E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects either male or female eligible for percutaneous coronary intervention (PCI) with lesions suitable for stent implantation who meet all eligibility criteria and provide written informed consent will be included. Of note, inclusion criteria will be kept comprehensive to reflect routine clinical practice (i.e. “real world, all-comers” patients). |
Soggetti maschi o femmine idonei per una procedura di intervento coronarico percutaneo (PCI) con lesioni adatte ad impianto di stent che soddisfino tutti i criteri di eleggibilità e che hanno firmato un consenso informato. Per nota, i criteri di inclusione saranno mantenuti comprensivi al fine di riflettere la pratica clinica di routine (“Real world”, pazienti “all comers”) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with different levels of chest pain, due to poor blood flow to the heart. To improve the blood flow and symptoms, the artery is reopened followed by applicable treatment by medicines. |
Pazienti con diversi livelli di dolori toracico, dovuti a flusso di sangue scarso al cuore. Per migliorare il flusso del sangue ed sintomi,l’arteria sarà riaperta seguita da un trattamento con farmaci |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011078 |
E.1.2 | Term | Coronary artery disease |
E.1.2 | System Organ Class | 10007541 - Cardiac 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 |
To determine in all-comers patients undergoing PCI under standardised treatment (including the BioMatrix family of drug-eluting stents and bivalirudin), whether treatment with 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy is superior with respect to the composite of all-cause mortality or non-fatal new Q-wave MI compared to treatment with 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. |
Determinare in tutti i pazienti partecipanti che devono essere sottoposti a intervento coronarico percutaneo sotto trattamento standardizzato (comprendente gli stent a rilascio farmacologico della famiglia BioMatrix e bivalirudina), se il trattamento con 1 mese di ticagrelor e aspirina seguito da 23 mesi di monoterapia con ticagrelor è superiore per quanto riguarda il composito di mortalità per tutte le cause o nuovo infarto miocardico non fatale con onda Q rispetto al trattamento con 12 mesi di terapia antipiastrinica standard doppia (DAPT) seguita da monoterapia con aspirina. |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Non applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
“Real world, all comer” patients
1. Age ≥18 years;
2. Presence of one or more coronary artery stenoses of 50% or more in a native coronary artery or in a saphenous venous or arterial bypass conduit suitable for coronary stent implantation in a vessel with a reference vessel diameter of at least 2.25 mm (no limitation on the number of treated lesions, and vessels, and lesion length).
3. Able to provide informed consent and willing to participate in 2 year follow-up period.
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Mondo reale, pazienti "all comers"
1. Età ≥ 18 anni;
2. Presenza di una o più stenosi coronariche al 50% o oltre in un'arteria coronarica nativa o in un condotto di bypass da vena safena o arterioso idoneo all'impianto di uno stent coronarico. Il vaso deve avere un diametro di riferimento di almeno 2,25 mm (nessuna limitazione al numero di lesioni trattate, vasi o lunghezza delle lesioni);
3. In grado di fornire il consenso informato e intenzionati a partecipare al periodo di follow-up di 2 anni.
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E.4 | Principal exclusion criteria |
1. Known intolerance to aspirin, P2Y12 inhibitors, bivalirudin, stainless steel or biolimus;
2. Known intake of a strong CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir), as co-administration may lead to a substantial increase in exposure to ticagrelor;
3. Known moderate to severe hepatic impairment (alanine-aminotransferase ≥ 3 x ULN);
4. Planned surgery, including CABG as a staged procedure (hybrid) within 12 months of the index procedure, unless dual antiplatelet therapy is maintained throughout the peri-surgical period;
5. Need for chronic oral anti-coagulation therapy;
6. Active major bleeding or major surgery within the last 30 days;
7. Known history of intracranial haemorrhagic stroke or intra-cranial aneurysm;
8. Known stroke (any type) within the last 30 days;
9. Known pregnancy at time of randomisation;
10. Currently participating in another trial and not yet at its primary endpoint. |
1. Intolleranza nota all'aspirina, agli inibitori del recettore P2Y12, alla bivalirudina, all'acciaio inossidabile o biolimus;
2. L'assunzione nota di un potente inibitore del CYP3A4 (ad es., ketoconazolo, claritromicina, nefazodone, ritonavir e atazanavir) in somministrazione congiunta può provocare un sostanziale aumento dell'esposizione al ticagrelor;
3. Insufficienza epatica nota moderata o grave (alanina-aminotransferasi ≥ 3 x LSN);
4. Intervento pianificato, tra cui innesto di bypass aortocoronarico (CABG) come intervento programmato (ibrido) entro 12 mesi dalla procedura di valutazione, a meno che la terapia antipiastrinica doppia sia mantenuta per tutto il periodo perichirurgico;
5. Necessità di terapia di anticoagulazione orale cronica;
6. Vasta emorragia attiva o intervento importante entro gli ultimi 30 giorni;
7. Anamnesi nota di ictus emorragico intracranico o aneurisma intracranico;
8. Ictus noto (qualsiasi tipo) entro gli ultimi 30 giorni;
9. Gravidanza nota al momento della randomizzazione;
10. Partecipazione concomitante a un altro studio non ancora all'endpoint primario.
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E.5 End points |
E.5.1 | Primary end point(s) |
The composite of overall mortality or non-fatal new Q-wave MI up to 2 years post-randomization. |
Il composito di mortalità per tutte le cause o nuovo infarto miocardico non fatale con onda Q fino a 2 anni dopo la randomizzazione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 years post-randomization.
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2 anni dalla randomizzazione |
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E.5.2 | Secondary end point(s) |
The composite of BARC3 or BARC5 bleeding according to BARC definitions up to 2 years post-randomization. |
Il composito di emorragia BARC3 o BARC5 riportata dallo sperimentatore in base alle definizioni BARC fino a 2 anni dopo la randomizzazione |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 years post-randomization. |
2 anni dalla randomizzazione |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 | No |
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 |
Austria |
Belgium |
Brazil |
Canada |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
Singapore |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |