E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute coronary syndrome |
Sindrome coronarica acuta |
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E.1.1.1 | Medical condition in easily understood language |
Acute coronary syndrome |
Sindrome coronarica acuta |
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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 | PT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
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 |
The main aim of the trial is to determine whether the efficacy of ticagrelor 60 mg twice daily is not inferior to that of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI. |
L’obiettivo principale dello studio è determinare se l’efficacia di Ticagrelor 60mg due volte al giorno è non inferiore a quella di Ticagrelor 90 mg due volte al giorno in pazienti anziani con SCA sottoposti ad angioplastica coronarica percutanea. |
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E.2.2 | Secondary objectives of the trial |
To evaluate adverse events in patients treated with ticagrelor 60 mg and ticagrelor 90 mg. To determine the pharmacokinetic profile of ticagrelor 60 mg twice daily versus ticagrelor 90 mg twice daily. |
Valutare gli eventi avversi nei pazienti trattati con ticagrelor 60 mg e ticagrelor 90 mg. Determinare il profilo farmacocinetico di Ticagrelor 60 mg due volte al giorno rispetto a Ticagrelor 90 mg due volte al giorno. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to provide written informed consent in a time window 1 to 3 days after successful PCI; 2. Male or female, age = 75 years at screening; ¿ 3. ACS at the time of the index hospitalization; 4. Use of a loading dose of 180 mg of ticagrelor administered after diagnosis of ACS or after PCI; 5. Use of a maintenance dose of 90 mg twice daily of ticagrelor of at least 48 hours after the loading dose; 6. Successful PCI (Thrombolysis In Myocardial Infarction [TIMI] flow 3 and residual coronary stenosis <30%) for non-ST-segment elevation ACS or ST-segment elevation myocardial infarction |
1. Capacità di fornire il consenso informato scritto in una finestra di tempo tra 1 e 3 giorni dopo la PCI efficace 2. Uomini e donne di età = 75 anni al momento dello screening; 3. SCA al momento del ricovero; 4. Somministrazione di una dose di carico di 180 mg di ticagrelor ; 5. Somministrazione di una dose di mantenimento di ticagrelor 90 mg due volte al giorno per almeno 48 ore dopo la dose di carico; 6. PCI efficace (flusso coronarico anterogrado TIMI 3 e stenosi coronarica redisua < 30%) per infarto miocardico con o senza sopraslivellamento del segmento ST |
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E.4 | Principal exclusion criteria |
1. Use of glycoprotein IIb/IIIa receptor inhibitors; 2. Need for chronic oral anticoagulant therapy; 3. Prior fibrinolysis; 4. Unstable clinical status (hemodynamic or electrical instability); 5. Planned surgery requiring DAPT discontinuation during the study; 6. Prior stroke, transient ischemic attack or intracranial bleeding; 7. Active bleeding; 8. Severe anemia (hemoglobin < 8g/dL); 9. Platelet count =80x103/ml; 10. Renal failure (hemodialysis or creatinine clearance = 30 ml/min calculated with Cockroft- Gault formula); 11. Severe hepatic dysfunction (baseline alanine aminotransferase = 2.5 times the upper limit of normal); 12. Known hypersensitivity or contraindication to ticagrelor; 13. Inhability to sign informed consent; 14. Under judicial protection, tutorship or curatorship; 15. Unable to understand and follow study-related instructions; 16. Enrollment in another investigational device or drug study. |
1. Somministrazione di inibitori del recettore Gp IIb/IIIa; 2. Indicazione a terapia anticoagulante a lungo termine; 3. Recente fibrinolisi; 4. Condizioni cliniche instabili (instabilità emodinamica o elettrica); 5. Interventi programmati di chirurgia che richiedono una sospensione della DAPT durante lo studio; 6. Precedente ictus, attacco ischemico transitorio, sanguinamento intracranico; 7. Sanguinamento attivo; 8. Anemia severa (emoglobina <8 g/dL); 9. Conta piastrinica = 80 x 103/ml; 10. Insufficienza renale (emodialisi o clearance della creatinina = 30 ml/min calcolata con formula di Cockroft- Gault); 11. Severa disfunzione epatica (livelli di transaminasi = 2.5 volte il limite superiore di normalità); 12. Ipersensibilità o controindicazioni all’utilizzo del ticagrelor; 13. Inabilità a firmare il consenso informato; 14. Soggetto sotto tutela giuridica; 15. Incapacità a comprendere e seguire le procedure previste dallo studio; 16. Arruolamento in altri studi clinici. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the trial will be the comparison of pre-dose P2Y12 reaction units (PRU) determined by VerifyNow- P2Y12 assay (Accumetrics, San Diego, California) at 14 days after treatment with ticagrelor 60 mg or 90 mg. |
