E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High cardiovascular risk haemodialized statin intolerant patients with hypercholesterolemia. |
pazienti ad alto rischio cardiovascolare con ipercolesterolemia, intolleranti alle statine ed emodializzati |
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E.1.1.1 | Medical condition in easily understood language |
Haemodialized patients with high cardiovascular risk with sustained cholesterol levels and intolerant to statins. |
Pazienti emodializzati ad alto rischio cardiovascolare con alti livelli di colesterolo e intolleranti alle statine |
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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 | HLGT |
E.1.2 | Classification code | 10013317 |
E.1.2 | Term | Lipid metabolism disorders |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10007541 |
E.1.2 | Term | Cardiac disorders |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10047065 |
E.1.2 | Term | Vascular disorders |
E.1.2 | System Organ Class | 10047065 - Vascular 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 endpoint of this trial is to determine whether the treatment with a new therapeutic strategy (Evolocumab + Ezetimibe) is non-inferior to Ezetimibe alone, in reducing the LDL-C percentage from baseline to week 24, considering an ITT approach, in high cardiovascular risk statin-intolerant patients with hypercholesterolemia and ESRD, receiving maintenance haemodialysis. |
L'obiettivo primario di questo studio è determinare se il trattamento con una nuova strategia terapeutica che prevede l’aggiunta di Evolocumaballa terapia standard a base di Ezetimibe non sia inferiore al solo trattamento standard (Ezetimibe)nel ridurre la percentuale di colesterolo LDL dal basale T0 alla settimana 24 (T24), considerando un approccio ITT, in pazienti con altro rischio cardiovascolare, intolleranti alle statine, con ipercolesterolemia ed insufficienza renale e sottoposti a emodialisi di mantenimento. |
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E.2.2 | Secondary objectives of the trial |
To assess whether the new treatment with Evolocumab+Ezetimibe is non-inferior to usual therapy with Ezetimibe alone in terms of LDL-C reduction, comparing baseline measures versus 4, 12, 24 weeks measures; To evaluate the changes of other lipid parameters (HDL cholesterol, non-HDL cholesterol, triglycerides) from baseline to week 24 (ITT/on-treatment analysis); To evaluate the percentage of patients that reach the LDL-C < 70 mg/dL target at week 24 (ITT/on-treatment analysis); To evaluate the tolerability of Evolocumab, analyzing adverse events reports and laboratory values from the time of signed informed consent until the end of the study, and the hemodynamic stability during haemodialysis. |
Valutare se l’aggiunta di Evolocumabal trattamento standard di Ezetimibe sia non inferiore alla normale terapia con il solo Ezetimibe in termini di riduzione del colesterolo LDL, confrontando le misure di riferimento (baseline – T0) rispetto alle misure prese a 4, 12, 24 settimane. Valutare i cambiamenti di altri parametri lipidici (colesterolo HDL, colesterolo non HDL, trigliceridi) dal basale alla settimana 24; Valutare la percentuale di pazienti che raggiungono l'obiettivo LDL-C<70 mg/dL alla settimana 24. Valutare la tollerabilità di Evolocumab, in aggiunta alla terapia standard, analizzando il profilo di sicurezza tramite l’analisi degli eventi avversi edei valori di laboratorio, nonché della stabilità emodinamica durante l'emodialisi, durante tutta la durata dello studio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be included in the study if all of the following criteria are met: - Age = 18; both genders. - High cardiovascular risk patients defined as: patients with established coronary heart disease (CHD), OR patients with CHD risk equivalents (ischemic stroke, peripheral artery disease, diabetes mellitus plus at least 2 additional risk factors); - Statin-intolerant patients with not adequately controlled LDL-C levels (=70 mg/dL) - Patients with uremia on periodic haemodialysis treatment. |
I pazienti saranno inclusi nello studio se tutti i seguenti criteri sono soddisfatti: - Età = 18; entrambi i sessi. - Pazienti con alto rischio cardiovascolare definiti come: pazienti con malattia coronarica cardiaca accertata (CHD), pazienti con OR con valori di rischio CHD (ictus ischemico, malattia delle arterie periferiche, diabete mellito più almeno 2 fattori di rischio aggiuntivi); - Pazienti intolleranti alle statine con livelli di LDL-C adeguatamente controllati (=70 mg/dL) - Pazienti con uremia su trattamento emodialitico periodico. |
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E.4 | Principal exclusion criteria |
- LDL-C <70 mg/dL - Age < 18 years. |
- LDL-C <70 mg/dL; - Età inferiore ai 18 anni. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Observing in high cardiovascular risk statin-intolerant patients with hypercholesterolemia and ESRD, receiving maintenance haemodialysis, a LDL-C level reduction of at least 20 mg/dL |
L’endpoint primario è rappresentato, nella popolazione in studio, da una riduzione del livello di colesterolo LDLdi almeno 20 mg/dLmisurato mediante ultracentrifugazione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The survey will take place at the 24th week |
La rilevazione avverrà alla 24 settimana |
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E.5.2 | Secondary end point(s) |
- To observe a LDL-C reduction comparing baseline measures versus 4, 12, 24 weeks measures, considering the new treatment with Evolocumab+Ezetimibe versus Ezetimibe alone; - To describe the changes of other lipid parameters (HDL cholesterol, non-HDL cholesterol, triglycerides) from baseline to week 24 (ITT/on-treatment analysis); - To observe the percentage of patients that reach the LDL-C < 70 mg/dL target at week 24 (ITT/on-treatment analysis). - To evaluate the tolerability of Evolocumab, analyzing adverse events reports and laboratory values from the time of signed informed consent until the end of the study, and the hemodynamic stability during haemodialysis. |
- Riduzione del valore di LDL-C, confrontando le misure basali rispetto alle misure a 4, 12, 24 settimane, confrontando il nuovo trattamento con Evolocumab +Ezetimibe rispetto a Ezetimibe+ Placebo; - Cambiamenti su altri parametri lipidici (colesterolo HDL, colesterolo non HDL, trigliceridi) dal basale alla settimana 24 (analisi ITT/OT); - Percentuale di pazienti che raggiungono il target LDL-C<70 mg/dL alla settimana 24 (analisi ITT/OT). - Tollerabilità di Evolocumab, in termini di variazione percentuale e analisi dei tassi di eventi avversi e valori di laboratorio, nonché della stabilità emodinamica durante l'emodialisi, durante tutta la durata dello studio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The surveys will be carried out at 4,12 and 24 weeks |
Le rilevazione verranno effettuate alla 4, 12 e 24 settimana |
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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 | 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 | 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 | 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
|
last visit of the last subject: LVLS |
ultima visita dell'ultimo soggetto: LVLS |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 19 |