E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of major cardiovascular events in patients with coronary or peripheral artery disease |
Prevenzione di eventi cardiovascolari maggiori in pazienti con malattie arteriose coronariche o periferiche |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of heart attacks, strokes and death in patients with (atherosclerotic) narrowing of the arteries of the heart or legs |
Prevenzione di eventi cardiovascolari maggiori in pazienti con malattie arteriose coronariche o periferiche |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064939 |
E.1.2 | Term | Cardiovascular event prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Primary objectives for rivaroxaban randomization:
•To determine whether rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg once daily (od) compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke, or cardiovascular death in subjects with CAD or PAD
•To determine whether rivaroxaban 5 mg bid compared with aspirin 100 mg od reduces the risk of a composite of myocardial infarction, stroke or cardiovascular death in subjects with CAD or PAD
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• Determinare se il rivaroxaban alla dose di 2,5 mg 2 volte al giorno + aspirina 100 mg 1 volta al giorno, rispetto alla sola aspirina 100 mg 1 volta al giorno , è in grado di ridurre il rischio di infarto miocardico (IM), ictus ischemico o morte cardiovascolare (CV) in pazienti affetti da arteriopatia coronarica (AC) o arteriopatia periferica (AP). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives for rivaroxaban randomization:
•To determine whether each of rivaroxaban 2.5 mg bid + aspirin 100 mg od and rivaroxaban 5 mg bid alone reduces the risk of the composite of major thrombotic events (coronary heart disease death, myocardial infarction, ischemic stroke, acute limb ischemia; cardiovascular death, myocardial infarction, ischemic stroke, acute limb ischemia) compared with aspirin 100 mg od in subjects with CAD or PAD
•To determine whether each of rivaroxaban 2.5 mg bid + aspirin 100 mg od and rivaroxaban 5 mg bid alone reduces the risk of mortality in subjects with CAD or PAD
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Determinare se rivaroxaban alla dose di 2,5 mg 2 volte al giorno + aspirina 100 mg 1 volta al giorno e rivaroxaban dose di 5 mg 2 volte al giorno da solo, riduce il rischio di maggiori eventi trombotici (1) morte per malattia coronarica , infarto miocardico, ictus ischemico , ischemia acuta dell'arto ( 2 ) morte cardiovascolare , infarto miocardico , ictus ischemico, ischemia acuta dell’arto in confronto all’aspirina 100 mg 1 volta al giorno nei pazienti con AC o AP • Determinare se rivaroxaban alla dose di 2,5 mg 2 volte al giorno + aspirina 100 mg 1 volta al giorno e rivaroxaban 5 mg 2 volte al giorno riduce il rischio di mortalità in pazienti con AC o AP
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: The COMPASS MIND substudy is included in section 14 of the COMPASS protocol Objective: Magnetic resonance imaging (MRI) substudy evaluating the incidence of clinically silent brain infarcts and subclinical brain ischemia. Italy will not participate in this substudy
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: : COMPASS MIND Questo sottostudio è descritto nella sezione 14 del protocollo principale. Si tratta di un sottostudio di MRI che ha l’obiettivo di valutare l’incidenza di infarti cerebrali clinicamente silenti e ischemia cerebrale subclinica. L’Italia non parteciperà al sottostudio.
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E.3 | Principal inclusion criteria |
-- Coronary or peripheral artery disease
Patients with coronary artery disease must also meet at least one of the following:
-- Age =65, or
-- Age <65 and documented atherosclerosis or revascularization involving at least 2 vascular beds, or at least 2 additional risk factors |
I pazienti sono eleggibili per l’inclusione se:
hanno i criteri per AC * e/o per AP
I pazienti con AC devono anche avere almeno 1 dei seguenti criteri:
o età = 65 anni;
o età <65 anni con aterosclerosi documentata o rivascolarizzazione almeno in due letti vascolari o almeno 2 fattori di rischio cardiovascolare addizionali :
o fumatore (entro 1 anno dalla randomizzazione);
o diabete mellito;
o disfunzione renale con eGFR <60 ml/min;
o scompenso cardiaco;
o pregresso ictus ischemico non lacunare ( =1 mese prima).