L’endpoint primario sarà confrontare il PRU (Unità di Reazione P2Y12) tra i due gruppi di trattamento, determinato mediante il VerifyNow-P2Y12 (Accumetrics, San Diego, California), 14 giorni dopo trattamento con ticagrelor 60 mg o 90 mg. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline and 14 and 28 days after treatment with ticagrelor 60 mg or 90 mg. |
al basale, 14 e 28 giorni dopo il trattamento con ticagrelor 60 mg o 90 mg |
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E.5.2 | Secondary end point(s) |
High platelet reactivity (HPR) and ADP-induced platelet reactivity measured through light transmittance aggregometry (LTA) and Multiplate Analyzer.; Non ADP-induced platelet reactivity in patients treated with ticagrelor 60 mg or ticagrelor 90 mg, measured through Multiplate Analyzer (arachidonic acid-, collagen-, and thrombin receptor-activating test).; Frequency of any revascularization; Frequency of Unstable angina; Frequency of Bleeding events according to the BARC, TIMI and GUSTO classification.; Plasma levels of ticagrelor and its active metabolite AR-C124910XX.; Frequency of Spontaneous myocardial infarction;; The composite of all-cause death, myocardial infarction, or stroke; The composite of cardiovascular death, myocardial infarction, urgent target-lesion revascularization; |
Studio dell’aggregazione piastrinica indotta dall’ADP e determinazione di elevata reattività piastrinica (HPR) attraverso l’utilizzo l’Aggregometria a Luce Trasmessa (LTA) e il Multiplate.; Reattività piastrinica non indotta da ADP in pazienti trattati con ticagrelor 60 mg o ticagrelor 90 mg, misurata mediante Multiplate Analyzer (test di attivazione del recettore dell'acido arachidonico, del collagene e della trombina).; Frequenza di ogni rivascolarizzazione; Frequenza di angina instabile;; Frequenza degli eventi di sanguinamento in accordo con le classificazioni BARC,TIMI e GUSTO;; Livelli di Ticagrelor nel plasma e il suo metabolita attivo AR-C124910XX.; Frequenza di infarto miocardico spontaneo;; Composito di morte per tutte le cause, infarto miocardico o ictus;; Composito di morte cardiovascolare, infarto miocardico, rivascolarizzazione urgente della lesione target |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 time points: 1) Time 1: at baseline before randomization; 2) Time 2: 14 days after the first randomly assigned treatment, including 2 samples, before and 2 hours after the last dose of the initial assigned treatment; 3) Time: 14 days after the second randomly assigned treatment, including 2 samples, before and 2 hours after the last dose of the second assigned treatment; 3 time points: 1) Time 1: at baseline before randomization; 2) Time 2: 14 days after the first randomly assigned treatment, including 2 samples, before and 2 hours after the last dose of the initial assigned treatment; 3) Time: 14 days after the second randomly assigned treatment, including 2 samples, before and 2 hours af |
3 time points: 1) Time 1: baseline, prima della randomizzazione; 2) Time 2: 14 giorni dopo l’inizio del primo trattamento assegnato , includendo 2 campioni, prima e 2 ore dopo l'ultima dose del primo trattamento assegnato; 3) Time 3: 14 giorni dopo l’inizio del secondo trattamento assegnato, includendo 2 campioni, prima e 2 ore dopo l'ultima dose del secondo trattamento assegnato; 3 time points: 1) Time 1: baseline, prima della randomizzazione; 2) Time 2: 14 giorni dopo l’inizio del primo trattamento assegnato , includendo 2 campioni, prima e 2 ore dopo l'ultima dose del primo trattamento assegnato; 3) Time 3: 14 giorni dopo l’inizio del secondo trattamento assegnato, includendo 2 campioni, prima e 2 ore dopo l'ultima dose del secondo trattamento assegnato; durante |
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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 | Yes |
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 | Yes |
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
| 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |