E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ischaemic stroke |
Ictus Ischemico |
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E.1.1.1 | Medical condition in easily understood language |
Brain damage caused by deprivation of blood. |
Danni cerebrali causati dalla privazione di sangue.
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
E.1.2 | System Organ Class | 100000004852 |
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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 objective of the study is to compare the effect of 90-day treatment with ticagrelor (180 mg [two 90 mg tablets] loading dose on Day 1 followed by 90 mg twice daily maintenance dose for the remainder of the study) vs. acetylsalicylic acid (ASA)-aspirin (300 mg [three 100 mg tablets] loading dose on Day 1 followed by 100 mg once daily maintenance dose for the remainder of the study) for the prevention of major vascular events (composite of stroke, myocardial infarction [MI], and death) in patients with acute ischaemic stroke or transient ischaemic attack (TIA). |
L’obiettivo primario dello studio è comparare l’effetto del trattamento della durata di 90 giorni con ticagrelor (dose di carico al giorno 1: 180 mg in due compresse da 90 mg; seguito dal trattamento di mantenimento per la rimanente durata dello studio: 90 mg in compresse assunte 2 volte al giorno) verso acido acetilsalicilico (ASA) – aspirina TM1 (dose di carico al giorno 1: 300 mg in tre compresse da 100 mg; seguito dal trattamento di mantenimento per la rimanente durata dello studio: compresse da 100 mg assunte 1 volta al giorno) per la prevenzione di eventi vascolari maggiori (insieme di ictus, infarto del miocardio MI e morte) in pazienti con ictus ischemico acuto o attacco ischemico transitorio (TIA). |
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E.2.2 | Secondary objectives of the trial |
Compare the effects of treatment with ticagrelor vs. ASA
on:
1) prevention of subsequent ischaemic stroke.
2) net clinical outcome (stroke + MI + death + life threatening bleeding).
3) prevention of composite of ischaemic stroke, MI and cardiovascular [CV] death.
4) prevention of all-cause death, CV death and MI, individually
5) severity of stroke and overall disability of patients using modified Rankin Scale
6) prevention of all stroke (including haemorrhagic stroke), fatal stroke and disabling stroke, individually.
7) health care resource and utilities assessed by Euro Quality of Life-5 Dimensions to support health technology assessment and health economic modelling. |
comparare gli effetti del trattamento con ticagrelor verso ASA nella:
- prevenzione di eventi di ictus ischemici successivi.
-Risultato clinico netto (ictus + infarto del miocardio + morte + sanguinamento con pericolo di morte)
-Prevenzione dell’evento composito ictus ischemico, infarto del miocardio e morte per cause cardiovascolari (CV)
-Prevenzione di tutte le cause di morte, morte per cause cardiovascolari e infarto del miocardio, singolarmente
-Severità dell’ictus e disabilità complessiva dei pazienti secondo la scala di Rankin
-Prevenzione di tutti gli ictus (incluso quello emorragico), ictus fatali e invalidanti, singolarmente
-Grado di peggioramento, per esempio progressione dell’evento indice di ictus valutato con il deterioramento dei sintomi clinici e/o incremento nel punteggio secondo la scala NIHSS (National Institute of Health Stroke)
-Utilizzo delle risorse sanitarie e delle utenze valutato con EQ5D quest. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men or women equal or elder 40 years of age - Either acute ischaemic stroke not eligible for thrombolysis or mechanical thrombectomy or high-risk TIA as defined here and randomisation occurring within 24 hours after onset of symptoms |
Maschi e femmine di età ≥ 40 anni con ictus ischemico in fase acuta non eleggibile a trombolisi o trombectomia meccanica o TIA ad alto rischio e che siano randomizzati entro 24 ore dall’insorgenza dei sintomi |
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E.4 | Principal exclusion criteria |
Planned use of antithrombotic therapy in addition to study medication including antiplatelets (eg, open label ASA, GPIIb/IIIa inhibitors, clopidogrel, ticlopidine, prasugrel, dipyridamole, ozagrel, cilostazol) and anticoagulants (eg, warfarin, oral thrombin and factor Xa
inhibitors, bivalirudin, hirudin, argatroban, unfractionated and low molecular weight heparins). - Any history of atrial fibrillation, ventricular aneurysm or suspicion of cardioembolic pathology for TIA or
stroke. - Planned carotid, cerebrovascular, or coronary revascularisation that requires halting study medication within 7 days of randomisation. - Receipt of any intravenous or intra-arterial thrombolysis
or mechanical thrombectomy within 24 hours prior to randomisation - History of previous symptomatic non-traumatic intracerebral bleed at any time (asymptomatic microbleeds do not qualify), gastrointestinal (GI) bleed within the past 6 months, or major surgery within 30 days. |
1. Uso pianificato di una terapia antitrombotica in aggiunta al farmaco dello studio compresi gli antipiastrinici (es. ASA in aperto, inibitori GPIIb/IIIa, clopidogrel, ticlopidina, prasugrel, dipiridamolo, ozagrel, cilostazolo) e anticoagulanti (es. warfarina, inibitori orali della trombina e fattore Xa, bivalirudina, irudina, argatroban, eparina non frazionata e a basso peso molecolare). Ipersensibilità nota a ticagrelor o ASA e qualunque paziente per cui il trattamento con aspirina è controindicato.
2. Qualunque episodio/storia di precedente fibrillazione atriale, aneurisma ventricolare o sospetta patologia cardioembolica per TIA o stroke
3. Rivascolarizzazione programmata coronarica, cerebrovascolare o carotidea che richiede la sospensione del farmaco dello studio entro 7 giorni dalla randomizzazione
4. Assunzione nelle 24 ore precedenti la randomizzazione di qualunque trombolitico intra-venoso o intra-arterioso o trombectomia meccanica
5. Qualunque episodio/storia di precedente sanguinamento sintomatico intracerebrale non traumatico (i micro-sanguinamenti non vengono considerati), sanguinamento gastrointestinale (GI) nei 6 mesi precedenti, o operazione chirurgica nei 30 giorni precedenti l’inizio dello studio.
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E.5 End points |
E.5.1 | Primary end point(s) |
Composite of stroke, MI and death. |
evento composito di stroke, infarto miocardico e morte |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization for 2.5 year (min.treatment duration) |
Dalla randomizzazione per 2,5 anni (durata min.trattamento)
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E.5.2 | Secondary end point(s) |
Composite of ischaemic stroke, MI and CV death.
Net clinical outcome.
Time to discontinuation of study medication due to any bleeding event. |
evento compositodi ictus ischemico, infarto miocardico e morte cardiovascolare.
Risultato clinico netto.
Tempo di sospensione del farmaco in studio a causa di qualsiasi evento di sanguinamento.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomization for 2.5 year (min.treatment duration) |
Dalla randomizzazione per 2,5 anni (durata min.trattamento)
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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 | No |
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 | Yes |
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 | 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 | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 165 |
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 |
Bulgaria |
Canada |
China |
France |
Italy |
Japan |
Romania |
Slovakia |
Sweden |
Argentina |
Australia |
Brazil |
Chile |
Czech Republic |
Germany |
Hong Kong |
Korea, Republic of |
Spain |
Thailand |
Mexico |
Peru |
Philippines |
Poland |
Russian Federation |
Switzerland |
Taiwan |
Turkey |
Ukraine |
United States |
Vietnam |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |