To assess the impact of eplerenone on cardiovascularmortality and morbidity in patients with acutemyocardial infarction (STEMI) when initiated withinthe first 24 hours of onset of symptoms (preferablyduring the first 12 hours)To investigate the…
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint:
Time to first event of :
- Cardiovascular mortality
- Re-hospitalization or extended initial hospital stay due to diagnosis of
heart failure
- Sustained ventricular tachycardia or fibrillation
- Ejection fraction <= 40% after 1 month or BNP >200 pg/ml or NT-proBNP >450
pg/ml (age<50 years); >900 pg/ml (age 50-75 years) or >1800 pg/ml (age>75
years) after 1 month.
Secondary outcome
1. Time to cardiovascular mortality.
2. Time to diagnosis of heart failure.
3. Time to first and each subsequent episode (after an event free interval of >=
48 hours) of
sustained ventricular tachycardia or ventricular fibrillation.
4. Time to first recorded ejection fraction of <= 40% (recorded 1 month or later
postrandomization).
5. Time to BNP >200 pg/ml or NT-proBNP >450, >900 or >1800 pg/ml for ages <50
years,
50-75 years and >75 years, respectively (recorded 1 month or later
post-randomization).
6. Time to decision to provide an implantable cardioverter defibrillator (ICD)
or cardiac
resynchronization therapy (CRT).
7. Time to second or subsequent non-fatal myocardial infarction.
8. QRS duration at 6 months post-randomization.
9. Left atrial diameter (recorded on each occasion an echocardiogram is
conducted).
10. Change in serum levels of biomarkers at 6 months post-randomization. Blood
samples
for biomarkers will be stored and analyzed post completion of the study.
Background summary
Eplerenone, an antagonist at the mineralocorticoid receptor, has wide-ranging
effects on the
heart at a cellular and tissue level. The EPHESUS trial demonstrated a
significant
improvement in survival when eplerenone is initiated three to fourteen days
following acute
myocardial infarction complicated by left ventricular systolic dysfunction and
signs and
symptoms of congestive heart failure. Although evidence exists that cardiac
remodeling
begins almost immediately after a heart attack, the average delay between
myocardial
infarction and the initiation of eplerenone was seven days, which may miss an
early window
of opportunity to influence the myocardium favourably.
In addition, based on the current practice patterns, many patients have already
been
discharged from hospital by the time eplerenone would be started.
This study will test the hypothesis that starting eplerenone promptly after
infarction will be
safe and efficacious in reducing adverse outcomes with potential long term
benefits.
Study objective
To assess the impact of eplerenone on cardiovascular
mortality and morbidity in patients with acute
myocardial infarction (STEMI) when initiated within
the first 24 hours of onset of symptoms (preferably
during the first 12 hours)
To investigate the effect of eplerenone on serum
biomarkers of collagen metabolism / myocardial
fibrosis (eg, ICTP, PINP, PIIINP) and cardiovascular
risk (eg, ADMA and adiponectin) and to potentially
relate these measures to clinical outcomes.
Study design
A multicentre, randomized, double-blind, placebocontrolled,
2-arm, parallel group trial comparing
eplerenone plus standard of care to placebo plus
standard of care in patients post-myocardial infarction.
Intervention
Treatment will be administered daily for a minimum
period of 6 months and a maximum period of
approximately 17 months. Predetermined study visits
will take place at day 1, week 1, week 4, 6 months and 6
monthly thereafter until the study is completed.
Study burden and risks
ADVERSE EVENTS:
Most commonly seen: High potassium in the blood, dizziness, low blood
pressure, diarrhea, nausea and kidney problems (such as increased urination).
Less commonly seen (less than 1 in 100 patients): Dehydration, high
cholesterol. high triglycerides, low sodium in the blood, insomnia, headache,
abnormal heart beat, dizziness when sitting or standing up too quickly, blood
clot in the leg, irritation of the throat, flatulence, vomiting, skin itching,
increased sweating, back pain, leg cramps, malaise, increase in BUN, increase
in creatinine level in the blood, infection of the kidney and increase in white
blood cells in the blood.
East 42nd Street
New York 10017, New York
US
East 42nd Street
New York 10017, New York
US
Listed location countries
Age
Inclusion criteria
1. Evidence of a personally signed and dated informed consent document obtained prior to the initiation of any study procedures and indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Subjects must be male or non-pregnant female aged >=18 years of age at the time informed consent is obtained.
4. If the subject is female, she must be post-menopausal,or is surgically sterile, and is not lactating.
5. Subjects must have experienced a myocardial infarction (STEMI) within the previous 24 hours confirmed by symptoms and ECG.
Exclusion criteria
1. The subject has received any investigational medication or used any investigational device within 30 days prior to the first dose of study medication or is actively participating in any investigational drug or device study, or is scheduled to receive an investigational drug other than eplerenone or to use an investigational device during the course of the study.
2. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Subjects who have experienced a previous myocardial infarction may be included provided all other inclusion / exclusion criteria are met.
3. Subjects with inability to follow protocol procedures according to the investigation.
4. The subject has any condition which, in the opinion of the Investigator, makes participation in this study not in the best interest of the subject.
5. The subject has a severe organic disorder or has had surgery or disease of the gastrointestinal tract which, in the opinion of the Investigator, may interfere with the absorption, pharmacokinetics, or elimination of the study drug.
6. The subject has a co-morbid condition that would be expected to result in death during the next year (eg, terminal cancer, AIDS, etc) including subjects receiving immunosuppressive or antineoplastic therapy.
7. The subject has current evidence of alcohol or drug abuse problems, which in the Investigator's opinion, precludes study participation.
8. Subjects treated with eplerenone or other aldosterone antagonists within the past 1 month.
9. The subject has an implanted cardiac defibrillator (ICD).
10. The subject is awaiting cardiac transplant.
11. The subject has uncontrolled hypotension (SBP<90mmHg).
12. Subjects with eGFR <=30ml/min (based on admission serum creatinine and the MDRD formula) or serum creatinine >=220µmol/L.
13. Subjects with a known low ejection fraction of less than 40% or any previous history of heart failure.
14. Patients who have haemodynamically relevant aortic or mitral valve stenosis as judged by the investigator.
15. Subjects with a diagnosis of hypertrophic cardiomyopathy.
16. Subjects who have had cardiac surgery within 30 days prior to randomization.
17. Concomitant use of potassium sparing diuretics (eg, spironolactone, triamterene or amiloride) or subjects who in the opinion of the investigator require treatment with potassium sparing diuretics. Use of potassium preparations or supplements will be allowed on a case by case basis at the discretion of the Investigator.
18. Concomitant use of potent cytochrome p450 3A4 (CYP3A4) inhibitors, such as but not limited to: ketoconazole; itraconazole; nefazodone; troleandomycin; clarithromycin; ritonavir; nelfinavir.
19. Concomitant use of cytochrome p450 3A4 (CYP3A4) inducers, such as but not limited to: St. John*s wort; rifampin; carbamazepine; phenytoin; phenobarbitol.
20. Subjects who are likely to require treatment during the trial period with drugs not permitted by this protocol.
21. Subjects 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. Subjects with a known sensitivity or intolerance to eplerenone, spironolactone or tablet excipients.
23. Donation of blood or blood products for transfusion at any time during the trial or until 30 days after completion of treatment.
24. Prisoners or subjects who are compulsorily detained (involuntary incarcerated) for treatment of either a psychiatric or physical illness must not be enrolled into this study.
25. The subject has been previously admitted to the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-019844-38-NL |
| ClinicalTrials.gov | NCT01176968 |
| CCMO | NL33120.100.10 |