Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation

Study Overview
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Brief Summary
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At present, a variety of antithrombotic regimens are prescribed in the early postprocedure period after transcatheter aortic valve implantation (TAVI). Dual antiplatelet therapy (DAPT) using aspirin and a thienopyridine in the initial period after TAVI is the recommended strategy; however, mono antiplatelet therapy using aspirin is suggested not to be inferior. In patients with atrial fibrillation (AF) or another indication for oral anticoagulation (OAC), no recommendations on best treatment regimen currently exist although triple therapy (OAC + DAPT) is best avoided due to increased bleeding risk. We hypothesise that the omission of clopidogrel in the first 3 months after TAVI is safer and not less beneficial than the addition of clopidogrel to aspirin (cohort A) or OAC (cohort B).

Detailed Description
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The trial consists of two cohorts: Cohort A, patients without an indication for OAC prior to TAVI. Cohort B, patients with an indication for OAC prior to TAVI (eg. atrial fibrillation, mechanic mitral valve prosthesis).

Official Title
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Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation

Conditions
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Aortic Valve Disease, Myocardial Infarction, Stroke, Bleeding

Intervention / Treatment
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* Drug: Aspirin + clopidogrel
* Drug: Aspirin monotherapy
* Drug: OAC + clopicogrel
* Drug: OAC monotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort A 1. Patient has provided written informed consent. Cohort B Need for long-term oral anticoagulation; Patient has provided written informed consent. Exclusion Criteria: Cohort A Need for long-term oral anticoagulation; Drug-eluting stent implantation within 3 months prior to TAVI procedure; Bare-metal stent implantation within 1 month prior to TAVI procedure; Allergy or intolerance to aspirin or clopidogrel. Cohort B Drug-eluting stent implantation within 3 months prior to TAVI procedure; Bare-metal stent implantation within 1 month prior to TAVI procedure; Allergy or intolerance to (N)OAC or clopidogrel.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin + Clopicogrel (Cohort A)<br>Cohort A: patients will receive clopidogrel (75mg quaque die (qD), 3 months) on top of low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patient in Cohort A doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI. | Drug: Aspirin + clopidogrel<br> <br> |
| Active Comparator: Aspirin monotherapy (Cohort A)<br>Cohort A: patients will receive low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patients doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure. | Drug: Aspirin monotherapy<br> <br> |
| Active Comparator: OAC + Clopicogrel (Cohort B)<br>Cohort B: patients will receive clopidogrel (75mg qD, 3 months) on top of OAC (according to its indication). The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. aspirin) at least 5 days prior to the TAVI procedure. | Drug: OAC + clopicogrel<br> <br> |
| Active Comparator: OAC monotherapy (Cohort B)<br>Cohort B: patients will receive OAC according to its indication. It is recommended to continue the OAC therapy peri-procedural (International Normalized Ratio aimed at 2.0). It is recommended to omit antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure. | Drug: OAC monotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoint | The primary outcome is a safety endpoint, defined as freedom of all bleeding complications at 1 year after TAVI. The co-primary outcome is the safety endpoint defined as freedom of non-procedure related bleeding complications at 1 year after TAVI. For the classification of bleeding complications the Bleeding Academic Research Consortium Definition for Bleeding (BARC) bleeding classification is primarily used according to the Valve Academic Research Consortium (VARC). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net-clinical benefit endpoint | The secondary outcome is a net-clinical benefit endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, non-procedure related bleeding, stroke, or myocardial infarction at 1 year after TAVI. | 1 year | 
| Efficacy endpoint | The co-secondary outcome is an efficacy endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, ischemic stroke, or myocardial infarction at 1 year after TAVI. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter Aortic Valve Implantation (TAVI), Transcatheter Aortic Valve Replacement (TAVR), Aortic Valve Disease, Aortic Stenosis, Myocardial Infarction, Ischemic stroke, Bleeding, Thrombosis, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Embolism and Thrombosis, Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Antithrombotic treatment, Oral anticoagulation, Warfarin, Platelet Aggregation Inhibitors, Genetic Testing, Cytochrome P450 2C19 (CYP2C19), Prostaglandin-endoperoxide synthase 2(PTGS2)