High bleeding risk (HBR) patients with a recent acute coronary syndrome (ACS ) who have undergone percutaneous coronary intervention (PCI) and are on double antiplatelet therapy (DAPT) MedDRA version: 20.0 Level: PT Classification code 10051592 Term: Acute coronary syndrome System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: brilique
Product Name: Brilique
Product Code: [Ticagrelor]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TICAGRELOR
CAS Number: 274693-27-5
Current Sponsor code: ticagrelor
Sponsors
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Informed Consent signed and dated. - Patients deemed at HBR according to standard definitions (i.e. PRECISE-DAPT =25 or HBR-ARC with at least 1 major or 2 minor criteria) (Table 1). - Treated with PCI due to a recent ACS (i.e. unstable angina, non-ST segment elevated myocardial infarction or ST segment elevated myocardial infarction) 30 ±7 days earlier. - Treated with DAPT with full-dose potent P2Y12 inhibitors (e.g. prasugrel 10mg or ticagrelor 90mg bid) according to international guidelines recommendations Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
Exclusion criteria: • Known intolerance, hypersensitivity or contraindication (including active bleeding) to aspirin, clopidogrel, prasugrel or ticagrelor • Indication to oral anticoagulation • Indication to prolonged treatment with full-dose potent P2Y12 inhibitors (e.g. previous stent thrombosis, stenting of last remaining vessel, stent with indication for longer-term DAPT, perceived very high coronary ischemic risk etc.) • Any planned major surgery or interventional procedure requiring treatment modification • Prior transient ischemic attack, ischemic or haemorrhagic stroke • Severe hepatic insufficiency (Child-Pugh class C) • Ongoing therapy with strong CYP3A inducers or strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir etc.) • Women who are pregnant or breast feeding or with potential to become pregnant during the course of the study (age < 55 years and last menstruation within the last 12 months) without a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the pharmacodynamic effect of 3 different regimens of P2Y12 inhibitor de-escalation (prasugrel 5mg, ticagrelor 60mg/bid or clopidogrel 75mg) versus full-dose potent P2Y12 inhibitor (prasugrel 10mg or ticagrelor 90mg bid) on platelet reactivity, and to evaluate which treatment achieves the highest proportion of patients in the optimal platelet reactivity (OPR) at treatment steady-state.;Secondary Objective: The key secondary objective is to evaluate the clinical impact of P2Y12 inhibitor de-escalation versus full-dose potent P2Y12 inhibition on major, minor and nuisance bleeding according to the bleeding academic research consortium definition (BARC 1-5 bleeding) at 5 months after randomization. Other secondary objectives will be to evaluate ischemic and net clinical events and quality of life in the four treatment arms. Platelet reactivity at 1 and 2 weeks after P2Y12 inhibitor discontinuation will be evaluated at the end of the study, or anytime during the study, in patients permanently discontinuing treatment;Primary end point(s): The primary endpoint of the study is the incidence of optimal platelet reactivity (OPR) measured by means of the VerifyNow system (Accumetrics, San Diego, CA, USA), 2 hours after drug MD at 14±2 days from study inclusion. OPR will be defined as a PRU between 85 and 208 reactivity units according to international expert consensus.;Timepoint(s) of evaluation of this end point: 14 +/- 2 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoint of the study is the incidence of nuisance, minor or major bleeding according to the BARC definition (BARC 1-5).; Platelet reactive units (PRU) at VerifyNow system and Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS) before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration and before MD at 14±2 days from study inclusion; The proportion of high platelet reactivity (HPR) defined as PRU > 208, and the proportion of low platelet reactivity (LPR), defined as PRU < 85, measured through the VerifyNow system before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days from study inclusion.; Adverse clinical events, assessed at each visit and up to 5 months after randomization. They include: death, cardiac death, non-fatal myocardial infarction, non-fatal stroke, urgent target vessel revascularization, definite/probable stent thrombosis and net adverse clinical events.;Timepoint(s) of evaluation of this end point: 5 months; 14 +/- 2 days; 14 +/- 2 days; up to 5 months after the randomization | — |
Countries
Italy
Contacts
Public ContactClinical Operations
Mediolanum Cardio Resarch Srl
Outcome results
None listed