E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial Infarction |
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E.1.1.1 | Medical condition in easily understood language |
Heart attack (myocardial infarction) |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
The main objective of this event-driven trial is to demonstrate the superiority of empagliflozin 10 mg once daily versus placebo, in addition to standard of care, for the reduction of the composite endpoint of time to first heart failure hospitalisation or all-cause mortality in high-risk patients hospitalised for acute MI. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial • Diagnosis of acute MI (type 1 per the Universal Definition of Myocardial Infarction [R20-0005]): STEMI or NSTEMI with randomisation to occur no later than 14 calendar days after hospital admission. For patients with an in-hospital MI as qualifying event, randomisation must still occur within 14 days of hospital admission. • High risk of HF, defined as EITHER a) Symptoms (e.g. dyspnea; decreased exercise tolerance; fatigue), or signs of congestion (e.g. pulmonary rales, crackles or crepitations; elevated jugular venous pressure; congestion on chest X-ray), that require treatment (e.g. augmentation or initiation of oral diuretic therapy; i.v. diuretic therapy; i.v. vasoactive agent; mechanical intervention etc.) at any time during the hospitalisation. OR b) Newly developed LVEF < 45% as measured by echocardiography, ventriculography, cardiac CT, MRI or radionuclide imaging during index hospitalisation. In addition at least one of the following risk factors: - Age > 65 years - Newly developed LVEF < 35% - Prior MI (before index MI) documented in medical records - eGFR < 60 ml/min/1.73m2 (according to creatinine from most recent local lab during the index hospitalisation and calculated with the CKD-EPI formula) - Atrial fibrillation (persistent or permanent ; if paroxysmal, only valid if associated with index MI) - Type 2 diabetes mellitus (prior or new diagnosis) - NTproBNP >1,400 pg/mL for patients in sinus rhythm, >2,800 pg/mL if atrial fibrillation; BNP >350 pg/mL for patients in sinus rhythm, >700 pg/mL if atrial fibrillation, measured at any time during hospitalisation - Uric acid >7.5 mg/dL (>446 μmol/L), measured at any time during hospitalisation - Pulmonary Artery Systolic Pressure >40 mmHg (non-invasive [usually obtained from clinically indicated post-MI echocardiography] or invasive, at any time during hospitalisation) - Patient not revascularized (and no planned revascularization) for the index MI (Includes e.g. patients where no angiography is performed, unsuccessful revascularization attempts, diffuse atherosclerosis not amenable for intervention; but does NOT include if revascularization was not performed due to nonobstructive coronary arteries) - 3-vessel coronary artery disease at time of index MI - Diagnosis of peripheral artery disease (extracoronary vascular disease, e.g. lower extremity artery disease or carotid artery disease) |
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E.4 | Principal exclusion criteria |
• Diagnosis of chronic HF prior to index MI • Systolic blood pressure < 90 mmHg at randomisation • Cardiogenic shock or use of i.v. inotropes in last 24 hours before randomisation • Coronary Artery Bypass Grafting planned at time of randomisation • Current diagnosis of Takotsubo cardiomyopathy • Any current severe (stenotic or regurgitant) valvular heart disease • eGFR < 20 ml/min/1.73m2 (using CKD-EPI formula based on most recent creatinine from local lab during hospitalisation) or on dialysis • Type I diabetes mellitus • History of ketoacidosis |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Composite of time to first HHF or all-cause mortality
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From the day of first randomization until the total number of patients with investigator reported primary endpoint events reaches a target of 532. |
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E.5.2 | Secondary end point(s) |
• Total number of HHF or all-cause mortality • Total number of non-elective CV hospitalization or all-cause mortality • Total number of non-elective all-cause hospitalisation or all-cause mortality • Total number of hospitalisation for MI or all-cause mortality |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From the day of first randomization until the total number of patients with investigator reported primary endpoint events reaches a target of 532. |
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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 | Yes |
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) | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 159 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
China |
India |
Israel |
Korea, Democratic People's Republic of |
Mexico |
Russian Federation |
Serbia |
Ukraine |
United States |
Bulgaria |
Denmark |
France |
Germany |
Hungary |
Netherlands |
Poland |
Romania |
Spain |
Czechia |
Argentina |
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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
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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 | 16 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |