Platelet Reactivity After TAVI: A Multicenter Pilot Study

Study Overview
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Brief Summary
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A high platelet reactivity in patients with severe symptomatic Aortic Stenosis (AS) selected for TAVI (Transcatheter aortic valve implantation) procedure has been demonstrated previously, and the use of double antiaggregation therapy (DAPT) with Clopidogrel and Acetylsalicylic acid (ASA) do not achieve consistent and adequate suppression of platelet reactivity. The purpose of this study is evaluate the efficacy of ticagrelor alone versus DAPT with clopidogrel and aspirin for the suppression of high platelet reactivity following TAVI.

Official Title
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Assessment of Platelet REACtivity After Transcatheter Aortic Valve Implantation

Conditions
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Severe Aortic Valve Stenosis, Transcatheter Aortic Valve Implantation, Transcatheter Aortic Valve Replacement

Intervention / Treatment
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* Drug: Ticagrelor 90 mg twice per day during three months following TAVI
* Drug: Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study subjects should fulfill the following criteria: Provision of informed consent prior to any study specific procedures. Adult patients (more than 18 years) with ability to understand and accept the participation in the clinical trial. Patients with degenerative symptomatic severe AS accepted for TAVI after evaluation of the Heart Team of each center. Patients who are not participating in any other clinical trial or research study (registries allowed). Exclusion Criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: Recent stroke <14 days prior to TAVI, non-revascularized severe coronary or carotid artery disease (>70% stenosis) or life expectancy < 12 months Patients under chronic oral anticoagulation Patients with proven allergy to aspirin, clopidogrel or ticagrelor Patients that after TAVI cannot undergo a regimen of single or dual antiplatelet therapy for 3 months due to a new post-TAVI medical indication Known pregnancy or breast-feeding Concomitant oral or intravenous therapy with potent inhibitors of cytochrome P450 3A (CYP3A) that cannot be suspended during the course of the study. Medications considered as potent inhibitors are: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (or erythromycin but not astromicin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and more than a daily liter of grapefruit juice. Thrombocytopenia (<50,000 platelets U/L) well documented and clinically relevant. Patients with documented moderate or severe hepatic insufficiency Any condition that may put the patient at risk or influence the outcome of the trial Patients previously randomized in this trial or in another clinical trial with an investigational product or device over the past 30 days. Patients who cannot attend follow up visits scheduled in the study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>Patients with high-on-treatment platelet reactivity (PRU ≥ 208) | Drug: Ticagrelor 90 mg twice per day during three months following TAVI<br> <br> |
| Active Comparator: Aspirin/Clopidogrel<br>Patients with high-on-treatment platelet reactivity (PRU ≥ 208) | Drug: Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI<br> <br> |
| No Intervention: Registry arm<br>Patients with normal-on-treatment platelet reactivity (PRU < 208) will continue with Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by a system to verify the patient's platelet reactivity (VerifyNow P2Y12 assay). |  | Three months after antiplatelet treatment initiation following procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by VerifyNow P2Y12 assay. |  | Six hours after antiplatelet treatment initiation following procedure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic stenosis, TAVI, TAVR, Transcatheter aortic valve implantation, Ticagrelor, Antiplatelet reactivity