Oyama, Jun‑ichi Saga University
Tanaka, Atsushi Saga University
Sato, Yasunori Chiba University
Tomiyama, Hirofumi Tokyo Medical University
Ishizu, Tomoko University of Tsukuba
Taguchi, Isao Dokkyo Medical University
Kuroyanagi, Takanori Dokkyo Medical University
Teragawa, Hiroki Hiroshima General Hospital of West Japan Railway Company
Ishizaka, Nobukazu Osaka Medical College
Kanzaki, Yumiko Osaka Medical College
Ohishi, Mitsuru Kagoshima University
Eguchi, Kazuo Jichi Medical University
Higashi, Yukihito Hiroshima University
Maemura, Koji Nagasaki University
Ako, Junya Kitasato University
Bando, Yasuko K. Nagoya University
Ueda, Shinichiro University of the Ryukyus
Inoue, Teruo Dokkyo Medical University
Murohara, Toyoaki Nagoya University
Node, Koichi Saga University
Intima-media thickness (IMT)
Randomized controlled trial
Xanthine oxidase inhibitor
Background: Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia.
Methods: The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness ≥1.1 mm will be randomized centrally to receive either febuxostat (10–60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, ≥65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, ≥8.0 mg/dL), and carotid intima-media thickness (<1.3, ≥1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging.
Conclusions: PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia.
Springer Nature|BioMed Central
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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