Intensive uric acid-lowering therapy in CKD patients: the protocol for a randomized controlled trial
Hyperuricemia would be a risk factor for the development/progression of CKD. However, several studies showed U-shape association between serum uric acid level and renal impairment, suggesting that hypouricemia was rather associated with renal dysfunction. Perhaps, there is the optimal target level of serum UA for renal function.
The Target-UA study is a multicenter randomized controlled trial. Eligible CKD patients (eGFR ≥ 30, < 60 mL/min/1.73 m2 and urine protein < 0.5 g/gCr or urine albumin to creatinine ratio (ACR) < 300 mg/gCr) with serum UA ≥ 8.0 mg/dL (≥ 7.0 mg/dl: under the treatment) will be enrolled and be randomly assigned to the intensive therapy group (target serum UA level ≥ 4.0 mg/dL, < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL, < 7.0 mg/dL). Topiroxostat, a new xanthine oxidase inhibitor, will be administered to treat hyperuricemia. The primary endpoint is a change in logarithmic value of urine ACR between baseline and week 52 of treatment. The secondary endpoints include changes in serum UA, eGFR, urine protein, lipid profile, and onset of composite cardiovascular events, renal events, gouty arthritis, and attack of urolithiasis. The number of subjects has been set to be 185 in each group for a total of 370.
This is the first study, to the best of our knowledge, to determine the optimal target level of serum UA for renal protection and is expected to lead to progress in CKD treatment.
(UMIN000026741 and jRCTs051180146).
KeywordsAlbuminuria Chronic kidney disease Topiroxostat Uric acid
This study is funded by Fuji Yakuhin Co., Ltd.
Compliance with ethical standards
Conflict of interest
MK is a consultant for Reason Why Inc. and has received honoraria from KYORIN Pharmaceutical Co.,Ltd., and has received grants from DAIICHI SANKYO COMPANY, LIMITED, Mitsubishi Tanabe Pharma Corporation, and FUJI YAKUHIN CO., LTD. SH has received honoraria from Mitsubishi Tanabe Pharma Corporation, Bayer Holding Ltd., MSD K.K., and Takeda Pharmaceutical Company Limited. YS is a consultant for Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., and Mitsubishi Tanabe Pharma Corporation, and has received honoraria from Otsuka Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, DAIICHI SANKYO COMPANY, LIMITED, Siemens Healthcare Diagnostics K.K., MSD K.K., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Kowa Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, TEIJIN PHARMA LIMITED, Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Bayer Holding Ltd., Medtronic, Inc., MOCHIDA PHARMACEUTICAL CO., LTD., Novo Nordisk Pharma Ltd., and has received grants from Japan Society for the Promotion of Science, The Ministry of Health, Labour and Welfare Scientific Research, Japan Agency for Medical Research and Development Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, TEIJIN PHARMA LIMITED, Bayer Holding Ltd., DAIICHI SANKYO COMPANY, LIMITED, Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc., Sanofi K.K., Novartis Pharma K.K., MSD K.K., CHUGAI PHARMACEUTICAL CO., LTD., Kyowa Hakko Kirin Co., Ltd., Nihon Medi-Physics Co.,Ltd., ONO PHARMACEUTICAL CO., LTD., Eli Lilly Japan K.K., FUJI YAKUHIN CO., LTD., Sumitomo Dainippon Pharma Co., Ltd. HS has received consulting fee from Pfizer Japan Inc., and has received honoraria from FUJI YAKUHIN CO., LTD. TN lectured a graduate student who was an employee in FUJI YAKUHIN CO., LTD. for 2 years at Nara medical university, and has two patents regarding to hyperuricemia, and has stock for XORT Therapeutics, and has received grant from FUJI YAKUHIN CO., LTD. Remaining authors have declared that no conflict of interest exists.
The study was conducted in compliance with the Declaration of Helsinki and according to the Clinical Trials Act (Act No. 16 of April 14, 2017) in Japan. The study protocol was approved by the Nara Medical University Certified Review Board on February 22, 2019 (No. nara0008: CRB5180011). The study shall be started at each site after approval of the protocol by the Ethics Review Committee.
The investigators will give a sufficient explanation of the study using explanatory documents to each patient and written informed consent will be obtained from all individual participants included in the study before primary enrollment.
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