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.
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Inclusion criteria for entry into trial
Patients >18 years
Patients presenting with acute STEMI (as assessed by 12 lead ECG; ST segment elevation ≥2 mm (0.2 mV) in 2 or more contiguous precordial leads or ≥1mm (0.1mm) in 2 or more adjacent limb leads).
Presentation within 12 hours after symptom onset
Inclusion criteria for randomization (assessed in catheter laboratory)
Angiographically proven proximal occlusion (TIMI 0) of a major coronary vessel (LAD, LCX, RCA).
Normal potassium (<5.0 mmol/l)
Patients with known LVEF ≤40%
Participation in another trial
Cardiogenic shock (positive shock index OR need for catecholamine support OR systolic blood pressure < 90 mmHg)
Killip class > 2
Prior myocardial infarction
Known compromised renal function (eGFR < 30 ml/min/1.73 m2) or potassium > 5.0 mmol/l
Current treatment with mineralocorticoid receptor antagonists
Pregnant or lactating females
Allergies to IMP or its excipients
Known contraindication to cardiac magnetic resonance imaging (MRI) such as significant claustrophobia, severe allergy to gadolinium chelate contrast, , presence of MRI contraindicated implanted devices (eg, pacemaker, implanted cardiac defibrillator, cardiac resynchronization therapy device, cochlear implant), imbedded metal objects (eg, shrapnel), or any other contraindication for cardiac MRI.
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01882179
Contact: Derek J Hausenloy, PhD +44 (0) 203 447 9888 firstname.lastname@example.org
Contact: Georg M Fröhlich, MD ++44 79 640 958 38 email@example.com
Cardiothoracic Center – Basildon and Thurrock University Hospitals Recruiting
Basildon, Essex, United Kingdom, SS16 5NL
Contact: Reto Gamma, MD firstname.lastname@example.org
Principal Investigator: Reto Gamma, MD
Leeds Genereal Infirmary Recruiting
Leeds, United Kingdom
Contact: John Greenwood, MD J.Greenwood@leeds.ac.uk
Heart Hospital London Recruiting
London, United Kingdom, W1G 8PH
Contact: Alex Sirker, MD Alex.Sirker@uclh.nhs.uk
Principal Investigator: Alex Sirker, MD
London Chest Hospital Recruiting
London, United Kingdom, E2 9JX
Contact: Anthony Mathur, PhD Emma.Bastian@bartshealth.nhs.uk
Principal Investigator: Anthony Mathur, PhD