Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size (MINIMISE STEMI)
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 3 tertiary care hospitals (Heart Hospital London, London Chest, Essex Cardiothoracic Center Basildon) 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.
ST-elevation Myocardial Infarction
Drug: Mineralocorticoid receptor antagonist potassium-canrenoate
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (STEMI)|
- Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging [ Time Frame: 12 weeks after STEMI ] [ Designated as safety issue: No ]
- Markers of myocardial reperfusion injury [ Time Frame: 48 hours ] [ Designated as safety issue: No ]TIMI flow post-PPCI, ST-segment resolution post-PPCI
- Microvascular obstruction on cardiac MRI [ Time Frame: 0-6 days after STEMI ] [ Designated as safety issue: No ]hypodense area of late gadolinium enhancement
- Myocardial salvage [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Area at risk assessed by T2 weighted imaging subtract final MI size
- Acute myocardial infarct size [ Time Frame: 2-6 days ] [ Designated as safety issue: No ]serum biomarkers: hsTnT, CK-MB, CK and cardiac MRI: late gadolinium enhancement
- LV remodelling [ Time Frame: 12 week cardiac MRI scan ] [ Designated as safety issue: No ]LV end-diastolic and end-systolic volumes, LV ejection fraction, LV mass and wall-thickness
- Clinical outcome measures [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]cardiovascular death, non-fatal myocardial infarction, revascularisation, hospitalisation for heart failure, hyperkalemia, deterioration of kidney function, need for dialysis
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Intravenous saline bolus prior to PPCI followed by oral placebo for 3 months
Active Comparator: Mineralocorticoid receptor antagonist
1st dose (day 0) given i.v. (potassium-canrenoate), before primary PCI day 1 - 12 weeks: spironolactone 25mg daily, which is uptitrated to 50mg daily after 2 weeks, if possible
In case the LVEF <40% on baseline MRI and the patient shows signs of heart failure or is diabetic, the patient will receive open label eplerenone instead of the study drug, according to current guidelines.
|Drug: Mineralocorticoid receptor antagonist potassium-canrenoate|
|Contact: Derek J Hausenloy, PhD||+44 (0) 203 447 firstname.lastname@example.org|
|Contact: Georg M Fröhlich, MD||++44 79 640 958 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|
|Heart Hospital London||Not yet recruiting|
|London, United Kingdom, W1G 8PH|
|Contact: Pascal Meier, MD email@example.com|
|Principal Investigator: Pascal Meier, MD|
|London Chest Hospital||Not yet recruiting|
|London, United Kingdom, E2 9JX|
|Contact: Anthony Mathur, PhD Emma.Bastian@bartshealth.nhs.uk|
|Principal Investigator: Anthony Mathur, PhD|
|Study Director:||Derek J Hausenloy, PhD||University College London, Hatter Cardiovascular Institute|
|Study Chair:||Georg M Fröhlich, MD||University College London, The Heart Hospital|
|Principal Investigator:||Pascal Meier, MD||University College London, The Heart Hospital|
|Principal Investigator:||Reto Gamma, MD||Basildon and Thurrock University Hospitals|
|Principal Investigator:||Anthony Mathur, PhD||London Chest Hospital|