Verify the efficacy of early administration of eplerenone in relation to the development of pathological remodeling of the myocardium in patients after myocardial infarction.
Conditions
Interventions
Trade Name: EPLERENON SANDOZ 50mg
Product Name: EPLERENON SANDOZ 50 MG
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Trade N
Sponsors
IKEM
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. At least 18 years old 2. Have an ischemic symptom of >20 min within 24 hours before randomization 3. At least one of the following indicator of AMI: · ST-segment elevation =0.2 mV in at least 2 contiguous precordial leads · ST-segment elevation =0.1 mV in at least 2 contiguous limb leads · New or undated left bundle branch block · Q waves in at least 2 contiguous precordial leads (excluding V1 and avr) not known to be old · Troponin levels =3 times the upper local limit of normal and in case of NSTEMI, a Thrombolysis In Myocardial Infarction19 score =3 4. Written informed consent provided by the patient Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: • Cardiopulmonary instability • Killip score=3 • persistent atrial fibrillation with planned rate control therapy • serum creatinine> 220 umol / L for men and> 177 umol / L for women • serum potassium> 5.0 mmol / L • anticipated early aorto-coronary bypass or valve surgery • anticipated early pacemaker implantation or cardioverter-defibrillator • contraindications to perform MR (implanted pacemaker, defibrillator, or neurostimulator; the presence of foreign material in the body of uncertain origin or with known incompatibility with MR tomograph; implantation of coronary stents other than the Promus Element-Boston Scientific, Orsiro-Biotronic, RESOLUT Integrity Medtronic; extreme overweight; the claustrophobia) • age <18 years • pregnancy, lactation • premenopausal women who are not willing to use an effective form of contraception • absence of consent to inclusion in the study • clinically relevant polymorbidity • assumption noncompliance • Hypersensitivity to the active substance or to any of the excipients • Patients with moderate to severe renal insufficiency (creatinine clearance <50 ml / min or serum creatinine levels above 220 umol / L in men and over 170 umol / L in women • Patients with severe hepatic insufficiency (class C according to Child-Pugh). • Patients receiving potassium-sparing diuretics, potassium supplements or strong inhibitors of CYP3A4 (eg. Itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone) • Simultaneous treatment of mild to moderate CYP3A4 inhibitors, eg. Amiodarone, diltiazem and verapamil • diagnosing heart failure in the past • In the past identified LV EF below 40%
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: With use of cardiac magnetic resonance (CMR) demonstrate the benefit of early treatment with eplerenone in reducing pathological remodeling of the left ventricle (LV) in patients with acute myocardial infarction (AMI).;Secondary Objective: Pathological remodeling factors, such as a serum biomarker or indirect indicators arrhythmogenesis In relation to active treatment with eplerenone will be studied.;Primary end point(s): The effect of early administration of eplerenone will lead to: • Reduction of the LV fibrosis assessed by CMR method MOLLI • Influence of LVEDV, LVESV, EF asssessed by MR • Decrease of the serum concentration of galectin-3 • Reduction of ventricular ectopic assessed by 24 h ECG Holter Predictive factor for LV pathological remodeling is: • The rate of early microvascular obstruction assessed by MRI;Timepoint(s) of evaluation of this end point: Ambulatory monitoring in the 1st and 6th month • Standard 12-lead ECG during AMI, before the discharge of the patient at the end of the first week after AMI, in the 1st and 6th month • Left ventriculography performed during acute coronary angiography • Echocardiographic examination within 48 hours of AMI (in case that left ventriculography is not performed, echocardiographic examination will be performed before randomization), before discharge of the patient at the end of the first week after AMI and at 6 months •CMRduring the first week of AMI (minimum 96 hours after AMI) and at 6 months • Serum biomarkers (BNP, Galectin-3, cortisol, aldosterone, plasma renin activity) - before randomization, before discharge, as well as in the 1st and 6th month | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The effect of early administration of eplerenone will lead to: • Decline in serum concentrations of BNP • Shortening of QRS interval duration • Favorable impact on ECG markers related to arrhythmogenesis Predictive factors for LV pathological remodeling LK are: • The period of ischemia • The size of infarct on assessed on initial MRI scans;Timepoint(s) of evaluation of this end point: •Signal-averaged ECG in the first week of AIM (at least 72 hours after AMI) and at 6 months • Ultra-high-frequency (UHF) ECG in the first week after AIM (at least 72 hours after AIM) and at 6 months • ECG Holter / 24 hours in the first week after AMI (at least 72 hours after AMI) and at 6 months • Consumption levels of troponin T (hsTnT) - during AMI, 8 hours and 48 hours after AMI, in the 1st and 6th month • Iontogram (K +, Na +, Cl-), urea, creatinine - before randomization, every day during hospitalization for AMI, in the 1st, 3rd and 6th month • Blood pressure measurement during AMI, then daily during the stay in the intensive care unit, in the 1st and 6th month • A pregnancy test prior to enrollment • Objectified drug compliance in the 6th month | — |
Countries
Czech Republic
Contacts
Public ContactALES HERMAN
IKEM
Outcome results
None listed