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

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

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

Study Overview

• Status: Terminated
• Conditions: Heart Failure, Congestive
• Intervention / Treatment: Drug: Enoximone; Drug: Enoximone placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment: 1800
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Enoximone placebo; Participants receive placebo to match enoximone
Experimental: Enoximone	Drug: Enoximone; Participants receive oral enoximone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: January 7, 2003
• First Submitted That Met QC Criteria: January 8, 2003
• First Posted (Estimate): January 9, 2003

Study Record Updates

• Last Update Posted (Estimate): January 10, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: CHF; heart; inhibitor; failure; enoximone; congestive; phosphodiesterase
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Enoximone
• Other Study ID Numbers: ESSENTIAL: My-021 and My-026