A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic and alpha2-adrenergic receptors on morbidity and mortality in patients with heart failure

Eur J Heart Fail. 2008 Jan;10(1):89-95. doi: 10.1016/j.ejheart.2007.10.012. Epub 2007 Dec 27.

Abstract

Background: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF).

Methods: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled.

Results: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class.

Conclusion: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Double-Blind Method
  • Esters / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / mortality
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Prospective Studies
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Tetrahydronaphthalenes / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / mortality

Substances

  • ADRA2A protein, human
  • Esters
  • Receptors, Adrenergic, alpha-2
  • Receptors, Dopamine D2
  • Tetrahydronaphthalenes
  • nolomirole