Rationale, design and organisation of an efficacy and safety study of oxypurinol added to standard therapy in patients with NYHA class III - IV congestive heart failure

Ronald S. Freudenberg, Richard P. Schwarz, Joanne Brown, Alan Moore, Douglas Mann, Michael M. Givertz, Wilson S. Colucci, Joshua Hare

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Oxypurinol, the active metabolite of allopurinol and a potent xanthine oxidase inhibitor (XOI), is under evaluation as a novel agent for the treatment of congestive heart failure (HF). Several lines of evidence provide the rationale for the hypothesis that XOIs will improve clinical outcomes in patients with HF. First, XOIs have unique positive inotropic effects, improving myocardial contraction and performance while simultaneously improving myocardial energy metabolism. Second, XOIs ameliorate endothelial dysfunction in humans with HF. Finally, XO activity is upregulated in the heart and vasculature of subjects with HF, which may in turn contribute to oxidative stress and/or increased uric acid levels. Together these findings form the rationale for the Controlled Efficacy and Safety Study of Oxypurinol Added to Standard Therapy in Patients with New York Heart Association (NYHA) class III - IV Congestive Heart Failure (OPT-CHF) trial (Food and Drug Adminstration IND 65,125), a Phase II - III prospective, randomised, double-blind, placebo-controlled trial, which will include patients with stable symptomatic HF in NYHA class III - IV congestive HF who are deemed clinically stable on a standard and appropriately maximised heart failure therapy regimen. The efficacy end point for OPT-CHF is a composite that incorporates measures of patient outcome and well-being.

Original languageEnglish
Pages (from-to)1509-1516
Number of pages8
JournalExpert Opinion on Investigational Drugs
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Fingerprint

Oxypurinol
Heart Failure
Safety
Therapeutics
Myocardial Contraction
Allopurinol
Xanthine Oxidase
Uric Acid
Energy Metabolism
Oxidative Stress
Placebos
Outcome Assessment (Health Care)
Food

Keywords

  • Clinical trial
  • Drug therapy
  • Heart failure
  • Oxidative stress
  • Xanthine oxidase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Rationale, design and organisation of an efficacy and safety study of oxypurinol added to standard therapy in patients with NYHA class III - IV congestive heart failure. / Freudenberg, Ronald S.; Schwarz, Richard P.; Brown, Joanne; Moore, Alan; Mann, Douglas; Givertz, Michael M.; Colucci, Wilson S.; Hare, Joshua.

In: Expert Opinion on Investigational Drugs, Vol. 13, No. 11, 01.11.2004, p. 1509-1516.

Research output: Contribution to journalArticle

Freudenberg, Ronald S. ; Schwarz, Richard P. ; Brown, Joanne ; Moore, Alan ; Mann, Douglas ; Givertz, Michael M. ; Colucci, Wilson S. ; Hare, Joshua. / Rationale, design and organisation of an efficacy and safety study of oxypurinol added to standard therapy in patients with NYHA class III - IV congestive heart failure. In: Expert Opinion on Investigational Drugs. 2004 ; Vol. 13, No. 11. pp. 1509-1516.
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