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

• ClinicalTrials.gov Identifier: NCT00051285
• Recruitment Status: Terminated
• First Posted: January 9, 2003
• Last Update Posted: January 10, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Heart Failure, Congestive	Drug: Enoximone; Drug: Enoximone placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 1800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: February 2002
• Actual Primary Completion Date: June 2005
• Actual Study Completion Date: June 2005

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Time from randomization to all-cause mortality or cardiovascular hospitalization [ Time Frame: Baseline to Month 6 ]

Secondary Outcome Measures :

1. Change in Patient Global Assessment score [ Time Frame: Baseline to Month 6 ]
   Improvement in quality of life assessed by the Patient Global Assessment patient-reported outcomes tool
2. Change in Six-Minute Walk Test [ Time Frame: Baseline to Month 6 ]
   Improvement in quality of life assessed by the Six-Minute Walk Test, a measure of submaximal exercise tolerance

Eligibility Criteria

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

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00051285
• Other Study ID Numbers: ESSENTIAL: My-021 and My-026
• First Posted: January 9, 2003
• Last Update Posted: January 10, 2014
• Last Verified: January 2014

Keywords provided by Gilead Sciences:

CHF; heart; failure; congestive; enoximone; phosphodiesterase; inhibitor

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases; Enoximone; Cardiotonic Agents; Vasodilator Agents; Phosphodiesterase 3 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs