Enoximone Plus Extended-Release Metoprolol Succinate in Subjects With Advanced Chronic Heart Failure

NCT00077948 | Terminated Phase 3

• 1 other identifier: EMPOWER (Protocol My-023)
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 2

Brief Summary

Beta-blocker medications have been shown to improve heart function and prolong the lives of patients with chronic heart failure (CHF). Some people with advanced CHF have difficulty taking beta-blocker medications due to troublesome side effects, such as low blood pressure and/or low heart rate, severe tiredness, dizziness, or shortness of breath. In other words, they have difficulty tolerating beta-blocker medications. The purpose of this study is to determine if enoximone can improve a patient's ability to tolerate a beta-blocker medication.

Conditions

Heart Failure, Congestive

Keywords

positive inotrope; enoximone; beta-blocker; intolerant

Outcome Measures

Primary Outcomes (1)

• Proportion of participants experiencing improved metoprolol tolerability when coadministered with enoximone

  Improved tolerability measured by increased left ventricular ejection fraction (LVEF), improvement of heart failure symptoms, and improvement in submaximal exercise tolerance.

  Baseline to Week 36

Study Arms (3)

active enoximone plus active ER metoprolol

EXPERIMENTAL

Drug: Enoximone; Drug: Metoprolol succinate

placebo enoximone plus active ER metoprolol

ACTIVE COMPARATOR

Drug: Metoprolol succinate; Drug: Placebo to match enoximone

placebo enoximone plus placebo ER metoprolol

PLACEBO COMPARATOR

Drug: Placebo to match enoximone; Drug: Placebo to match metoprolol succinate

Interventions

Enoximone DRUG

Enoximone administered orally

active enoximone plus active ER metoprolol

Metoprolol succinate DRUG

Metoprolol succinate administered orally

active enoximone plus active ER metoprolol; placebo enoximone plus active ER metoprolol

Placebo to match enoximone DRUG

Placebo to match match enoximone administered orally

placebo enoximone plus active ER metoprolol; placebo enoximone plus placebo ER metoprolol

Placebo to match metoprolol succinate DRUG

Placebo to match metoprolol succinate administered orally

placebo enoximone plus placebo ER metoprolol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be considered an eligible subject, all of the following entry criteria must be met:
• Subjects must be competent to provide informed written consent. Subjects must sign an IRB/IEC approved informed consent form prior to the initiation of any study procedures.
• Subjects must be 18 years of age or older.
• Subjects must have ischemic or nonischemic cardiomyopathy with symptoms of NYHA Class III or IV chronic heart failure.
• Subjects must have a LVEF of less than or equal to 35%, measured within 60 days of the Screening Visit. LVEF must be assessed by radionuclide ventriculography (MUGA). If the subject has experienced any cardiovascular events, has undergone any interventions, or received any changes in treatment that may have affected LV function since the most recent EF measurement, an LVEF measurement must be completed prior to the subject being randomized.
• Subjects must have a left ventricular end diastolic dimension (LVEDD) of \>2.7 cm/m2 as measured by 2-D ECHO within 12 months of the Screening Visit.
• Subjects must be on optimal conventional heart failure therapy (with the exception of a beta-blocker), including an ACEI for at least 30 days prior to the Screening Visit, or the subject must have had a trial of an ACEI and proven to be intolerant, or the subject must be taking an ARB for at least 30 days prior to the Screening Visit or proved to be intolerant. Optimal conventional therapy may also include spironolactone, digitalis glycosides, diuretics, or other vasodilators.
• Subjects must have failed the initiation, or the up-titration, of a beta-blocker drug due to hemodynamic intolerance within 12 months prior to the Screening Visit. Failure to tolerate beta-blockade for hemodynamic reasons is defined as worsening signs and symptoms of chronic heart failure, hypotension accompanied with symptoms, or evidence of organ hypoperfusion, which in the judgment of the treating physician precluded further treatment with the beta-blocker. This beta-blocker intolerance must have been documented prior to Screening, and a narrative description of the intolerance must be approved by Myogen prior to Randomization.

You may not qualify if:

• Subjects who meet any one of the following criteria will be deemed ineligible for participation in the study:
• Subjects with CHF due to or associated with uncorrected primary valvular disease, uncorrected thyroid disease, obstructive/hypertrophic cardiomyopathy, pericardial disease, amyloidosis, active myocarditis, malfunctioning artificial heart valve, uncorrected congenital heart disease, isolated right-sided heart failure, or primary pulmonary hypertension.
• Subjects who have undergone a cardiac revascularization, valvular surgery, or bi-ventricular resynchronization procedure within 60 days prior to the Screening Visit.
• Subjects listed for heart transplantation who are expected to be transplanted within 6 months of randomization.
• Subjects who have had a myocardial infarction within 90 days prior to the Screening Visit.
• Subjects with an ECG recorded at the Screening Visit showing any of the following: 1) evidence of transmural ischemia (dynamic ST elevation or ST elevation associated with ischemic symptoms), or 2) ventricular tachycardia (VT) or premature ventricular complexes (PVCs) associated with symptoms, or 3) VT of greater than or equal to 6 beats
• Subjects with sustained (\>15 seconds) VT, unless precipitated by an event such as an acute myocardial infarction, induction by catheter placement, or by an electrophysiology procedure, or addressed by AICD placement.
• Subjects with an AICD that has fired for any ventricular arrhythmia within 90 days of the Randomization Visit.
• Subjects with a documented diagnosis of angina that meets either of the following criteria: 1) angina diagnosed as unstable at any time within the 60 days prior to the Screening Visit or 2) angina is the primary symptom that limits daily physical activity
• Subjects who have had ventricular reduction surgery or cardiac myoplasty.
• Subjects on a mechanical assist device.
• Subjects with evidence of a concomitant disease that may interfere with the natural course of the subject's underlying heart failure for the duration of the trial.
• Subjects having a concomitant life-threatening disease for which their life expectancy is estimated to be less than one year.
• Subjects with uncontrolled insulin-dependent diabetes mellitus with a history of frequent hypoglycemic episodes or frequent hospitalizations for hyperglycemia.
• Subjects on the following concomitant medications at the time of Screening are excluded from participating in the study: 1) Calcium antagonists other than amlodipine or felodipine; 2) Flecainide, encainide, propafenone, sotalol, dofetilide or disopyramide; 3) Subjects receiving i.v. positive inotropic agents within seven days of the Screening Visit or Randomization Visit; 4) Subjects receiving a human BNP, including nesiritide, within seven days of the Screening Visit or Randomization Visit; 5) Subjects receiving oral or i.v. type-III PDE inhibitors within seven days of the Screening Visit or Randomization Visit.

Sponsors & Collaborators

• Gilead Sciences: lead
• AstraZeneca: collaborator

Study Sites (2)

University of Colorado

Denver, Colorado, 80262, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Enoximone; Metoprolol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2004
• First Posted: February 18, 2004
• Study Start: July 1, 2003
• Primary Completion: June 1, 2005
• Study Completion: June 1, 2005
• Last Updated: January 10, 2014

Record last verified: 2014-01

Locations

US (2)