E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes and heart failure |
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E.1.1.1 | Medical condition in easily understood language |
Diabetes and heart failure |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010684 |
E.1.2 | Term | Congestive heart failure |
E.1.2 | System Organ Class | 100000004849 |
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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 | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
The primary objective will be to assess whether empagliflozin (SGLT2 Inhibitor) can augment the effects of loop diuretics in diabetic patients with mild congestive heart failure with left ventricular systolic dysfunction (LVSD), as measured by urinary volume. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the safety of add-on SGLT2 inhibitor therapy in addition to loop diuretics by assessment of change to eGFR and serum creatinine. To assess effects of empagliflozin on protein/creatinine ratio, albumin/creatinine ratio, change to serum cystatin C levels and change to urinary sodium excretion when compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged 18 to 80 years with previously diagnosed Type 2 Diabetes Mellitus. • Are diagnosed with NYHA Functional class II-III HF with prior echocardiographic evidence of LVSD. • On stable doses of furosemide, or alternative loop diuretic for at least one month. • Stable Type 2 Diabetes (HbA1c, in the last 3 months, of 6.5% ≤ and ≤10.0%) • eGFR ≥ 45 ml/min. • Have stable HF symptoms for at least three months prior to consent • On stable HF therapy for at least three months prior to consent • Have not been hospitalised for HF for at least three months prior to consent. • Women of childbearing potential (WoCBP) must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.
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E.4 | Principal exclusion criteria |
• A diagnosis of chronic liver disease and/or liver enzymes that are twice the upper limit of normal • Systolic BP of <95mmHg at screening visit. • Participants on thiazide diuretics. • Participants receiving renal dialysis • Participants who have previously had an episode of diabetic ketoacidosis. • Participants with type 1 diabetes mellitus • Malignancy (receiving active treatment) or other life threatening disease. • Pregnant or lactating women • Participants with difficulty in micturition e.g. severe prostate enlargement • Allergy to any SGLT2 inhibitor or lactose or galactose intolerance • Past or current treatment with any SGLT2 inhibitor • Participants who have participated in any other clinical interventional trial of an investigational medicinal product within 30 days. • Participants who are unable to give informed consent • Any other reason considered by the physician to be inappropriate for inclusion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure for the study will be to measure change in urinary volume with empagliflozin (SGLT2 inhibitor) when compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The effect of empagliflozin when used in conjunction with intravenous furosemide on urinary volume will be evaluated with a renal physiological tests at day 3 and week 6 of each treatment period (empagliflozin and placebo)i.e. visits 3, 5, 7 and 9 at week 1, 6, 9, and 15 respectively.
There will also be four 24 urinary collections made on the day prior to the renal physiological tests, in which a measurement of urinary volume will be collected. |
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E.5.2 | Secondary end point(s) |
Safety of empagliflozin in addition to loop diuretic with measurements of serum creatinine and eGFR when compared to placebo, effects of empagliflozin on protein/creatinine ratio, albumin/creatinine ratio, cystatin C, and on urinary sodium excretion when compared to placebo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
This will be evaluated throughout the trial via blood tests at visits 1, 2 (visits 1 and 2 combined where possible), visit 3, visit 5 and following two week washout period, at visits 6, 7 and 9 for serum cystatin C, eGFR, and serum creatinine.
'Spot' urine tests will be made on these occasions for albumin/creatinine and protein/creatinine ratio. In addition a 24 urinary collection will be made the day prior to the four renal physiology test days (visits 3, 5, 7, and 9) to further assess change to the urinary sodium excretion. |
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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 | No |
E.8.1.6 | Cross over | Yes |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |