Early Mineralocorticoid Receptor Antagonist Treatment to Reduce Myocardial Infarct Size
NCT ID: NCT01882179
Last Updated: 2016-10-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
61 participants
INTERVENTIONAL
2013-11-30
2016-05-31
Brief Summary
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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.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Placebo
Intravenous saline bolus prior to PPCI followed by oral placebo for 3 months
placebo
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.
Mineralocorticoid receptor antagonist potassium-canrenoate
Interventions
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Mineralocorticoid receptor antagonist potassium-canrenoate
placebo
Eligibility Criteria
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Inclusion Criteria
* 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
* Angiographically proven proximal occlusion (TIMI 0) of a major coronary vessel (LAD, LCX, RCA).
* Normal potassium (\<5.0 mmol/l)
Exclusion Criteria
* 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.
18 Years
ALL
No
Sponsors
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British Heart Foundation
OTHER
University College, London
OTHER
Responsible Party
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Principal Investigators
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Derek J Hausenloy, PhD
Role: STUDY_DIRECTOR
University College London, Hatter Cardiovascular Institute
Georg M Fröhlich, MD
Role: STUDY_CHAIR
University College London, The Heart Hospital
Pascal Meier, MD
Role: PRINCIPAL_INVESTIGATOR
University College London, The Heart Hospital
Reto Gamma, MD
Role: PRINCIPAL_INVESTIGATOR
Basildon and Thurrock University Hospitals
Anthony Mathur, PhD
Role: PRINCIPAL_INVESTIGATOR
London Chest Hospital
John Greenwood, MD
Role: PRINCIPAL_INVESTIGATOR
Leeds General Infirmary
Locations
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Cardiothoracic Center - Basildon and Thurrock University Hospitals
Basildon, Essex, United Kingdom
London Chest Hospital
London, London, United Kingdom
Heart Hospital London
London, London, United Kingdom
Leeds Genereal Infirmary
Leeds, , United Kingdom
Countries
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References
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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. doi: 10.1056/NEJMoa030207. Epub 2003 Mar 31.
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. doi: 10.1056/NEJM199909023411001.
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.
Other Identifiers
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12/0533
Identifier Type: -
Identifier Source: org_study_id