Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack

This study has been completed.
Sponsor:
Information provided by:
NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier:
NCT00132093
First received: August 18, 2005
Last updated: April 7, 2006
Last verified: November 2004
  Purpose

The purpose of this study is to ascertain whether treatment with the drug eplerenone, taken early after a heart attack, prevents or reduces some of the adverse changes that may otherwise naturally occur within the heart muscle, that lead ultimately to weakening of the heart muscle and premature death.


Condition Intervention Phase
Myocardial Infarction
Drug: Eplerenone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effects of Eplerenone on Left Ventricular Remodelling Post-Acute Myocardial Infarction: a Double-Blind Placebo-Controlled Cardiac MR-Based Study

Resource links provided by NLM:


Further study details as provided by NHS Greater Glasgow and Clyde:

Primary Outcome Measures:
  • Change in left ventricular (LV) end-systolic volume over 6 months, based on cardiac magnetic resonance imaging (MRI) measurements, comparing treatment group to placebo group

Secondary Outcome Measures:
  • Comparison of lab blood markers of LV remodelling over 6 months, comparing treatment group to placebo group
  • Comparison of neurohormonal levels over 6 months, comparing treatment group to placebo group
  • Comparison of cardiac electrical stability (heart rate variability, QT dispersion) over 6 months, comparing treatment group to placebo group
  • Analysis of DNA at baseline between and within the eplerenone group and the control group – to see if mutations in the gene that encodes aldosterone synthase - CYP112B - predict remodelling and response to aldosterone blockade

Estimated Enrollment: 100
Study Start Date: April 2005
Detailed Description:

Despite advances in detection and treatment of coronary artery disease, and numerous campaigns to promote healthier lifestyles, ischaemic heart disease (IHD) remains very common worldwide but particularly in the West of Scotland. Following a heart attack, the main pumping chamber - the left ventricle (LV) - will be significantly damaged in around 40% of patients to the extent that it fails to pump as effectively as before. Despite current medical treatment, this failing LV slowly but continuously deteriorates with time (this is known as LV remodelling), which can lead to "heart failure".

Eplerenone, a hormone blocker (aldosterone antagonist), has been shown to reduce death rates and improve symptoms in patients with acute heart attacks - or myocardial infarctions (MI)- who additionally have impaired LV function and heart failure (or diabetes). The researchers assume that eplerenone may exert some of these beneficial effects by preventing or reducing this LV remodelling process.

Cardiac MRI provides very accurate assessment of LV function, such that small numbers of patients only are required to detect differences in LV function over time when comparing one group against another. The researchers are therefore comparing sequential cardiac MRI appearances and measurements in patients with acute MI and LV impairment at baseline (within 2 weeks of the acute MI), 3 months and 6 months. After the first MRI scan, patients are assigned to eplerenone or placebo in addition to usual secondary preventive therapy (double-blinded), which continues for 6 months, after which each patient's involvement in the trial is finished.

As eplerenone has been shown to benefit those with acute MI plus LV impairment and heart failure (or diabetes), such patients cannot ethically be put into a trial in which they may potentially be placed in a placebo group. For this reason, a slightly different cohort of patients are being used - acute MI with LV impairment but without clinical heart failure or diabetes.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 or above
  2. Acute myocardial infarction within last 1-14 days (defined by typical electrocardiogram [ECG] changes and/or elevated cardiac enzymes to at least twice the upper limit of normal)
  3. Left ventricular systolic dysfunction (LVSD) based on echocardiographic wall motion score index (WMSI) and left ventricular ejection fraction (LVEF) < 40%
  4. Ability to give written informed consent

Exclusion Criteria:

  1. Clinical or radiological heart failure
  2. Established diabetes mellitus
  3. Current use of potassium (K)-sparing diuretics, clarithromycin, nefazodone, itraconazole, ketoconazole, ritonavir, nelfinavir, tacrolimus, cyclosporin.
  4. Serum creatinine > 220 µmol/l
  5. Serum potassium > 5.0 mmol/l
  6. Pregnancy
  7. Addison’s disease
  8. MRI-incompatible (ferrous) sulphate prosthesis
  9. Claustrophobia (unable to tolerate MR environment)
  10. Concurrent use of phenytoin, carbamazepine, rifampicin or St. John’s Wort (reduce efficacy of eplerenone).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00132093

Locations
United Kingdom
Western Infirmary
Glasgow, Scotland, United Kingdom, G11 6NT
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
Investigators
Principal Investigator: Robin AP Weir, MBChB, BSc, MRCP NHS Greater Glasgow and Clyde
Study Director: Henry J Dargie, MBChB,FRCP NHS Greater Glasgow and Clyde
Study Director: John JV McMurray, FRCP,MD,FESC University of Glasgow
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00132093     History of Changes
Other Study ID Numbers: WN04CA024, Eudract number 2004-004399-35
Study First Received: August 18, 2005
Last Updated: April 7, 2006
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by NHS Greater Glasgow and Clyde:
Left ventricular remodelling
Acute myocardial infarction
Left ventricular dysfunction
Eplerenone
Cardiac Magnetic Resonance Imaging

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ventricular Remodeling
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Pathological Conditions, Anatomical
Eplerenone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014