The effects of xanthine oxidase inhibitor in patients with chronic heart failure complicated with hyperuricemia: a prospective randomized controlled clinical trial of topiroxostat vs allopurinol-study protocol

Clin Exp Nephrol. 2018 Dec;22(6):1379-1386. doi: 10.1007/s10157-018-1599-6. Epub 2018 Jun 18.


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.

Keywords: Allopurinol; Chronic heart failure; Hyperuricemia; N-terminal pro-brain natriuretic peptide (NT-proBNP); Topiroxostat; Xanthine oxidase inhibitor.

Publication types

  • Clinical Trial Protocol
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allopurinol / therapeutic use*
  • Chronic Disease
  • Echocardiography
  • Enzyme Inhibitors / therapeutic use*
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Humans
  • Hyperuricemia / blood
  • Hyperuricemia / complications
  • Hyperuricemia / drug therapy*
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Nitriles / therapeutic use*
  • Peptide Fragments / blood
  • Pyridines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Research Design
  • Xanthine Oxidase / antagonists & inhibitors*
  • Young Adult


  • Enzyme Inhibitors
  • Nitriles
  • Peptide Fragments
  • Pyridines
  • pro-brain natriuretic peptide (1-76)
  • FYX-051
  • Natriuretic Peptide, Brain
  • Allopurinol
  • Xanthine Oxidase