Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack

April 7, 2006 updated by: NHS Greater Glasgow and Clyde

The Effects of Eplerenone on Left Ventricular Remodelling Post-Acute Myocardial Infarction: a Double-Blind Placebo-Controlled Cardiac MR-Based Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Scotland
      • Glasgow, Scotland, United Kingdom, G11 6NT
        • Western Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2005

Study Registration Dates

First Submitted

August 18, 2005

First Submitted That Met QC Criteria

August 18, 2005

First Posted (Estimate)

August 19, 2005

Study Record Updates

Last Update Posted (Estimate)

April 10, 2006

Last Update Submitted That Met QC Criteria

April 7, 2006

Last Verified

November 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WN04CA024
  • Eudract number 2004-004399-35

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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