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

Phase 3

Terminated

• Conditions: Heart Failure, Congestive
• Interventions: Drug: Placebo to match enoximone; Drug: Enoximone; Drug: Metoprolol succinate; Drug: Placebo to match metoprolol succinate

• Registration Number: NCT00077948
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Over the last decade, it has become evident that certain beta-blocking agents (beta-blockers) exert a favorable effect on the natural history of mild to moderate chronic heart failure (CHF), including reducing mortality and hospitalization rate. However, as heart failure becomes more severe, beta-blockers become difficult to administer because of myocardial depression leading to hemodynamic intolerance. A recent clinical study demonstrated that subjects who could not tolerate the beta-blocker metoprolol experienced improved tolerability when low-dose, oral enoximone was administered prior to the introduction of metoprolol and during ongoing treatment. This study will investigate the hypotheses that by stabilizing subjects on enoximone first, advanced CHF subjects who are intolerant of beta-blockade will be able to 1) tolerate the effects of beta-blocker therapy, and 2) have clinical benefit that is due to the combination of both enoximone and extended-release metoprolol succinate (ER metoprolol). Support for these hypotheses will be sought by demonstrating that, as compared to placebo, low-dose, oral enoximone plus ER metoprolol will increase left ventricular ejection fraction (LVEF), improve symptoms of heart failure, and improve submaximal exercise tolerance in subjects with CHF.

Study Timeline

• Study Start: 2003-07
• Study First Submitted: 2004-02-13
• Study First Submitted QC: 2004-02-17
• Study First Posted: 2004-02-18
• Primary Completion: 2005-06
• Study Completion: 2005-06
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-08
• Last Update Posted: 2014-01-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo enoximone plus placebo ER metoprolol	Placebo to match enoximone	-
placebo enoximone plus active ER metoprolol	Placebo to match enoximone	-
active enoximone plus active ER metoprolol	Metoprolol succinate	-
placebo enoximone plus active ER metoprolol	Metoprolol succinate	-
placebo enoximone plus placebo ER metoprolol	Placebo to match metoprolol succinate	-
active enoximone plus active ER metoprolol	Enoximone	-

Primary Outcome Measures

Name	Time	Method
Proportion of participants experiencing improved metoprolol tolerability when coadministered with enoximone	Baseline to Week 36	Improved tolerability measured by increased left ventricular ejection fraction (LVEF), improvement of heart failure symptoms, and improvement in submaximal exercise tolerance.

Trial Locations

Locations (2)

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of Colorado; 🇺🇸 Denver, Colorado, United States