Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack

Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00132093
• Other study ID #: WN04CA024
• Secondary ID: Eudract number 2
• Status: Completed
• Phase: Phase 4
• First received: August 18, 2005
• Last updated: April 7, 2006
• Start date: April 2005

Study information

• Verified date: November 2004
• Source: NHS Greater Glasgow and Clyde
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Ventricular Remodeling

Intervention

Drug:
• Eplerenone

Locations

Country	Name	City	State
United Kingdom	Western Infirmary	Glasgow	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
NHS Greater Glasgow and Clyde

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. Epub 2003 Mar 31. Erratum in: N Engl J Med. 2003 May 29;348(22):2271. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Comparison of lab blood markers of LV remodelling over 6 months, comparing treatment group to placebo group
Secondary	Comparison of neurohormonal levels over 6 months, comparing treatment group to placebo group
Secondary	Comparison of cardiac electrical stability (heart rate variability, QT dispersion) over 6 months, comparing treatment group to placebo group
Secondary	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