E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pre-heart failure with preserved ejection fraction |
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E.1.1.1 | Medical condition in easily understood language |
Heart failure means the heart is not able to pump or relax effectively. Heart failure with preserved ejection fraction means that the changes in the heart is related to an impairment in relaxation. |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076396 |
E.1.2 | Term | Heart failure with preserved ejection fraction |
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 assess the impact of Empagliflozin on diastolic dysfunction measured by LAVImax over 6 months in non-diabetic pre-HFPEF patients using CMR. |
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E.2.2 | Secondary objectives of the trial |
● To assess the effect of Empagliflozin versus usual medical care on CMR left ventricular structure and function ● To assess the effect of Empagliflozin on Brain Natriuretic Peptide and eGFR
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged >40 years old with at least one cardiovascular risk factor(s) including: a. Hypertension b. Coronary artery disease c. Obesity d. Previous ischaemic stroke or TIA e. Peripheral vascular disease f. Hypercholesterolaemia g. Previous chemotherapy or radiotherapy to the chest
2) Not currently on SGLT-2i treatment 3) LAVI ≥29mL/m2 obtained by Doppler echocardiography 4) Are able and agree to Fitbit use and exercise prescription 5) Subjects must be able and willing to give written informed consent 6) Access to a smart phone 7) Non-diabetic
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E.4 | Principal exclusion criteria |
1. Aged >85years old 2. Subjects with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption 3. Recent (within 3 months) acute myocardial infarction or stroke 4. Permanent or persistent Atrial Fibrillation 5. Any diabetes mellitus 6. Contraindication to SGLT-2i 7. Renal insufficiency with eGFR <20mL per min per 1.73m2. For those patients randomised to the substudy CMR with gadolinium, the eGFR cut off will be <30mL per min per 1.73m2. 8. A history of HF 9. Asymptomatic left ventricular systolic dysfunction as defined as LVEF <50% on most recent measurement. 10. Presence of haemodynamically significant mitral and /or aortic valve disease 11. Conditions that are expected to compromise survival over the study period 12. Concomitant participation in other interventional clinical trials 13. Subjects with contraindications to MRI or allergic reactions to MRI contrast dye (Dotarem) 14. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drugs. 15. Women who are pregnant, breast-feeding, or women of childbearing potential not using estro-progestative oral or intra-uterine contraception or implants, or women using estro-progestative oral or intra-uterine contraception or implants but who consider stopping it during the planned duration of the study. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. (Contraception must be continued for one week following discontinuation of study drug). 16. Refusal to provide informed consent 17. Unable to exercise due to concomitant medical condition, such as severe arthritis, uncontrolled pain, severe airways disease or falls risk. 18. Cognitive impairment 19. Systolic blood pressure <100mmHg
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in LAVI measured by CMR over 6 months |
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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 in CMR LVMI between baseline and 6 months • Change in CMR LVESVi between baseline and 6 months • Change in CMR LVEDVi between baseline and 6 months • Change in CMR LVEF between baseline and 6 months. • Change in CMR e’ between baseline and 6 months. • Change in CMR LV myocardial strain (measured using feature tracking) between baseline and 6 months. • Change in CMR parameter LA myocardial strain (measured using feature tracking) between baseline and 6 months. • Change in serum BNP and eGFR from baseline to 6 months
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 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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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 | |
E.8.9.1 | In the Member State concerned days | |