THE EFFECT OF EPLERENONE VERSUS PLACEBO ON CARDIOVASCULAR MORTALITY AND HEART FAILURE HOSPITALISATION IN SUBJECTS WITH NYHA CLASS II CHRONIC SYSTOLIC HEART FAILURE (EMPHASIS-HF) - EMPHASIS-HF

• Register: EUCTR
• Last refreshed on: 29 May 2012
• Main ID: EUCTR2005-003351-12-GR
• Date of registration: 28/07/2006
• Prospective Registration: Yes
• Primary sponsor: Pfizer Hellas AE
• Public title: THE EFFECT OF EPLERENONE VERSUS PLACEBO ON CARDIOVASCULAR MORTALITY AND HEART FAILURE HOSPITALISATION IN SUBJECTS WITH NYHA CLASS II CHRONIC SYSTOLIC HEART FAILURE (EMPHASIS-HF) - EMPHASIS-HF
• Scientific title: THE EFFECT OF EPLERENONE VERSUS PLACEBO ON CARDIOVASCULAR MORTALITY AND HEART FAILURE HOSPITALISATION IN SUBJECTS WITH NYHA CLASS II CHRONIC SYSTOLIC HEART FAILURE (EMPHASIS-HF) - EMPHASIS-HF
• Date of first enrolment: 30/01/2007
• Target sample size: 2584
• 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 Other specify the comparator: Standard Therapy

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
1. Written informed consent obtained prior to the initiation of any study procedures
2. Male or female subjects, = 60 years of age at the time informed consent is obtained
3. Chronic systolic heart failure (HF) of either ischaemic or non-ischaemic aetiology:

a. Duration: at least 4 weeks

b. Left ventricular ejection fraction (LVEF): = 30% by echocardiography, contrast ventriculography, magnetic resonance imaging or nuclear imaging, based on local clinical practice. The most recent measurement within 6 months prior to randomisation must be used.

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 unless contraindicated):

· Angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs)

· ß-blocker

· Diuretic, if clinically indicated to reduce fluid retention

4. Serum potassium (K+) level = 5.0mmol/L within 24 hours prior to randomisation

5. Estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2 within 24 hours prior to randomisation.

6. Randomisation must occur no later than 90 days from the date of admission for index cardiovascular (CV) hospitalisation. (If clinically stable, the subject may be randomised during this index cardiovascular (CV) hospitalisation.)

7. If the subject is a female of childbearing potential, she must:

a. Have a negative serum pregnancy within 72 hours prior to the first dose of study drug
AND
b. Agree to use an adequate form of contraception (Abstinence will not be considered an acceptable form of contraception.)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects presenting with any of the following will not be included in the trial:

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 randomisation

3. Patients with stroke within 30 days prior to randomisation

4. Patients who have had cardiac surgery within 30 days prior to randomisation

5. Patients who have had percutaneous coronary intervention (PCI) within 30 days prior to randomisation

6. Patients, who in the opinion of the investigator, require treatment with eplerenone, spironolactone or potassium canrenoate

7. Patients with uncontrolled hypertension, defined as having a systolic blood pressure = 180 mmHg and/or a diastolic blood pressure = 110 mmHg

8. Patients with symptomatic hypotension or having a systolic blood pressure = 85 mmHg

9. Patients, who in the opinion of the investigator, require treatment with potassium-sparing diuretics or potassium supplements

10. History of hypersensitivity to eplerenone or spironolactone

11. Evidence of cardiogenic shock

12. Patients in whom the primary cause of heart failure is valve disease, pericardial disease or an obstructive or restrictive cardiomyopathy .

13. Intra-aortic balloon pump or other mechanical assist device

14. Patients awaiting cardiac transplantation

15. Serum potassium > 5.0 mmol/L within 24 hours prior to randomisation

16. Estimated glomerular filtration rate (eGFR) =30 ml/min/1.73m2 within 24 hours prior to randomisation.

17. 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


18. 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

19. Hemoglobin <10g/dL

20. 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

21. Patients status-post gastric bypass surgery, partial gastrectomy or other surgery of the gastrointestinal tract that may interfere with the absorption of eplerenone


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

Health Condition(s) or Problem(s) studied

Chronic systolic heart failure
MedDRA version: 8.0 Level: LLT Classification code 10008908

Intervention(s)

Product Name: Inspra
Product Code: N/A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eplerenone
CAS Number: 107724-20-9
Other descriptive name: Methyl hydrogen (7a,11a,17a)-9,11-epoxy-17-hydroxy-3-oxopregn-4-ene-7,21-dicarboxylate?-lactone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25 -
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective:

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 and HF hospitalisation (a composite primary endpoint).

Primary end point(s): The primary efficacy endpoint is the first occurrence of cardiovascular (CV) mortality and heart failure (HF) hospitalisation.

Cardiovascular (CV) mortality is defined as death due to:
Heart Failure
Myocardial infarction
Cardiac arrhythmia
Stroke/cerebral vascular accident (CVA) or transient ischaemic attack (TIA)
Other CV cause (e.g., aneurysm or pulmonary embolism)

Hospitalisation for HF

Secondary ID(s)

N/A

2005-003351-12-CZ

A6141079