Sakuma Masashi, Toyoda Shigeru, Arikawa Takuo, Koyabu Yota, Kato Toru, Adachi Taichi, Suwa Hideaki, Narita Jun-Ichi, Anraku Koetsu, Ishimura Kimihiko, Yamauchi Fumitake, Sato Yasunori, Inoue Teruo
Department of Cardiovascular Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.
Department of Clinical Research, National Hospital Organization Tochigi Medical Center, Utsunomiya, Japan.
Clin Exp Nephrol. 2018 Dec;22(6):1379-1386. doi: 10.1007/s10157-018-1599-6. Epub 2018 Jun 18.
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.
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.
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.
高尿酸血症与包括心力衰竭在内的心血管疾病密切相关。然而，黄嘌呤氧化酶抑制对慢性心力衰竭患者是否有益仍存在争议。我们设计了黄嘌呤氧化酶抑制剂在合并高尿酸血症的慢性心力衰竭患者中的疗效研究（Excited-UA研究），以比较新型黄嘌呤氧化还原酶抑制剂托匹司他与传统药物别嘌醇对慢性心力衰竭合并高尿酸血症患者的有益作用。我们关注血清N末端脑钠肽前体（NT-proBNP）水平、基于超声心动图的心脏功能、血管内皮功能、肾功能、炎症和氧化应激。
Excited-UA是一项前瞻性、随机、开放标签、盲终点临床试验，旨在证明我们的假设，即托匹司他在慢性心力衰竭合并高尿酸血症患者中比别嘌醇更有效。总共140例慢性心力衰竭合并高尿酸血症患者（血浆脑钠肽水平≥40 pg/mL且血清尿酸水平≥7.0 mg/dL）被随机分配（比例1:1）至托匹司他组（40 - 160 mg/天）或别嘌醇组（100 - 300 mg/天），以达到目标尿酸水平6.0 mg/dL。根据方案，所有患者每年随访24周。主要终点是24周时血清NT-proBNP水平相对于基线的变化百分比。
Excited-UA研究将为黄嘌呤氧化还原酶抑制剂治疗慢性心力衰竭合并高尿酸血症患者的临床相关性提供新的证据。
