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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University College, London
Sponsor:
Collaborators:
Rosetrees Trust
Heart Hospital Charity Fund
Hatter Cardiovascular Institute Trustees
British Heart Foundation
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01882179
First received: June 17, 2013
Last updated: December 2, 2013
Last verified: November 2013

June 17, 2013
December 2, 2013
November 2013
November 2014   (final data collection date for primary outcome measure)
Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging [ Time Frame: 12 weeks after STEMI ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01882179 on ClinicalTrials.gov Archive Site
  • 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
  • Markers of myocardial reperfusion injury [ Time Frame: within 90 min post PCI ] [ Designated as safety issue: No ]
    Myocardial blush grade, TIMI flow post-PPCI, ST-segment resolution at 90 min 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: 3 days ] [ Designated as safety issue: No ]
    serum biomarkers: hsTnT, CK-MB and NT-proBNP, hsCrP and cardiac MRI on day 3: 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
Not Provided
Not Provided
 
Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size
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 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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
ST-elevation Myocardial Infarction
  • Drug: Mineralocorticoid receptor antagonist potassium-canrenoate
  • Drug: placebo
  • Placebo Comparator: Placebo
    Intravenous saline bolus prior to PPCI followed by oral placebo for 3 months
    Intervention: 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.

    Intervention: Drug: Mineralocorticoid receptor antagonist potassium-canrenoate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
March 2015
November 2014   (final data collection date for primary outcome measure)

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 theatre)

  • 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.
Both
18 Years and older
No
Contact: Derek J Hausenloy, PhD +44 (0) 203 447 9894 d.hausenloy@ucl.ac.uk
Contact: Georg M Fröhlich, MD ++44 79 640 958 38 georg.froehlich@gmx.at
United Kingdom
 
NCT01882179
12/0533
Yes
University College, London
University College, London
  • Rosetrees Trust
  • Heart Hospital Charity Fund
  • Hatter Cardiovascular Institute Trustees
  • British Heart Foundation
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
University College, London
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP