Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size

Summary

Heart attacks, or myocardial infarcts, are a major cause of death and disability in the UK. Immediate unblocking of the obstructed heart vessel with a balloon catheter and implantation of a mesh scaffold (stent) in heart centers is warranted in these patients. Morbidity and mortality in this patient group is related to the infarct size. Therefore, there is a need to discover novel therapeutic agents which reduce myocardial infarct size and preserve the contractile heart function.

Large trials involving several thousand patients have demonstrated a survival benefit in patients with impaired heart function due to a heart attack, who received a mineralo-corticoid receptor antagonist (MRA, drug name: spironolactone). In these trials patients received the drug late, 3-14 days after the heart attack.

Our proposal is to investigate whether MRA therapy administered intravenously prior to unblocking an occluded heart vessel, can reduce infarct size and as such can prevent long term sequelae of heart attacks.

150 patients admitted to 4 tertiary care hospitals (Heart Hospital London, London Chest, Essex Cardiothoracic Center and Leeds General Infirmary) for heart attack will be randomly assigned to receive MRA treatment or placebo. The first dose of the MRA will be applied intravenously immediately in the catheter suite, even before re-opening of the occluded vessel. From the second day on, patients will be prescribed oral MRA treatment, as a pill, for a total of three months. Before hospital discharge and after three months, a magnetic resonance image (MRI) of the heart will accurately investigate the evolution of infarct (scar) size and the contractile heart function and compare the group of patients who received the MRA drug versus the placebo control group. Of note, patients with an ejection fraction \<40% AND signs of heart failure OR diabetes will go on open label eplerenone according to current guidelines, instead of the study drug.

This study will give first evidence, if very early MRA treatment improves heart function and should be used as early as possible for treatment of patients after a heart attack.

Conditions

• ST-elevation Myocardial Infarction

Interventions

DRUG

Mineralocorticoid receptor antagonist potassium-canrenoate

DRUG

placebo

Sponsors & Collaborators

• British Heart Foundation

  collaborator OTHER

• University College, London

  lead OTHER

Principal Investigators

• Derek J Hausenloy, PhD · University College London, Hatter Cardiovascular Institute

• Georg M Fröhlich, MD · University College London, The Heart Hospital

• Pascal Meier, MD · University College London, The Heart Hospital

• Reto Gamma, MD · Basildon and Thurrock University Hospitals

• Anthony Mathur, PhD · London Chest Hospital

• John Greenwood, MD · Leeds General Infirmary

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-11-30

Primary Completion

2016-05-31

Completion

2016-05-31

Countries

• United Kingdom

Study Locations