E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Cardiovascular disease refers to any disease that affects the cardiovascular system, principally cardiac disease,vascular diseases of the brain and kidney, and peripheral arterial disease. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007649 |
E.1.2 | Term | Cardiovascular disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does the administration of mineralo-corticoid-receptor antagonist (MRA) therapy initiated prior to coronary angioplasty followed by three months MRA therapy reduced the damage to the heart muscle in patients presenting with a heart attack? |
|
E.2.2 | Secondary objectives of the trial |
Secondary endpoints: 1.Several markers of myocardial reperfusion injury angiographical scores, successfull blood flow restoration post angioplasty, resolution of ECG changes after balloon angioplasty) 2.early changes in the heart muscle, as assessed with cardiac MRI 3.Measurement of acute myocardial infarct size (blood markers and cardiac MRI on day 3) 5.Heart size and function on 3 month cardiac MRI scan 6.Clinical outcome measures: cardiovascular death, non-fatal myocardial infarction, for heart failure, hyperkalemia, deterioration of kidney function, need for dialysis. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•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 •Angiographically proven proximal occlusion (TIMI 0) of a major coronary vessel (LAD, LCX, RCA). |
|
E.4 | Principal exclusion criteria |
•Patients with known LVEF ≤40% prior to randomisation •Cardiogenic shock (catecholamine support OR systolic blood pressure < 90 mmHg) •Killip class > 2 •Prior myocardial infarction •Potassium > 5.0 mmol/l or known renal failure (> CKD III) or porphyria •known impaired liver function or liver failure •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, severe renal insufficiency (defined as an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2, known from previous examinations), 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 Once the current serum creatinine is known, patients with severely compromised renal function (eGFR < 30 ml/min/1.73 m2) will also be excluded. Patients with known porphyria. Patients with significant liver dysfunction (INR>2). Patients with known contraindications to treatment with spironolactone. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Myocardial infarct (scar) size 3 months after a heart attack, as assessed with CMR. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Myocardial infarct (MI) size, as assessed by cardiac magnetic resonance imaging 12 weeks after an acute STEMI. |
|
E.5.2 | Secondary end point(s) |
In the case of secondary endpoint Fisher’s exact test is used to compare categorical variables. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuous variables will be compared with a mixed effects model to account for repeated measures. Time-to-event analyses (secondary clinical endpoints), based on all available follow-up data, will be performed with the use of Kaplan–Meier estimates and be compared between groups with the use of the log-rank test. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 29 |