

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/Design: 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.Discussion: 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.Trial registration: UMIN Identifier: UMIN000008343.

Original languageEnglish
Article number26
JournalTrials
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 16 2014

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Hyperuricemia
Gout
Uric Acid
Chronic Renal Insufficiency
Kidney
Tablets
Serum
Glomerular Filtration Rate
Gouty Arthritis
Placebos
Drug Therapy
Randomized Controlled Trials
Xanthine Oxidase
Febuxostat
Life Style
Japan
Control Groups
Incidence
Research
Pharmaceutical Preparations

Keywords

  • Chronic kidney disease
  • Hyperuricemia
  • Placebo
  • Randomized controlled study
  • Reduced renal function
  • Urate-lowering therapy
  • Xanthine oxidase inhibitor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

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. / Hosoya, Tatsuo; Kimura, Kenjiro; Itoh, Sadayoshi; Inaba, Masaaki; Uchida, Shunya; Tomino, Yasuhiko; Makino, Hirofumi; Matsuo, Seiichi; Yamamoto, Tetsuya; Ohno, Iwao; Shibagaki, Yugo; Iimuro, Satoshi; Imai, Naohiko; Kuwabara, Masanari; Hayakawa, Hiroshi.

In: Trials, Vol. 15, No. 1, 26, 16.01.2014.

Research output: Contribution to journalArticle

Hosoya, Tatsuo ; Kimura, Kenjiro ; Itoh, Sadayoshi ; Inaba, Masaaki ; Uchida, Shunya ; Tomino, Yasuhiko ; Makino, Hirofumi ; Matsuo, Seiichi ; Yamamoto, Tetsuya ; Ohno, Iwao ; Shibagaki, Yugo ; Iimuro, Satoshi ; Imai, Naohiko ; Kuwabara, Masanari ; Hayakawa, Hiroshi. / 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. In: Trials. 2014 ; Vol. 15, No. 1.
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T2 - Study protocol for a multicenter randomized controlled study

AU - Hosoya, Tatsuo

AU - Kimura, Kenjiro

AU - Itoh, Sadayoshi

AU - Inaba, Masaaki

AU - Uchida, Shunya

AU - Tomino, Yasuhiko

AU - Makino, Hirofumi

AU - Matsuo, Seiichi

AU - Yamamoto, Tetsuya

AU - Ohno, Iwao

AU - Shibagaki, Yugo

AU - Iimuro, Satoshi

AU - Imai, Naohiko

AU - Kuwabara, Masanari

AU - Hayakawa, Hiroshi

PY - 2014/1/16

Y1 - 2014/1/16

N2 - 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/Design: 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.Discussion: 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.Trial registration: UMIN Identifier: UMIN000008343.

AB - 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/Design: 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.Discussion: 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.Trial registration: UMIN Identifier: UMIN000008343.

KW - Chronic kidney disease

KW - Hyperuricemia

KW - Placebo

KW - Randomized controlled study

KW - Reduced renal function

KW - Urate-lowering therapy

KW - Xanthine oxidase inhibitor

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