Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack

NCT00132093 | Completed Phase 4

• 2 other identifiers: WN04CA024Eudract number 2004-004399-35
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myocardial Infarction

Keywords

Left ventricular remodelling; Acute myocardial infarction; Left ventricular dysfunction; Eplerenone; Cardiac Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Interventions

Eplerenone DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or above
• 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)
• Left ventricular systolic dysfunction (LVSD) based on echocardiographic wall motion score index (WMSI) and left ventricular ejection fraction (LVEF) \< 40%
• Ability to give written informed consent

You may not qualify if:

• Clinical or radiological heart failure
• Established diabetes mellitus
• Current use of potassium (K)-sparing diuretics, clarithromycin, nefazodone, itraconazole, ketoconazole, ritonavir, nelfinavir, tacrolimus, cyclosporin.
• Serum creatinine \> 220 µmol/l
• Serum potassium \> 5.0 mmol/l
• Pregnancy
• Addison's disease
• MRI-incompatible (ferrous) sulphate prosthesis
• Claustrophobia (unable to tolerate MR environment)
• Concurrent use of phenytoin, carbamazepine, rifampicin or St. John's Wort (reduce efficacy of eplerenone).

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead

Study Sites (1)

Western Infirmary

Glasgow, Scotland, G11 6NT, United Kingdom

Location

Related Publications (11)

• 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. doi: 10.1056/NEJMoa030207. Epub 2003 Mar 31.

  PMID: 12668699 BACKGROUND

• Weir RA, Petrie CJ, Murphy CA, Clements S, Steedman T, Miller AM, McInnes IB, Squire IB, Ng LL, Dargie HJ, McMurray JJ. Galectin-3 and cardiac function in survivors of acute myocardial infarction. Circ Heart Fail. 2013 May;6(3):492-8. doi: 10.1161/CIRCHEARTFAILURE.112.000146. Epub 2013 Mar 15.

  PMID: 23505301 DERIVED

• Weir RA, Tsorlalis IK, Steedman T, Dargie HJ, Fraser R, McMurray JJ, Connell JM. Aldosterone and cortisol predict medium-term left ventricular remodelling following myocardial infarction. Eur J Heart Fail. 2011 Dec;13(12):1305-13. doi: 10.1093/eurjhf/hfr129. Epub 2011 Sep 22.

  PMID: 21940729 DERIVED

• Weir RA, Clements S, Steedman T, Dargie HJ, McMurray JJ, Squire IB, Ng LL. Plasma TIMP-4 predicts left ventricular remodeling after acute myocardial infarction. J Card Fail. 2011 Jun;17(6):465-71. doi: 10.1016/j.cardfail.2011.02.002. Epub 2011 Mar 25.

  PMID: 21624734 DERIVED

• Weir RA, Murphy CA, Petrie CJ, Martin TN, Balmain S, Clements S, Steedman T, Wagner GS, Dargie HJ, McMurray JJ. Microvascular obstruction remains a portent of adverse remodeling in optimally treated patients with left ventricular systolic dysfunction after acute myocardial infarction. Circ Cardiovasc Imaging. 2010 Jul;3(4):360-7. doi: 10.1161/CIRCIMAGING.109.897439. Epub 2010 Mar 26.

  PMID: 20348438 DERIVED

• Weir RA, Miller AM, Murphy GE, Clements S, Steedman T, Connell JM, McInnes IB, Dargie HJ, McMurray JJ. Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction. J Am Coll Cardiol. 2010 Jan 19;55(3):243-50. doi: 10.1016/j.jacc.2009.08.047.

  PMID: 20117403 DERIVED

• Weir RA, Martin TN, Murphy CA, Petrie CJ, Clements S, Steedman T, Dargie HJ, Wagner GS. Comparison of serial measurements of infarct size and left ventricular ejection fraction by contrast-enhanced cardiac magnetic resonance imaging and electrocardiographic QRS scoring in reperfused anterior ST-elevation myocardial infarction. J Electrocardiol. 2010 May-Jun;43(3):230-6. doi: 10.1016/j.jelectrocard.2010.01.003. Epub 2010 Feb 1.

  PMID: 20116803 DERIVED

• Weir RA, Mark PB, Petrie CJ, Clements S, Steedman T, Ford I, Ng LL, Squire IB, Wagner GS, McMurray JJ, Dargie HJ. Left ventricular remodeling after acute myocardial infarction: does eplerenone have an effect? Am Heart J. 2009 Jun;157(6):1088-96. doi: 10.1016/j.ahj.2009.04.001.

  PMID: 19464421 DERIVED

• Iraqi W, Rossignol P, Angioi M, Fay R, Nuee J, Ketelslegers JM, Vincent J, Pitt B, Zannad F. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study. Circulation. 2009 May 12;119(18):2471-9. doi: 10.1161/CIRCULATIONAHA.108.809194. Epub 2009 Apr 27.

  PMID: 19398668 DERIVED

• Weir RA, Chong KS, Dalzell JR, Petrie CJ, Murphy CA, Steedman T, Mark PB, McDonagh TA, Dargie HJ, McMurray JJ. Plasma apelin concentration is depressed following acute myocardial infarction in man. Eur J Heart Fail. 2009 Jun;11(6):551-8. doi: 10.1093/eurjhf/hfp043. Epub 2009 Apr 6.

  PMID: 19351633 DERIVED

• Weir RA, Martin TN, Petrie CJ, Murphy A, Clements S, Steedman T, Wagner GS, McMurray JJ, Dargie HJ. Cardiac and extracardiac abnormalities detected by cardiac magnetic resonance in a post-myocardial infarction cohort. Cardiology. 2009;113(1):1-8. doi: 10.1159/000161233. Epub 2008 Oct 10.

  PMID: 18849604 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Ventricular Dysfunction, Left

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Robin AP Weir, MBChB, BSc, MRCP

  NHS Greater Glasgow and Clyde

  PRINCIPAL INVESTIGATOR

• Henry J Dargie, MBChB,FRCP

  NHS Greater Glasgow and Clyde

  STUDY DIRECTOR

• John JV McMurray, FRCP,MD,FESC

  University of Glasgow

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 18, 2005
• First Posted: August 19, 2005
• Study Start: April 1, 2005
• Last Updated: April 10, 2006

Record last verified: 2004-11

Locations

GB (1)