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

October 25, 2016 updated by: University College, London

MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (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 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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Leeds, United Kingdom
        • Leeds Genereal Infirmary
      • London, United Kingdom, E2 9JX
        • London Chest Hospital
      • London, United Kingdom, W1G 8PH
        • Heart Hospital London
    • Essex
      • Basildon, Essex, United Kingdom, SS16 5NL
        • Cardiothoracic Center - Basildon and Thurrock University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging
Time Frame: 12 weeks after STEMI
12 weeks after STEMI

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Markers of myocardial reperfusion injury
Time Frame: 48 hours
TIMI flow post-PPCI, ST-segment resolution post-PPCI
48 hours
Microvascular obstruction on cardiac MRI
Time Frame: 1-3 days after STEMI
hypodense area of late gadolinium enhancement
1-3 days after STEMI
Myocardial salvage
Time Frame: 12 weeks
Area at risk assessed by T2 weighted imaging subtract final MI size
12 weeks
Acute myocardial infarct size
Time Frame: 1-3 days
serum biomarkers: hsTnT, CK-MB, CK and cardiac MRI: late gadolinium enhancement
1-3 days
LV remodelling
Time Frame: 12 week cardiac MRI scan
LV end-diastolic and end-systolic volumes, LV ejection fraction, LV mass and wall-thickness
12 week cardiac MRI scan
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
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

British Heart Foundation

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

June 17, 2013

First Submitted That Met QC Criteria

June 19, 2013

First Posted (Estimate)

June 20, 2013

Study Record Updates

Last Update Posted (Estimate)

October 26, 2016

Last Update Submitted That Met QC Criteria

October 25, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12/0533

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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