Rationale and design of the enoximone clinical trials program.
BACKGROUND
Chronic heart failure is a disease syndrome characterized in its advanced stages by a poor quality of life, frequent hospitalizations, and a high risk of mortality. In advanced and ultra-advanced chronic heart failure, many treatment options, such as cardiac transplantation and mechanical devices, are severely limited by availability and cost. Short-term Phase II clinical trials suggest that low-dose oral inotropic therapy with enoximone may improve hemodynamics and exercise capacity, without adversely affecting mortality, in selected subjects with advanced chronic heart failure. Based on these data, the ability of enoximone to deliver safe and efficacious palliative treatment of advanced/ultra-advanced chronic heart failure is being evaluated in Phase III clinical trials.


RESULTS
The Enoximone Clinical Trials Program is a series of 4 clinical trials designed to evaluate the safety and efficacy of oral enoximone in advanced chronic heart failure. ESSENTIAL I and II (The Studies of Oral Enoximone Therapy in Advanced Heart Failure) will investigate the effects of oral enoximone on all-cause mortality and cardiovascular hospitalization, submaximal exercise capacity, and quality of life in subjects with New York Heart Association Class III/IV chronic heart failure. EMOTE (Oral Enoximone in Intravenous Inotrope-Dependent Subjects) will evaluate the potential of oral enoximone to wean subjects with ultra-advanced chronic heart failure from chronic intravenous inotropic therapy to which they have been shown to be dependent. EMPOWER (Enoximone Plus Extended-Release Metoprolol Succinate in Subjects with Advanced Chronic Heart Failure) will explore the potential of enoximone to increase the tolerability of continuous release metoprolol in subjects shown previously to be hemodynamically intolerant to beta-blocker treatment.


CONCLUSIONS
These studies are Phase III, multicenter, randomized, double-blinded, placebo-controlled trials designed to test the general hypothesis that chronic oral administration of low doses of enoximone can produce beneficial effects in subjects with advanced or ultra-advanced chronic heart failure.
Lowes
Brian D
BD
University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Shakar
Simon F
SF
Metra
Marco
M
Feldman
Arthur M
AM
Eichhorn
Eric
E
Freytag
J William
JW
Gerber
Michael J
MJ
Liard
Jean-Francois
JF
Hartman
Craig
C
Gorczynski
Rick
R
Evans
Gwyn
G
Linseman
Jennifer V
JV
Stewart
Jennifer
J
Robertson
Alastair D
AD
Roecker
Ellen B
EB
Demets
David L
DL
Bristow
Michael R
MR
D000284:Administration, Oral; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017335:Enoximone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D015337:Multicenter Studies as Topic; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D017335:Enoximone