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Completed

NCT Number: NCT01882179

Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size

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.

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Key information

Conditions

ST-elevation Myocardial Infarction Cardiovascular Diseases Heart Diseases Infarction Ischemia Myocardial Infarction Myocardial Ischemia Necrosis Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Reperfusion Injury ST Elevation Myocardial Infarction Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Cardiothoracic Center - Basildon and Thurrock University Hospitals, Basildon, Essex, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Mineralocorticoid receptor antagonist potassium-canrenoate

Drug

Placebo

Drug

Primary outcomes

  1. Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging

    Time frame: 12 weeks after STEMI

Secondary outcomes

  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

Sponsors and collaborators

Lead sponsor

University College, London

Other

Collaborators

  • British Heart Foundation

Registry information

Official study title

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

Acronym: MINIMISE-STEMI

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Jun 20, 2013
Registry last updated
Oct 26, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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