Masashi Sakuma1, Shigeru Toyoda1, Takuo Arikawa1, Yota Koyabu1, Toru Kato2, Taichi Adachi3, Hideaki Suwa3, Jun-Ichi Narita4, Koetsu Anraku5, Kimihiko Ishimura5, Fumitake Yamauchi6, Yasunori Sato7, Teruo Inoue8. 1. Department of Cardiovascular Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan. 2. Department of Clinical Research, National Hospital Organization Tochigi Medical Center, Utsunomiya, Japan. 3. Department of Cardiology, National Hospital Organization Tochigi Medical Center, Utsunomiya, Japan. 4. Department of Neurosurgery, Tochigi Medical Center Tochinoki, Tochigi, Japan. 5. Department of Internal Medicine, Tochigi Medical Center Tochinoki, Tochigi, Japan. 6. Department of Cardiology, Yuai Memorial Hospital, Koga, Japan. 7. Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan. 8. Department of Cardiovascular Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan. inouet@dokkyomed.ac.jp.
Abstract
BACKGROUND: Hyperuricemia has a close relationship with cardiovascular diseases including heart failure. However, it is controversial whether xanthine oxidase inhibition has benefits for patients with chronic heart failure. We designed the Effect of Xanthine Oxidase Inhibitor in Chronic Heart Failure Patients Complicated with Hyperuricemia study (Excited-UA study) to compare the beneficial effects between a novel xanthine oxidoreductase inhibitor, topiroxostat, and a conventional agent, allopurinol, in patients with chronic heart failure and hyperuricemia. We focus on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiography-based cardiac function, vascular endothelial function, renal function, inflammation, and oxidative stress. METHODS: The excited-UA is a prospective, randomized, open-label, blinded-endpoint clinical trial designed to prove our hypothesis that topiroxostat is more effective than allopurinol in patients with chronic heart failure and hyperuricemia. A total of 140 patients with chronic heart failure and hyperuricemia (plasma brain natriuretic peptide level ≥ 40 pg/mL and serum uric acid level ≥ 7.0 mg/dL) are randomly assigned (ratio 1:1) into either the topiroxostat group (40-160 mg/day) or allopurinol group (100-300 mg/day), to achieve the target uric acid level of 6.0 mg/dL. According to the protocol, all patients are followed up annually for 24 weeks. The primary endpoint is percent change in serum NT-proBNP level at 24 weeks from baseline. CONCLUSIONS: The Excited-UA study would provide novel evidence for the clinical relevancy of xanthine oxidoreductase inhibitor treatment in patients with chronic heart failure and hyperuricemia.
RCT Entities:
BACKGROUND:Hyperuricemia has a close relationship with cardiovascular diseases including heart failure. However, it is controversial whether xanthine oxidase inhibition has benefits for patients with chronic heart failure. We designed the Effect of Xanthine Oxidase Inhibitor in Chronic Heart FailurePatients Complicated with Hyperuricemia study (Excited-UA study) to compare the beneficial effects between a novel xanthine oxidoreductase inhibitor, topiroxostat, and a conventional agent, allopurinol, in patients with chronic heart failure and hyperuricemia. We focus on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiography-based cardiac function, vascular endothelial function, renal function, inflammation, and oxidative stress. METHODS: The excited-UA is a prospective, randomized, open-label, blinded-endpoint clinical trial designed to prove our hypothesis that topiroxostat is more effective than allopurinol in patients with chronic heart failure and hyperuricemia. A total of 140 patients with chronic heart failure and hyperuricemia (plasma brain natriuretic peptide level ≥ 40 pg/mL and serum uric acid level ≥ 7.0 mg/dL) are randomly assigned (ratio 1:1) into either the topiroxostat group (40-160 mg/day) or allopurinol group (100-300 mg/day), to achieve the target uric acid level of 6.0 mg/dL. According to the protocol, all patients are followed up annually for 24 weeks. The primary endpoint is percent change in serum NT-proBNP level at 24 weeks from baseline. CONCLUSIONS: The Excited-UA study would provide novel evidence for the clinical relevancy of xanthine oxidoreductase inhibitor treatment in patients with chronic heart failure and hyperuricemia.
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