E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obese patients (BMI >28 kg/m2), aged 60-84 years, with documented cardiovascular disease but no history of diabetes mellitus or heart failure with reduced ejection fraction. |
Overvægtige patienter (BMI >28 kg/m2), i alder 60-84 år, med dokumenteret kardiovaskulær sygdom, men uden kendt sukkersyge eller hjertesvigt med nedsat pumpefunktion. |
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E.1.1.1 | Medical condition in easily understood language |
Obese patients (BMI >28 kg/m2), aged 60-84 years, with documented cardiovascular disease but no history of diabetes mellitus or heart failure with reduced ejection fraction. |
Overvægtige patienter (BMI >28 kg/m2), i alder 60-84 år, med dokumenteret hjertekarsygdom, men uden kendt sukkersyge eller hjertesvigt med nedsat pumpefunktion. |
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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 |
Empire Prevent: Cardiac (1)To evaluate whether 6 months of treatment with 10 mg of Empagliflozin can improve peak oxygen consumption (VO2) in elderly and obese patients with cardiovascular disease.
(2) To evaluate whether 6 months of treatment with 10 mg of Empagliflozin can reduce left ventricular (LV) mass index in elderly and obese patients with cardiovascular disease
Empire Prevent: Metabolic (1)To evaluate whether 6 months of treatment with 10 mg of Empagliflozin can reduce estimated extracellular volume (eECV) in elderly and obese patients with cardiovascular disease.
(2) To evaluate whether 6 months of treatment with 10 mg of Empagliflozin can reduce epicardial adipose tissue (EAT) in elderly and obese patients with cardiovascular disease |
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E.2.2 | Secondary objectives of the trial |
Empire Prevent: Cardiac (1) To investigate whether the improvement in peak VO2 is associated with improvement in daily activity level measured by an accelerometer and self-reported quality of life.
(2) To evaluate whether reduction in LV mass is associated with reduction in cardiac fibrosis and left atrial maximal volume.
Empire Prevent: Metabolic (1) To evaluate whether the decrease in eECV is associated with a decrease in estimated plasma volume (ePV) and further, if these changes are accompanied by a reduction in s-urate and a stabilization of glomerular filtration rate.
(2) To evaluate whether reduction in EAT is associated with a reduction in pericardial adipose tissue
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Empire Prevent Cardiac: (1) To evaluate whether 6 months of treatment with 10 mg of Empagliflozin reduces ambulatory blood pressure and arterial vascular stiffness (Vascular function hypothesis)
(2) To evaluate whether 6 months treatment with 10mg of Empagliflozin reduces left atrial maximal and minimal volume (Cardiac remodeling hypothesis)
(3) To evaluate whether 6 months of treatment with 10 mg of Empagliflozin reduces right ventricular dimensions, particularly RV end-diastolic volume index (cardiac preload hypothesis).
Empire Prevent Metabolic: (1) To evaluate whether 6 months of treatment with 10 mg of Empagliflozin reduces visceral adipose tissue and improve glucose tolerance in elderly and obese patients with cardiovascular disease (Visceral adiposity and glycemic control hypothesis)
(2) To evaluate whether 6 months of treatment with 10 mg of Empagliflozin increases erythropoietin production and induce changes in iron metabolism in elderly and obese patients with cardiovascular disease (Erythropoietic response hypothesis)
(3) Empagliflozin improves myocardial contractile reserve by an increase in plasma concentrations of ketone bodies. (Ketone bodies hypothesis)
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E.3 | Principal inclusion criteria |
(1)Age 60-84 years (2) Bodymass index >28 kg/m2 (3) Documented cardiovascular disease by any one of following: (3a) Hypertension (3b) Documented ischemic heart disease (3c) Stroke or transitory cerebral ischemia (3d) Chronic kidney disease with GFR 30-45 ml/min/1,72m2 |
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E.4 | Principal exclusion criteria |
(1) Diabetes mellitus (type 1 or 2) (2) Heart failure with ejection fraction <40% (3) Inability to perform exercise test (4) Dementia (5) Non-compliance (6) Substance abuse (7) GFR <30 ml/min/1,72m2 (8) Severe chronic obstructive pulmonary disease (FEV1< 50% expected value) (9) Permanent atrial fibrillation (10) Severe peripheral artery disease (11) Cancer treatment within one year beside prostate cancer and basal cell carcinoma (12) Severe aortic or mitral valve disease (13) Acute hospital admission within 30 days (14) Participation in other pharmacological study (15) Pregnancy (16) Breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
(1) Change from baseline in peak oxygen consumption (VO2) in elderly (2) Change from baseline in left ventricular (LV) mass index (3) Change from baseline in estimated extracellular volume (eECV) (4) Change from baseline in epicardial adipose tissue (EAT) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline in: (1) Daily activity level measured by an accelerometer (2) Self-reported quality of life (3) Cardiac fibrosis (4) Left atrial maximal and minimal volume (5) Ambulatory blood pressure (6) Arterial vascular stiffness (7) Plasma concentrations of ketone bodies (8) Pericardial and paracardial adipose tissue (9) Visceral adipose tissue (10) Glycemic control (11) Estimated plasma volume (12) Secretion of erythropoietin, hepcidin and erythroferrone (13) Changes in ferritin, transferrin saturation and reticulocyte count (14) Serum urate (14) Glomerular filtration rate (15) Right ventricular dimensions (diastolic and systolic)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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
| 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 | 2 |
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 | Yes |
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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End of trial when last visit of the last subject undergoind 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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |