E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 2 diabetes mellitus and heart failure of ischemic origin |
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E.1.1.1 | Medical condition in easily understood language |
Patients with diabetes and heart failure |
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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 hypothesis that empagliflozin (Jardiance™) 25 mg once daily for four months improves myocardial function, structure and coronary flow reserve measured by means of cardiac magnetic resonance in patients with T2DM and HF of ischemic origin. |
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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. Known T2DM (according to current WHO criteria) with HbA1c 48-86 mmol/mol (DCCT 5.6-10%; [57]).
3. Chronic HF of ischemic origin (established according to current European Guidelines; Ischemic etiology defined as history of myocardial infarction given by typical ECG-changes (Q-wave or LBBB), previous PCI or CABG, symptoms typical of angina pectoris with coronary artery disease verified by an exercise test, non-invasive imaging or coronary angiography, since at least two months [58].
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. Age > 75 years
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 important 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) or chronic HF due to valvular disorders.
6. Patients who, in the opinion of the investigator, will have difficulties to comply with the protocol (examples: problems to self-monitor glucose, linguistic problems, resident outside of the catchment area, alcohol or drug abuse, psychiatric disorder)
7. Planned for intervention with at discharge are planned for Coronary Artery Bypass Grafting, Percutaneous Coronary Intervention or cardiac device treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints are
1. Improvement in LV systolic and diastolic function (an increase in LV ejection fraction, a reduction in LV filling pressures and a decrease in the LV end diastolic volume) measured by cardiovascular magnetic resonance (CMR) and echocardiography
2. An increase in coronary flow reserve measured by rest/adenosine coronary sinus phase contrast flow and rest/adenosine quantitative first pass myocardial perfusion
3. Decrease in the left ventricular end-diastolic volume and myocardial extracellular volume (ECV)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 4 months on active treatment |
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E.5.2 | Secondary end point(s) |
1. Reduction in the NT-pro BNP levels
2. Changes in blood volume evaluated by Hematocrit, Hb and radiolabelled albumin
3. Improvement in endothelial function
4. Decrease in arterial stiffness
5. Reduction of expressions of inflammatory activation and oxidative stress
6. Hospitalizations for HF
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 4 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 five months after randomization and the final month is off test drug in order to establish if any favorable effects of empagliflozin are long-lasting or vanishes with drug cessation |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |