E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dyslipidemia |
Dislipidemia |
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E.1.1.1 | Medical condition in easily understood language |
Abnormal amounts of lipids in the blood |
Quantità anormali di lipidi nel sangue |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058110 |
E.1.2 | Term | Dyslipidemia |
E.1.2 | System Organ Class | 100000004861 |
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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 evaluate the effect of treatment with evolocumab, compared with placebo, on the risk for coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke, whichever occurs first, in subjects at high cardiovascular risk without prior MI or stroke and receiving optimized lipid-lowering therapy. -To evaluate the effect of treatment with evolocumab, compared with placebo, on the risk for CHD death, MI, ischemic stroke, or any ischemiadriven arterial revascularization, whichever occurs first, in subjects at high cardiovascular risk without prior MI or stroke and receiving optimized lipid-lowering therapy. |
- Valutare l’effetto del trattamento con evolocumab, rispetto al placebo, sul rischio di IM, ictus ischemico o rivascolarizzazione arteriosa causata da ischemia in soggetti ad alto rischio cardiovascolare senza anamnesi pregressa di IM o ictus trattati con terapia ipolipemizzante ottimizzata - Valutare l’effetto del trattamento con evolocumab, rispetto al placebo, sul rischio di morte per CHD, di IM o rivascolarizzazione arteriosa causata da ischemia in soggetti ad alto rischio cardiovascolare senza anamnesi pregressa di IM o ictus trattati con terapia ipolipemizzante ottimizzata |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of treatment with evolocumab, compared with placebo, on the risk for: 1. MI, ischemic stroke, or any ischemia driven arterial revascularization; 2. CHD death, MI, or any ischemia-driven arterial revascularization; 3. cardiovascular death, MI, or stroke; 4. MI; 5. any ischemia-driven arterial revascularization; 6. CHD death; 7. cardiovascular death; 8. all cause of death; 9. ischemic stroke; in subjects at high cardiovascular risk without prior MI or stroke and receiving optimized lipid-lowering therapy. |
- Valutare gli effetti del trattamento con evolocumab, rispetto al placebo, sui rischi di: 1. IM, ictus ischemico o rivascolarizzazione arteriosa causata da ischemia 2. morte per CHD, IM, o rivascolarizzazione arteriosa causata da ischemia 3. morte cardiovascolare, IM o infarto 4. IM 5. rivascolarizzazione arteriosa causata da ischemia 6. morte per CHD 7. morte cardiovascolare 8. tutte le cause di morte 9. ictus ischemico in soggetti ad alto rischio cardiovascolare senza anamnesi pregressa di IM o ictus trattati con terapia ipolipemizzante ottimizzata |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Subject has provided informed consent prior to initiation of any study specific activities/procedures -Adult subjects > = 50 years (men) or > = 55 years (women) to < 80 years of age (either sex) and meeting lipid criteria -Subjects must have an LDL-C > = 90 mg/dL (> = 2.3 mmol/L) or non-HDLC > = 120 mg/dL (> = 3.1 mmol/L) OR apolipoprotein B >= 80 mg/dL (>= 1.56 µmol/L) 1. Lipid entry criteria can be measured up to 3 months prior to screening in the absence of changes to background therapy 2. Lipid criteria should be assessed after >= 2 weeks of stable, optimized lipid-lowering therapy 3. The most recent results (historical or screening) must be used -Diagnostic evidence of at least 1 of the following (A – D) at screening: A. Significant coronary artery disease meeting at least 1 of the following criteria: 1. History of coronary revascularization with multi-vessel coronary disease as evidenced by any of the following: (a) percutaneous coronary intervention (PCI) of 2 or more vessels, including branch arteries (b) PCI or coronary artery bypass grafting (CABG) with residual > =50% stenosis in a separate, unrevascularized segment or vessel, or (c) multi-vessel CABG 5 years or more prior to screening 2. Significant coronary disease without prior revascularization as evidenced by either a > = 70% stenosis of at least 1 coronary artery, > = 50% stenosis of 2 or more coronary arteries, or > = 50% stenosis of the left main coronary artery 3. known coronary artery calcium score > = 100 in subjects without a coronary artery revascularization prior to randomization B. Significant atherosclerotic cerebrovascular disease meeting at least 1 of the following criteria: 1. prior transient ischemic attack with > = 50% carotid stenosis 2. internal or external carotid artery stenosis of > = 70% or 2 or more > = 50% stenosis 3. prior internal or external carotid artery revascularization C. Significant peripheral arterial disease meeting at least 1 of the following criteria: 1. > = 50% stenosis in a limb artery 2. history of abdominal aorta treatment (percutaneous and surgical) due to atherosclerotic disease 3. ankle brachial index (ABI) < 0.85
*Please refer to protocol for the full list |
- Il soggetto ha fornito il consenso informato prima di iniziare qualsiasi attività / procedura specifica dello studio - I soggetti devono essere di età > = 50 anni (per gli uomini) o > = 55 anni (per le donne) e < 80 anni (per entrambi i sessi) e soddisfare i criteri lipidici - I soggetti devono avere un C-LDL > = 90 mg/dL (= 2,3 mmol/L) o colesterolo legato alle lipoproteine non ad alta densità (C-non HDL) > = 120 mg/dL (= 3,1 mmol/L) o apolipoproteina B >= 80mg/dL (>=1,56 µmol/L) 1. I criteri lipidici iniziali possono essere misurati fino a 3 mesi prima dello screening in assenza di modifiche alla terapia di base 2. I criteri lipidici dovrebbero essere valutati dopo >= 2 settimane di terapia stabile e ottimizzata per l'abbassamento dei lipidi 3. Devono essere utilizzati i risultati più recenti (anamnestici o screening) - Evidenza diagnostica di almeno una delle seguenti (A - D) allo screening: A. Coronaropatia significativa