E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with acute coronary syndromes (myocardial infarction or unstable angina pectoris) with newly detected glucose perturbations (impaired glucose tolerance or type 2 diabetes) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with a recent heart attack and abnormal glucose metabolism |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
To test the hypotheses that Empagliflozin (Jardiance®) will have a beneficial effect on myocardial function and structure, glucose homeostasis and beta cell function in patients with recent myocardial infarction or unstable angina pectoris and newly detected impaired glucose tolerance or type 2 diabetes. |
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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 |
1. Age >18 years
2. Acute myocardial infarction or unstable angina pectoris according to the joint ESC and ACC recommendations [46]. This event should have occurred during the previous six months.
3. Newly detected impaired glucose tolerance (IGT) or type 2 diabetes (T2DM) revealed by an oral glucose tolerance test (OGTT) according to WHO [47].
4. Signed informed consent to trial participation consistent with ICH-GCP guidelines and local legislations.
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E.4 | Principal exclusion criteria |
1. Previously known diabetes (type 1 or 2).
2. Contraindications to magnetic resonance imaging
a) Implanted devices such as pacemaker or implantable cardioverter defibrillator
b) Severe claustrophobia
3. Serum creatinine estimated glomerular filtration rate < 30 ml/min/1.73m2.
4. Intolerance or contraindications to iv. adenosine infusion, including clinically known asthma. Patients with chronic obstructive pulmonary disease (COPD) should have a lung function test with reversibility testing performed within 12 month before study inclusion. The patient can be included if FEV1.0 is >60% of expected normal value and the reversibility test result should be <10% of the initial FEV1.0 value.
5. Patients with severe concomitant disease (i.e. malignancy, liver failure).
6. Patients who at discharge are planned for Coronary Artery Bypass Grafting or Percutaneous Coronary Intervention.
7. Congestive heart failure (NYHA III-IV).
8. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.
9. Patients who, in the opinion of the investigator, will have difficulties to comply with the protocol (examples: resident outside of the catchment area, linguistic reasons, alcohol or drug abuse, psychiatric disorder,).
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Changes in cardiovascular magnetic resonance (CMR) measures
a) Decrease in
i) Left ventricular end-diastolic volume
ii) Myocardial extracellular volume fraction (ECV) in non-infarcted (remote)
myocardium
b) Increase in
i) Coronary flow reserve measured by
rest/adenosine coronary sinus phase contrast flow measurement
rest/adenosine quantitative first pass myocardial perfusion
2. An improvement in beta-cell function after four months treatment measured by means of
insulinogenic index (ΔI30/ΔG30) obtained from an OGTT.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After seven months on active treatment |
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E.5.2 | Secondary end point(s) |
1. Improvement in systolic and diastolic left ventricular function and mass
2. Improvement of glucose tolerance tested with an OGTT.
3. Improvement in endothelial function
4. Decreased arterial stiffness
5. Reduction of expressions for inflammatory activation and oxidative stress
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After seven months on active treatment |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
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The trial ends for each patient ten months after randomization and the final three months is off test drug in order to establish if any favorable effects of empagliflozin are long-lasting or vanishes with the cessation of drug administration. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |