Aspirin versus Aspirin plus Clopidogrel in Patients Undergoing Transcatheter Aortic Valve

INTERVENTION: Trade Name: CARDIRENE ‐ 75 MG POLVERE PER SOLUZIONE ORALE 30 BUSTINE Pharmaceutical Form: Powder for oral solution INN or Proposed INN: LISINA ACETILSALICILATO Current Sponsor code: ASA Other descriptive name: acetyl salicilic acid Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 75‐ Trade Name: CLOPIDOGREL DOC GENERICI ‐ 75 MG COMPRESSE RIVESTITE CON FILM 30 COMPRESSE IN BLISTER PVC/PE/PVDC/AL Product Name: clopidogrel Product Code: clopidogrel Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: clopidogrel besilato Current Sponsor code: clopidogrel Other descriptive name: clopiodogrel Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 75‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] valvular aortic stenosis submitted to TAVI ; MedDRA version: 20.0 Level: PT Classification code 10002918 Term: Aortic valve stenosis System Organ Class: 10007541 ‐ Cardiac disorders SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints of the study. In addition to the risk of death, stroke / systemic embolism, rehospitalization due to clinical deterioration due to thrombotic prosthesis dysfunction, other secondary endpoints of the study include:; to. The individual components of the primary endpoint; b. Cardiac death; c. The incidence of TIA and the stroke and TIA composite; d. The composite of death or stroke / systemic embolism; is. The composite of death or rehospitalization due to clinical deterioration due to thrombotic prosthesis dysfunction; f. The composite of death, peripheral stroke / embolism, rehospitalization due to clinical deterioration due to thrombotic prosthesis dysfunction, or type 3 or 5 bleeding according to the BARC definition; g. Thrombotic prosthesis dysfunction in the absence of clinical deterioration; These objectives will also be assessed at 1 year of follow‐up by randomization. Timepoint(s) of evaluation of this end point: 12 months PRIMARY OUTCOME: Main Objective: The primary objective of the study is to determine whether ASA 75 mg / day is superior to ASA 75 mg / day + clopidogrel 75 mg / day for 6 months for the primary endpoint specified below. Primary end point(s): L’endpoint primario dello studio è il composito di morte, stroke/embolismo sistemico, riospedalizzazione per deterioramento clinico dovuto a disfunzione trombotica della protesi, o sanguinamenti tipo 2, 3, 5 secondo la definizione del Bleeding Academic research Consortium (BARC) a 6 mesi dalla randomizzazione. La definizione del sanguinamento secondo i criteri BARC è riportata nella Tabella 1 sottostante insieme con le definizioni degli altri endpoint dello studio secondo il consenso del Valve Academic Research Consortium (VARC). Per deterioramento clinico si intende la presenza di edema o congestione polmonare, scompenso cardiaco congestizio, angina non correlata a coronaropatia, sincope o altri sintomi di bassa portata cardiaca. Per disfunzione trombotica della protesi si intende la presenza di gradiente trans protesico medio > 20 mmHg o di insufficienza della protesi di grado severo dovuta a difetto di un lembo valvolare verosimilmente secondario a trombosi di protesi. La presenza di insufficienza aortica dovuta ad un rigurgito paravalvolare non è da considerare disfunzione di protesi ai fini dell’endpoint primario. Le differenze tra i due gruppi di trattamento riguardo l’endpoint primario saranno analizzate mediante analisi di Kaplan‐Meier e con il log‐rank test, come specificato più in dettaglio nei metodi statistici. Secondary Objective: The secondary objective of the study is the evaluation of non‐inferiority of ASA versus ASA + clopidogrel for risk of death, stroke / systemic embolism, rehospitalization due to clinical deterioration due to thrombotic dysfunction of the prosthesis. Other secondary objectives of the study are the evaluation of other secondary endpoints specified below. Timepoint(s) of evaluation of this end point: 6 months INCLUSION CRITERIA: 1) Patients undergoing an effective and uncomplicated procedure. Effective TAVI intervention means the correct positioning of a single aortic prosthesis in the appropriate anatomic site, with a residual gradient <20 mmHg and in the absence of severe aortic valvular insufficiency. Uncomplicated TAVI intervention means an effective implantation of prostheses in the absence of strokes, major bleeding types 3b, 3c or 5 according to the BARC definition, vascular complications according to the VARC definition (Table 1), coronary obstruction, or acute valvular dysfunction requires a new implant of prosthesis or surgical conversion. 2) Age> 18 years 3) Obtaining informed consent 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 462 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300