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
- Conditions
- Chronic systolic heart failureMedDRA version: 8.0 Level: LLT Classification code 10008908
- Registration Number
- EUCTR2005-003351-12-GB
- Lead Sponsor
- Pfizer Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 3102
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, =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): =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 randomization must be used.
OR
Left ventricular ejection fraction (LVEF) =35% in addition to QRS duration =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 ß-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 randomization.
5. Estimated glomerular filtration rate (eGFR) =30 ml/min/1.73m2 within 24 hours
prior to randomization.
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 fewer than 7
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 <0.35 (as in the RALES trial) [2] or heart failure or diabetes and a LVEF <0.40 after acute MI (as in EPHESUS trial).
8. Patients with uncontrolled hypertension, defined as having a systolic blood pressure >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.
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 uppe
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method