che rispetti almeno uno dei seguenti criteri: 1. Anamnesi di rivascolarizzazione coronarica con malattia coronarica multivasale come evidenziato da uno dei seguenti elementi: - (a) intervento coronarico percutaneo (PCI) di 2 o più vasi, incluse le arterie secondarie - (b) PCI o innesto di bypass aortocoronarico (CABG) con stenosi residua > = 50% in un segmento o vaso separato non rivascolarizzato, o - (c) CABG multivasale 5 anni o più prima dello screening 2. Malattia coronarica significativa senza anamnesi pregressa di rivascolarizzazione come evidenziato da una stenosi > = 70% di almeno un’arteria coronaria, > = 50% stenosi di 2 o più arterie coronarie o stenosi > = 50% dell'arteria coronaria principale sinistra 3. Punteggio relativo al calcio coronarico noto > = 100 in soggetti senza rivascolarizzazione dell'arteria coronarica prima della randomizzazione B. Cerebrovasculopatia aterosclerotica significativa che rispetti almeno uno dei seguenti criteri: 1. pregressa anamnesi di attacco ischemico transitorio con stenosi carotidea > = 50% 2. stenosi carotidea interna o esterna pari a = 70% o 2 o più stenosi > = 50% 3. pregressa anamnesi di rivascolarizzazione dell’arteria carotidea interna o esterna C. Arteropatia periferica significativa che rispetti almeno 1 dei seguenti criteri: 1. stenosi > = 50% in un’arteria degli arti 2. anamnesi di trattamento dell’aorta addominale (percutaneo e chirurgico) causato da malattia aterosclerotica 3. indice caviglia-brachiale (ABI) < 0,85
*Fare riferimento al protocollo per la lista completa |
|
E.4 | Principal exclusion criteria |
1. Disease Related - MI or stroke prior to randomization - CABG < 3 months prior to screening - Uncontrolled or recurrent ventricular tachycardia in the absence of an implantable-cardioverter defibrillator. - Atrial fibrillation or atrial flutter not on anticoagulation therapy (vitamin K antagonist, heparin, low-molecular weight heparin, fondaparinux, or non-Vitamin K antagonist oral anticoagulant) - Last measured left-ventricular ejection fraction < 30% or New York Heart Association (NYHA) Functional Class III/IV - Planned arterial revascularization 2. Diagnostic Assessments - Triglycerides > =500 mg/dL (5.7 mmol/L) measured up to 3 months prior to screening. The most recent results must be used. - End stage renal disease (ESRD), defined as an eGFR < 15 mL/min/1.73 m2 or receiving dialysis measured up to 6 months prior to screening. The most recent results must be used.
*Please refer to the protocol for the full list |
1. Correlati alla patologia - MI o infarto prima della randomizzazione - CABG < 3 mesi prima dello screening - Tachicardia ventricolare non controllata o ricorrente in assenza di defibrillatore cardiaco impiantabile - Fibrillazione atriale o flutter atriale non in terapia anticoagulante (antagonisti della vitamina K, eparina, eparina a basso peeso molecolare, fondaparina o anticoagulanti orali non antagonisti della vitamina K) - Ultima frazione di eiezione ventricolare sinistra misurata < 30% o classe funzionale III/IV della New York Heart Association (NYHA) - Rivascolarizzazione atriale pianificata 2. Valutazione diagnostica - Trigliceridi > = 500 mg/dL (5,7 mmol/L) misurati fino a 3 mesi prima dello screening. Devono essere utilizzati i risultati più recenti. - Malattia renale allo stadio terminale (ESRD), definita come eGFR < 15mL/min/1.73 m2 o sotto dialisi rilevata fino a 6 mesi prima dello screening. Devono essere utilizzati i risultati più recenti.
*Fare riferimento al protocollo per la lista completa |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Time to CHD death, MI, or ischemic stroke, whichever occurs first - Time to CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurs first |
- Tempo alla morte per CHD, IM o ictus, a seconda di quale evento si verifichi per primo - Tempo alla morte per CHD, IM, ictus ischemico o rivascolarizzazione arteriosa causata da ischemia, a seconda di quale evento si verifichi per primo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continually during treatment period and at EOS |
Costantemente durante lo studio clinico ed alla sua conclusione |
|
E.5.2 | Secondary end point(s) |
- Time to MI, ischemic stroke, or any ischemia-driven arterial revascularization - Time to CHD death, MI, or any ischemia-driven arterial revascularization - Time to cardiovascular death, MI, or stroke - Time to MI - Time to any ischemia-driven arterial revascularization - Time to CHD death - Time to cardiovascular death - Time to all cause of death - Time to ischemic stroke |
- Tempo all’IM, ictus ischemico o rivascolarizzazione arteriosa causata da ischemia - Tempo alla morte per CHD, IM o rivascolarizzazione arteriosa causata da ischemia - Tempo alla morte cardiovascolare, IM o ictus - Tempo all’IM - Tempo alla rivascolarizzazione arteriosa causata da ischemia - Tempo alla morte per CHD - Tempo alla morte cardiovascolare - Tempo alla morte per qualsiasi causa - Tempo all’ictus ischemico |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continually during treatment period and at EOS |
Costantemente durante lo studio clinico ed alla sua conclusione |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
studio degli outcomes cardiovascolari |
cardiovascular outcomes study |
|
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 350 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
China |
Korea, Democratic People's Republic of |
Russian Federation |
Taiwan |
United States |
Bulgaria |
Denmark |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
United Kingdom |
Czechia |
Argentina |
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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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LVLS |
Ultima visita dell'ultimo paziente |
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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 | 5 |
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 | 5 |
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 |