ESSENTIAL-The Studies of Oral Enoximone Therapy in Advanced Heart Failure

Study Overview
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Brief Summary
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To determine if low-dose enoximone therapy is an effective treatment for advanced chronic heart failure.

Detailed Description
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The study is a randomized, double-blind, multicenter, parallel group, placebo-controlled trial of oral enoximone in approximately 700 subjects with advanced chronic heart failure of either ischemic or nonischemic etiology receiving optimal conventional heart failure therapy. Eligible subjects will be randomized in a 1:1 ratio to receive either enoximone or placebo at the Randomization Visit. The initial dose of study drug will be 25 mg t.i.d.(3xday) and will be administered immediately after randomization. Subjects who tolerate this initial dose will be continued on 25 mg t.i.d. for at least two weeks. After two weeks, eligible subjects will be titrated to 50 mg t.i.d. for the duration of the study.

Official Title
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ESSENTIAL Protocol No. My-021 and Protocol No. My-026, Each Titled: A Phase III, Randomized, Double-Blind, Multicenter, Parallel Group, Placebo-Controlled Study of Oral Enoximone vs. Placebo in Advanced Chronic Heart Failure Subjects

Conditions
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Heart Failure, Congestive

Intervention / Treatment
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* Drug: Enoximone
* Drug: Enoximone placebo


Participation Criteria
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Eligibility Criteria
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In order to be considered eligible subjects, the following entry criteria must be met: At least 18 years of age ischemic or nonischemic cardiomyopathy NYHA Class III or IV one hospitalization, or two outpatient visits, for the treatment of worsening heart failure within 12 months requiring the administration of I.V. heart failure therapy LVEDD >3.2 cm/m2 or >=6.0 cm LVEF of less than or equal to 30% concomitant treatment with optimal conventional heart failure therapy Exclusion Criteria Subjects who meet any one of the following criteria will be deemed ineligible for participation in the study: Subjects on the following concomitant medications: Calcium antagonists other than amlodipine or felodipine Flecainide, encainide, propafenone, dofetilide or disopyramide Subjects receiving I.V. positive inotropic agents within seven days of the Screening Visit or Randomization Visit Subjects receiving a human B-type natriuretic peptide, including nesiritide, within seven days of the Screening Visit or Randomization Visit Subjects receiving oral or I.V. phosphodiesterase III inhibitors (PDEI III), including levosimendan and cilostazol, within seven days of the Screening Visit or Randomization Visit Subjects with active hepatic (screening serum total bilirubin >= 3.0 mg/dl (>=51.3 umol/l), renal (screening serum creatinine >= 2.0 mg/dl (=178.8 umol/l)), hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease Subjects with a serum potassium <4.0 mEq/L or >5.5 mEq/L (<4.0 mmol/l or >5.5 mmol/l) at Randomization Visit Subjects with a magnesium level of <1.0 mEq/L (<0.5 mmol/l) at Randomization Visit (Visit 0) Subjects with a serum digoxin of >1.2 ng/ml (>1.5 nmol/l) or a serum digitoxin of >20 ng/ml (>26.2 nmol/l) at the Randomization Visit are excluded. A target serum digoxin level of <=1.0 ng/ml (<=1.3 nmol/l) is recommended

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enoximone<br> | Drug: Enoximone<br>* Participants receive oral enoximone<br>|
| Placebo Comparator: Placebo<br> | Drug: Enoximone placebo<br>* Participants receive placebo to match enoximone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomization to all-cause mortality or cardiovascular hospitalization |  | Baseline to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient Global Assessment score | Improvement in quality of life assessed by the Patient Global Assessment patient-reported outcomes tool | Baseline to Month 6 | 
| Change in Six-Minute Walk Test | Improvement in quality of life assessed by the Six-Minute Walk Test, a measure of submaximal exercise tolerance | Baseline to Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHF, heart, failure, congestive, enoximone, phosphodiesterase, inhibitor