* Poiché AC coinvolge la malattia del sistema vascolare coronarico, solo un ulteriore letto vascolare è richiesto: es. l’aorta e il flusso arterioso al cervello, tratto gastro-intestinale, gli arti inferiori e superiori o i reni
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E.4 | Principal exclusion criteria |
-Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy or oral anticoagulant therapy
-Stroke within 1 month or any history of hemorrhagic or lacunar stroke
-Severe heart failure with known ejection fraction <30% or New York Heart Association (NYHA) class III or IV symptoms
-Estimated glomerular filtration rate (eGFR) <15 mL/min |
• rischio elevato di emorragie;
• ictus entro 1 mese o qualsiasi tipo di ictus emorragico o lacunare pregresso;
• insufficienza cardiaca grave con frazione di eiezione <30% diagnosticata o sintomi di classe III o IV secondo la New York Heart Association (NYHA);
• eGFR<15 ml/min (insufficienza renale grave);
• necessità di terapia di doppia antiaagregazione, altra terapia antipiastrinica senza aspirina o terapia anticoagulante orale;
• malattia non cardiovascolare nota, associata a prognosi infausta (per es. neoplasia metastatica) o che aumenta il rischio di reazione avversa agli interventi dello studio;
• ipersensibilità all'anamnesi o controindicazione nota per rivaroxaban, aspirina, pantoprazolo o loro eccipienti;
• trattamento sistemico con potenti inibitori di entrambe CYP 3A4 e della glicoproteina P (P-gp), per es. antimicotici azolici sistemici quali il chetoconazolo e inibitori della HIV-proteasi quali il ritonavir; o potenti induttori di CYP 3A4, es. rifampicina, rifabutina, fenobarbitolo, fenitoina e carbamazepina
• qualsiasi malattia epatica associata a coagulopatia;
• donne incinte, che allattano o sono potenzialmente fertili e sessualmente attive e non adottano alcun metodo di controllo delle nascite (per es. sterilizzate chirurgicamente, contraccettivi orali su prescrizione, iniezioni contraccettive, dispositivi contraccettivi intrauterini, metodo di barriera doppio, cerotto contraccettivo, sterilizzazione del partner maschile) prima e durante l'intera durata dello studio; donne in età fertile che hanno un test di gravidanza positivo allo screening;
• precedente assegnazione al trattamento durante lo studio.
• partecipazione simultanea ad un altro studio con farmaco sperimentale
• nota controindicazione a qualche procedura dello studio
Un criterio di esclusione aggiuntivo per la randomizzazione per il pantoprazolo è:
• necessità di trattamento continuo con un inibitore della pompa protonica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy end point: Time from randomization to the first occurrence of either myocardial infarction, stroke, or cardiovascular death
Safety end point: Time from randomization to the first occurrence of major bleeding (modified International Society on Thrombosis and Haemostasis) |
1. Combinazione di IM, ictus ischemico e morte CV.
Endpoint primario di sicurezza
Combinazione di emorragia fatale e /o
Emorragia sintomatica in un’area critica o organo, come intracranio, intraspinale, intraoculare, retroperitoneale, intraarticolare o pericardiale, o intramuscolare con compartment syndrome, o emorragia nel sito operato richiedendo un reintervento, e / o Emorragia che richiede un’ospedalizzazione
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 5 years |
circa 5 anni |
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E.5.2 | Secondary end point(s) |
Time from randomization to first occurrence of either Coronary heart disease death, myocardial infarction, ischemic stroke, acute limb ischemia
Time from randomization to first occurrence of either Cardiovascular death, myocardial infarction, ischemic stroke, acute limb ischemia
Time from randomization to first occurrence of all cause mortality |
¿ 1. IM, ictus ischemico, morte coronarica o Ischemia periferica acuta
¿ 2. IM, ictus ischemico, morte CV o Ischemia periferica acuta
¿ 3. Mortalità totale |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 5 years |
circa 5 anni |
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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 | 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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To make rivaroxaban 2.5 mg twice daily twice daily + aspirin 100 mg once daily available to COMPASS trial subjects until the rivaroxaban treatment is commercially available for this indication or for approximately 3 years from regulatory approval of the long term open label extension in a country, whichever comes first. |
To make rivaroxaban 2.5 mg twice daily twice daily + aspirin 100 mg once daily available to COMPASS trial subjects until the rivaroxaban treatment is commercially available for this indication or for approximately 3 years from regulatory approval of the long term open label extension in a country, whichever comes first. |
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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 |
3x2 partial factorial |
3x2 partial factorial |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 215 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
China |
Colombia |
Czechia |
Denmark |
Ecuador |
Finland |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
Philippines |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Sweden |
Switzerland |
Ukraine |
United Kingdom |
United States |
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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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For each participating European Union (EU) country, the end of the study according to the EU Clinical Trial Directive will be reached when the telephone call at the end of the 30 day washout period for the last subject for all centers in the respective country has occurred. The end of the study as a whole will be reached as soon as the end of the study according to the above definition has been reached in all participating countries (EU and non-EU). |
For each participating European Union (EU) country, the end of the study according to the EU Clinical Trial Directive will be reached when the telephone call at the end of the 30 day washout period for the last subject for all centers in the respective country has occurred. The end of the study as a whole will be reached as soon as the end of the study according to the above definition has been reached in all participating countries (EU and non-EU). |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |