THE EFFECT OF EPLERENONE VERSUS PLACEBO ON CARDIOVASCULAR MORTALITY AND HEART FAILURE HOSPITALIZATION IN SUBJECTS WITH NYHA CLASS II CHRONIC SYSTOLIC HEART FAILURE

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2005-003351-12-IT
• Date of registration: 19/01/2007
• Prospective Registration: No
• Primary sponsor: PFIZER
• Public title: THE EFFECT OF EPLERENONE VERSUS PLACEBO ON CARDIOVASCULAR MORTALITY AND HEART FAILURE HOSPITALIZATION IN SUBJECTS WITH NYHA CLASS II CHRONIC SYSTOLIC HEART FAILURE
• Scientific title: THE EFFECT OF EPLERENONE VERSUS PLACEBO ON CARDIOVASCULAR MORTALITY AND HEART FAILURE HOSPITALIZATION IN SUBJECTS WITH NYHA CLASS II CHRONIC SYSTOLIC HEART FAILURE
• Date of first enrolment: 05/04/2006
• Target sample size: 3102
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003351-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Czech Republic, Greece, Hungary, Ireland, Italy, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent obtained prior to the initiation of any study procedures; 2. Male or female subjects, >/=55 years of age at the time informed consent is obtained; 3. Chronic systolic heart failure (HF) of either ischemic or non-ischemic etiology. a. Duration: at least 4 weeks; b. Left ventricular ejection fraction (LVEF): /=130 msec. It is mandatory that subjects with LVEF 31-35% must also have QRS duration >/=130 msec to be eligible for this trial. c. Functional Capacity: Currently NYHA II (in the investigator s opinion); d. Treatments (for ACE inhibitors, ARBs and b-blockers, optimal target or maximal tolerated dose [See Appendix 1 Optimal Target Doses of Angiotensin Converting Enzyme (ACE) Inhibitors, Angiotensin Receptor Blockers (ARBs) and b-Blockers] unless contraindicated). - Angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs); - b-blocker; - Diuretic, if clinically indicated to reduce fluid retention; 4. Serum potassium (K+) level 7=30 ml/min/1.73m2 within 24 hours prior to randomization (See Appendix 2 Calculation of Estimated Glomerular Filtration Rate (eGFR)). 6. Randomization must occur no later than 6 months from the date of admission to hospital for a cardiovascular reason (see definition of cardiovascular hospitalization below). If the subject is clinically stable, he or she may be randomized during admission for a cardiovascular reason. OR In the absence of a recent admission to hospital for a cardiovascular reason, documentation of a plasma concentration of B-type natriuretic peptide (BNP) of at least 250 pg/ml or amino-terminal proB-type natriuretic peptide (NT-proBNP) of at least 500 pg/ml for males and 750 pg/ml for females, within 15 days of randomization. 7. If the subject is a female, the following should apply. a. Have a negative serum pregnancy within 72 hours prior to the first dose of study drug, except if she previously had a total hysterectomy or is >65 years old; b. Agree to use an adequate form of contraception (Abstinence will not be considered an acceptable form of contraception) if she is of child-bearing potential. 8. Subjects previously treated with an aldosterone antagonist for >7 consecutive days will be allowed if they fulfill the following criteria: a. No history of clinically significant hyperkalemia or renal impairment during earlier use of an aldosterone antagonist; b. The aldosterone antagonist must have been discontinued for at least 3 months prior to randomization. A washout period of 48 hours is deemed adequate for subjects treated with an aldosterone antagonist for less than or equal to7 days. Subjects who have a bona fide need for an aldosterone antagonist must not be discontinued from treatment just to make them eligible for entry into this trial. 9. Subjects in whom the primary cause of heart failure is inoperable valve disease.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 year
Exclusion criteria:
1.Patients with severe chronic systolic heart failure, defined as patients who demonstrate symptoms usually at rest despite optimal medical therapy. 2.Patients with a myocardial infarction complicated by left ventricular systolic dysfunction and clinical heart failure within 30 days prior to randomization. 3.Patients with stroke within 30 days prior to randomization. 4.Patients who have had cardiac surgery within 30 days prior to randomization. 5.Patients who have had percutaneous coronary intervention (PCI) within 30 days prior to randomization. 6.Patients previously exposed to treatment with an aldosterone antagonist for >7 consecutive days, in whom the aldosterone antagonist has not been discontinued permanently for at least 3 months prior to randomization, or patients who have a history of clinically significant hyperkalemia or renal impairment during a previous exposure to an aldosterone antagonist. 7.Patients who require treatment with eplerenone, spironolactone or potassium canrenoate and either have prior NYHA class IV heart failure associated with a LVEF 180 mmHg and/or a diastolic blood pressure >110 mmHg. 9.Patients with symptomatic hypotension or having a systolic blood pressure <85 mmHg. 10.Patients, who in the opinion of the investigator, require treatment with potassium-sparing diuretics. 11.History of hypersensitivity to eplerenone or spironolactone. 12.Evidence of cardiogenic shock. 13.Patients in whom the primary cause of heart failure is surgically amenable valve disease, pericardial disease or an obstructive or restrictive cardiomyopathy. 14.Intra-aortic balloon pump or other mechanical assist device. 15.Patients awaiting cardiac transplantation. 16.Serum potassium >5.0 mmol/L within 24 hours prior to randomization. 17.Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 within 24 hours prior to randomization (See Appendix 2 Calculation of Estimated Glomerular Filtration Rate (eGFR)). 18.Concomitant use of potent cytochrome p450 3A4 (CYP3A4) inhibitors, such as but not limited to: a.Ketoconazole; b.Itraconazole; c.Nefazodone; d.Troleandomycin; e.Clarithromycin; f.Ritonavir; g.Nelfinavir. 19.Concomitant use of cytochrome p450 3A4 (CYP3A4) inducers, such as but not limited to: a.St.John s Wort; b.Rifampin; c.Carbamazepine; d.Phenytoin; e.Phenobarbitol. 20.Hemoglobin <10g/dL. 21.Patients with preexisting significant hepatic disease (for example, known positive serology for viral hepatitis) or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 times the upper limits of normal. 22.Patients status-post gastric bypass surgery, partial gastrectomy or other surgery of the gastrointestinal tract that may interfere with the absorption of eplerenone. 23.Patients with preexisting serious conditions (eg, cancer, Acquired Immunodeficiency Syndrome (AIDS).Patients with a previous history of cancer will be eligible if in the opinion of the investigator life expectancy is anticipated to be greater than 5 years. 24.Patients unable to give written informed consent. 25.Patients with a progressively fatal disease (except congestive heart failure) and/or life expectancy less than 3 years. 26.Patients receiving immunosuppressive or antineoplastic therapy. 27.Patients wi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic systolic heart failure
MedDRA version: 14.1 Level: PT Classification code 10007558 Term: Cardiac failure chronic System Organ Class: 10007541 - Cardiac disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Inspra
Product Code: NA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eplerenone
Concentration unit: mg milligram(s)
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: none

Main Objective: The primary objective of this trial is to evaluate the efficacy and safety of eplerenone plus standard heart failure (HF) therapy versus placebo plus standard HF therapy on the cumulative incidence of cardiovascular (CV) mortality or HF hospitalization (a composite primary endpoint).

Primary end point(s): Primary The primary efficacy endpoint is the first occurrence of cardiovascular (CV) mortality or heart failure (HF) hospitalization (following randomization);

Secondary ID(s)

2005-003351-12-CZ

A6141079