E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) diagnosed at least 3 months prior to informed consent. |
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E.1.1.1 | Medical condition in easily understood language |
Heart failure is when the heart cannot not keep up enough blood flow to the rest of the body because of a weak or stiff pumping chamber of the heart. |
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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 | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 |
To investigate the mechanism by which empagliflozin improves heart failure related outcomes (health) in patients with heart failure. |
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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. Chronic heart failure diagnosed at least 3 months before informed consent 2. NYHA class II-IV at screening
HFrEF: LVEF < 40% as measured by echocardiogram (ECHO) at screening and; - Elevated NT-proBNP (>125 pg/mL) in patient without atrial fibrillation (AF) or NT-proBNP (>600 pg/mL) in patient with AF at screening
HFpEF: LVEF ≥ 50% as measured by ECHO at screening and; - Structural heart disease as shown by left atrial enlargement and/or left ventricular hypertrophy by ECHO at screening - NT-proBNP > 125pg/mL in patient without AF or NT-proBNP > 600 pg/mL in patient with AF at screening |
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E.4 | Principal exclusion criteria |
1. Stroke or transient ischaemic attack (TIA) within 6 months prior to informed consent. 2. Any patients with myocardial scars and/or non-viable myocardium in the interventricular septum, unstable angina due to significant coronary artery disease (CAD), or major (in the opinion of the investigator) cardiovascular surgery. 3. Any contraindication for MRI, CPET and/or dobutamine stress test in accordance with the institution guidance 4. Cardiomyopathies such as due to amyloidosis, haemochromatosis, Fabry disease, muscular dystrophies, stress cardiomyopathy, hypertrophic obstructive cardiomyopathy 5. Moderate to severe valvular heart disease 6. Acute decompensated HF (exacerbation of chronic HF) requiring intravenous treatment or hospitalisation within 1 week prior to Visit 1 (Screening), or during screening period until Visit 2 (Randomisation) 8. Uncontrolled hypertension 9. Symptomatic hypotension and/or a SBP < 100 mmHg at Screening 10. Patients with requirement for treatment with empagliflozin or any SGLT-2 inhibitor according to local standard care 11. Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors 12. Women who are pregnant, breastfeeding, or who plan to become pregnant while in the trial 13. Impaired renal function, defined as estimated Creatinine Clearance < 30 mL/min (using Cockcroft-Gault formula) or requiring dialysis, as determined at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to week 12 in Phosphocreatine/Adenosine Triphospate (PCr/ATP) ratio in resting state measured by 31P Magnetic Resonance Spectroscopy (MRS). |
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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) |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 28 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 12 |