Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size
Information source: University College, London
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: ST-elevation Myocardial Infarction
Intervention: Mineralocorticoid receptor antagonist potassium-canrenoate (Drug); placebo (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: University College, London Official(s) and/or principal investigator(s): Derek J Hausenloy, PhD, Study Director, Affiliation: University College London, Hatter Cardiovascular Institute Georg M Fröhlich, MD, Study Chair, Affiliation: University College London, The Heart Hospital Pascal Meier, MD, Principal Investigator, Affiliation: University College London, The Heart Hospital Reto Gamma, MD, Principal Investigator, Affiliation: Basildon and Thurrock University Hospitals Anthony Mathur, PhD, Principal Investigator, Affiliation: London Chest Hospital John Greenwood, MD, Principal Investigator, Affiliation: Leeds General Infirmary
Overall contact: Derek J Hausenloy, PhD, Phone: +44 (0) 203 447 9888, Email: d.hausenloy@ucl.ac.uk
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.
Clinical Details
Official title: MINeralocorticoid Receptor Antagonist Pretreatment to MINIMISE Reperfusion Injury After ST-Elevation Myocardial Infarction (STEMI)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging
Secondary outcome: Markers of myocardial reperfusion injuryMicrovascular obstruction on cardiac MRI Myocardial salvage Acute myocardial infarct size LV remodelling Clinical outcome measures
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Derek J Hausenloy, PhD, Phone: +44 (0) 203 447 9888, Email: d.hausenloy@ucl.ac.uk
Leeds Genereal Infirmary, Leeds, United Kingdom; Recruiting John Greenwood, MD, Email: J.Greenwood@leeds.ac.uk
Heart Hospital London, London W1G 8PH, United Kingdom; Recruiting Alex Sirker, MD, Email: Alex.Sirker@uclh.nhs.uk Alex Sirker, MD, Principal Investigator
London Chest Hospital, London E2 9JX, United Kingdom; Recruiting Anthony Mathur, PhD, Email: Emma.Bastian@bartshealth.nhs.uk Anthony Mathur, PhD, Principal Investigator
Cardiothoracic Center - Basildon and Thurrock University Hospitals, Basildon, Essex SS16 5NL, United Kingdom; Recruiting Reto Gamma, MD, Email: retogamma@nhs.net Reto Gamma, MD, Principal Investigator
Additional Information
Related publications: Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309-21. Epub 2003 Mar 31. Erratum in: N Engl J Med. 2003 May 29;348(22):2271. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011 Jan 6;364(1):11-21. doi: 10.1056/NEJMoa1009492. Epub 2010 Nov 14. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. Schmidt K, Tissier R, Ghaleh B, Drogies T, Felix SB, Krieg T. Cardioprotective effects of mineralocorticoid receptor antagonists at reperfusion. Eur Heart J. 2010 Jul;31(13):1655-62. doi: 10.1093/eurheartj/ehp555. Epub 2009 Dec 21.
Starting date: November 2013
Last updated: January 29, 2015
|