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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 Hosoya1*, Kenjiro Kimura2, Sadayoshi Itoh3, Masaaki Inaba4, Shunya Uchida5, Yasuhiko Tomino6, Hirofumi Makino7, Seiichi Matsuo8, Tetsuya Yamamoto9, Iwao Ohno1, Yugo Shibagaki2, Satoshi Iimuro10, Naohiko Imai2, Masanari Kuwabara11 and Hiroshi Hayakawa1

Author Affiliations

1 Division of Nephrology and Hypertension, the Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan

2 St. Marianna University School of Medicine, Kanagawa, Japan

3 Tohoku University School of Medicine, Miyagi, Japan

4 Osaka City University School of Medicine, Osaka, Japan

5 Teikyo University School of Medicine, Tokyo, Japan

6 Juntendo University School of Medicine, Tokyo, Japan

7 Okayama University School of Medicine, Okayama, Japan

8 Nagoya University School of Medicine, Aichi, Japan

9 Hyogo college of Medicine, Hyogo, Japan

10 The University of Tokyo Hospital, Clinical Research Support Center, Tokyo, Japan

11 Toranomon Hospital, Tokyo, Japan

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Trials 2014, 15:26  doi:10.1186/1745-6215-15-26

Published: 16 January 2014

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

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