E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diabetes mellitus and heart failure |
DIABETE MELLITO ED INSUFFICIENZA CARDIACA CRONICA |
|
E.1.1.1 | Medical condition in easily understood language |
diabetes mellitus and heart failure |
DIABETE MELLITO ED INSUFFICIENZA CARDIACA CRONICA |
|
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 | 10011949 |
E.1.2 | Term | Decompensation cardiac |
E.1.2 | System Organ Class | 100000004849 |
|
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 effect of empagliflozin on LV remodeling and function To assess the effects of empagliflozin on biomarkers of HF hemodynamic status, i.e. natriuretic peptides levels, that are associated to prognosis in HF patients |
Valutazione degli effetti di empagliflozin sul rimodellamento ventricolare sinistro e sulla funzione miocardica Valutazione degli effetti di empagliflozin sui biomarkers di stato emodinamico (peptidi natriuretici) |
|
E.2.2 | Secondary objectives of the trial |
To assess the effects of empagliflozin on myocardial sympathetic nervous system activity trough the assessment of catecholamine behaviors at the synaptic level evaluated by myocardial scintigraphy with I123-metaiodo-benzylguanidine (I123-MIBG) |
Valutazione degli effetti di empagliflozin sull’innervazione miocardica adrenergica attraverso lo studio del comportamento delle catecolamine a livello dello spazio sinaptico mediante scintigrafia con I123-metaiodo-benzilguanidina (I123-MIBG) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age =18 years; • Post-menopausal women, or no-pregnancy state (documented by pregnancy test); • LVEF = 40% in at least two consecutive transthoracic echocardiographic evaluations; • Stable clinical conditions (NYHA class II-III); • Diagnosis of HF since at least 6 months; • Stable optimal pharmacological HF therapy since at least 6 weeks; • Type 2 DM with an indication to treatment with empagliflozin; • Estimated glomerular filtration rate (eGFR) =30 ml/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) criteria; • Capability to understand the study procedures and sign the informed consent form. |
Età = 18 anni • Donne in menopausa o in cui sia certamente escluso lo stato gravidico (attraverso idonei test); • Frazione d’eiezione del ventricolo sinistro =40% in almeno due determinazioni ecocardiografiche consecutive; • Condizioni cliniche stabili (NYHA classe II-III); • Diagnosi di insufficienza cardiaca da almeno 6 mesi; • Trattamento farmacologico stabile da almeno 6 settimane; • Presenza di diabete mellito di tipo 2; • Filtrato glomerulare >30 ml/min/1.73m2 (MDRD formula); • Capacità di comprendere le procedure dello studio e firmare il consenso informato. |
|
E.4 | Principal exclusion criteria |
Age =75 years; • Type 1 DM; • Suspected or known liver disease, defined by serum levels of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal; • Planned cardiac surgery (including heart transplantation) or percutaneous coronary intervention within 3 months; • Acute coronary syndrome, stroke, or transient ischemic attack within 2 months before the inclusion in the study; • Estimated glomerular filtration (eGFR) <30 ml/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) criteria; • Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption; • Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells; • Medical history of cancer and/or treatment for cancer within the last 5 years; |
Età =75 anni; • Diabete mellito di tipo 1; • Malattia epatica nota o sospetta, definite da livelli di transaminasi sieriche e fosfatasi alcalina 3 volte superiori al livello di normalità; • Chirurgia cardiaca o intervento di rivascolarizzazione coronarica percutanea programmato nei successivi 3 mesi; • Sindrome coronarica acuta, stroke, o transient ischemic attack nei 2 mesi precedenti l’inclusione nello studio; • Pazienti con malattie infiammatorie o infettive acute durante i 3 mesi precedenti l’inclusione nello studio; • Pazienti affetti da malattie infiammatorie, immunitarie o infettive croniche; • Pazienti con storia di neoplasie maligne negli ultimi 5 anni; |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To assess the effect of empagliflozin on LV remodeling and function To assess the effects of empagliflozin on biomarkers of HF hemodynamic status, i.e. natriuretic peptides levels, that are associated to prognosis in HF patients |
Valutazione degli effetti di empagliflozin sul rimodellamento ventricolare sinistro e sulla funzione miocardica. Valutazione degli effetti di empagliflozin sui biomarkers di stato emodinamico (peptidi natriuretici) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To assess the effects of empagliflozin on myocardial sympathetic nervous system activity trough the assessment of catecholamine behaviors at the synaptic level evaluated by myocardial scintigraphy with I123-metaiodo-benzylguanidine (I123-MIBG) |
Valutazione degli effetti di empagliflozin sull’innervazione miocardica adrenergica attraverso lo studio del comportamento delle catecolamine a livello dello spazio sinaptico mediante scintigrafia con I123-metaiodo-benzilguanidina (I123-MIBG) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.4 | Safety | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
studio di coorte prospettico |
Prospective cohort study |
|
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.8.4.1 | 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 | Information not present in EudraCT |
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
|
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |