COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size (MINIMISE-STEMI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01882179
Recruitment Status : Completed
First Posted : June 20, 2013
Last Update Posted : October 26, 2016
British Heart Foundation
Information provided by (Responsible Party):
University College, London

Brief 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.

Condition or disease Intervention/treatment Phase
ST-elevation Myocardial Infarction Drug: Mineralocorticoid receptor antagonist potassium-canrenoate Drug: placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (STEMI)
Study Start Date : November 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Intravenous saline bolus prior to PPCI followed by oral placebo for 3 months
Drug: placebo
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

Primary Outcome Measures :
  1. Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging [ Time Frame: 12 weeks after STEMI ]

Secondary Outcome Measures :
  1. Markers of myocardial reperfusion injury [ Time Frame: 48 hours ]
    TIMI flow post-PPCI, ST-segment resolution post-PPCI

  2. Microvascular obstruction on cardiac MRI [ Time Frame: 1-3 days after STEMI ]
    hypodense area of late gadolinium enhancement

  3. Myocardial salvage [ Time Frame: 12 weeks ]
    Area at risk assessed by T2 weighted imaging subtract final MI size

  4. Acute myocardial infarct size [ Time Frame: 1-3 days ]
    serum biomarkers: hsTnT, CK-MB, CK and cardiac MRI: late gadolinium enhancement

  5. LV remodelling [ Time Frame: 12 week cardiac MRI scan ]
    LV end-diastolic and end-systolic volumes, LV ejection fraction, LV mass and wall-thickness

  6. Clinical outcome measures [ Time Frame: 12 weeks ]
    cardiovascular death, non-fatal myocardial infarction, revascularisation, hospitalisation for heart failure, hyperkalemia, deterioration of kidney function, need for dialysis

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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)

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01882179

Layout table for location information
United Kingdom
Cardiothoracic Center - Basildon and Thurrock University Hospitals
Basildon, Essex, United Kingdom, SS16 5NL
Leeds Genereal Infirmary
Leeds, United Kingdom
London Chest Hospital
London, United Kingdom, E2 9JX
Heart Hospital London
London, United Kingdom, W1G 8PH
Sponsors and Collaborators
University College, London
British Heart Foundation
Layout table for investigator information
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
Principal Investigator: John Greenwood, MD Leeds General Infirmary
Layout table for additonal information
Responsible Party: University College, London Identifier: NCT01882179    
Other Study ID Numbers: 12/0533
First Posted: June 20, 2013    Key Record Dates
Last Update Posted: October 26, 2016
Last Verified: May 2016
Keywords provided by University College, London:
Reperfusion injury
myocardial infarct size
Additional relevant MeSH terms:
Layout table for MeSH terms
Myocardial Infarction
ST Elevation Myocardial Infarction
Reperfusion Injury
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Postoperative Complications
Canrenoic Acid
Mineralocorticoid Receptor Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Hormone Antagonists
Diuretics, Potassium Sparing
Natriuretic Agents