Platelet REACtivity According to TICagrelor Dose After Transcatheter AorticValve Implantation

Study Overview
=================
Brief Summary
-----------------
The narrowing of the aortic valve, which prevents blood from reaching the entire body correctly is a common disease in our environment. To correct this problem, many patients undergo Transcatheter Aortic Valve Implantation (TAVI) according to standard clinical practice. Patients have to continue with a specific pharmacological treatment (antiplatelet agents) to avoid possible complications during the first months after the procedure. This treatment is not yet well established. Current guidelines recommend dual antiplatelet therapy with Aspirin and Clopidogrel for 3-6 months after TAVI to avoid thromboembolic complications. But the risk of bleeding events with DAPT in this population is not negligible. This study aims to determine the degree of response to Ticagrelor 60 mg every 12 hours as a single antiplatelet strategy in patients who do not achieve an adequate response with Clopidogrel 75mg every 24 hours. The study will evaluate if patients have an adequate response to Clopidogrel and if not, then patients will start treatment with Ticagrelor 60 mg every 12 hours after TAVI and until completing 3 months of treatment.

Official Title
-----------------
REACTIC-TAVI Trial: Platelet REACtivity According to TICagrelor Dose After Transcatheter AorticValve Implantation. A Pilot Study.

Conditions
-----------------
Symptomatic Aortic Stenosis

Intervention / Treatment
-----------------
* Drug: Ticagrelor 60mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with severe symptomatic aortic stenosis Accepted for transfemoral TAVI by a Heart Team decision Evaluation of platelet reactivity assessed by VerifyNow® assay prior TAVI Exclusion Criteria: Contraindication to TAVI TAVI performed by a different access route than transfemoral Ned for oral anticoagulation therapy History of intracranial hemorrhage Ischemic stroke the 14 days before TAVI Active pathological bleeding or diathesis Moderate to severe hepatic impairment Use of strong CYP34A inhibitors or inducers Contraindications to DAPT for 3 months Contraindication to clopidogrel or ticagrelor Platelet count <50,000 Pregnancy or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Clopidogrel 75 mg<br>Platelet reactivity will be assessed by VerifyNow P2Y12 assay in ALL enrolled patients after confirmed use of clopidogrel for 4 days prior TAVI. Patients that have not completed a pre-treatment period of 4 days of clopidogrel will receive a loading dose of 300mg, according to the clinical practice, with assessment of platelet reactivity by VerifyNow P2Y12 at the following 6 hours. Based on results of basal VerifyNow P2Y12 assay at least 24 hours before the index-TAVI procedure, patients with: Normal basal platelet reactivity (PRU < 160 assessed with VerifyNow P2Y12 assay): Patients will continue with clopidogrel 75 mg/day until TAVI and during the following three months. All patients will be assessed by clinical follow up and platelet reactivity according to the protocol. Prescription of aspirin 100mg/day will be encourage as per guidelines recommendations. | |
| Active Comparator: Ticagrelor 60 mg<br>Platelet reactivity will be assessed by VerifyNow P2Y12 assay in ALL enrolled patients after confirmed use of clopidogrel for 4 days prior TAVI. Patients that have not completed a pre-treatment period of 4 days of clopidogrel will receive a loading dose of 300mg, according to the clinical practice, with assessment of platelet reactivity by VerifyNow P2Y12 at the following 6 hours. Based on results of basal VerifyNow P2Y12 assay at least 24 hrs before the index-TAVI procedure, patients with: High on-treatment platelet reactivity (PRU ≥ 160 assessed with VerifyNow P2Y12 assay): Patients will be switched to receive ticagrelor 60mg twice daily initiating at least 24 hours before TAVI procedure, in order to arrive to the index TAVI procedure with at least two doses of 60 mg, and will continue with Ticagrelor 60mg twice per day during the following three months. | Drug: Ticagrelor 60mg<br>* Platelet reactivity will be assessed by VerifyNow P2Y12 assay in ALL enrolled patients after confirmed use of clopidogrel for 4 days prior TAVI. Patients that have not completed a pre-treatment period of 4 days of clopidogrel will receive a loading dose of 300mg, according to the clinical practice, with assessment of platelet reactivity by VerifyNow P2Y12 at the following 6 hours. Based on results of basal VerifyNow P2Y12 assay at least 24 hours before the index-TAVI procedure, patients with: High on-treatment platelet reactivity (PRU ≥ 160 assessed with VerifyNow P2Y12 assay): Patients will be switched to receive ticagrelor 60mg twice daily initiating at least 24hrs before TAVI procedure, in order to arrive to the index TAVI procedure with at least two doses of 60 mg, and will continue with Ticagrelor 60mg twice per day during the following three months.<br>* Other names: High platelet reactivity patients;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of treatment in suppressing High Platelet Reactivity | Assess the efficacy of ticagrelor 60 mg/12 hours in suppressing High Platelet Reactivity after TAVI. Platelet reactivity will be assessed by VerifyNow P2Y12. | At least 24 hours before the index-TAVI procedure | 
| Efficacy of treatment in suppressing High Platelet Reactivity | Assess the efficacy of ticagrelor 60 mg/12 hours in suppressing High Platelet Reactivity after TAVI. Platelet reactivity will be assessed by VerifyNow P2Y12. | 24 ± 2 hour post TAVI | 
| Efficacy of treatment in suppressing High Platelet Reactivity | Assess the efficacy of ticagrelor 60 mg/12 hours in suppressing High Platelet Reactivity after TAVI. Platelet reactivity will be assessed by VerifyNow P2Y12. | 30 ± 7 days post TAVI | 
| Efficacy of treatment in suppressing High Platelet Reactivity | Assess the efficacy of ticagrelor 60 mg/12 hours in suppressing High Platelet Reactivity after TAVI. Platelet reactivity will be assessed by VerifyNow P2Y12. | 90 ± 7 days post TAVI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Security: incidence of hemorrhagic complications | Evaluate the incidence of hemorrhagic complications after TAVI. As safety endpoint we will assess the incidence of investigator-reported clinical events according to VARC-2 criteria (death, myocardial infarction, stroke, TIA, acute renal injury, bleeding, vascular access-site and access-related complications), including BARC bleeding definitions. For safety endpoint, all BARC criteria, included in VARC-2 criteria will be recorded. | 1) At least 24 hours before the index-TAVI procedure 2) 3) 4) 5) | 
| Security: incidence of hemorrhagic complications | Evaluate the incidence of hemorrhagic complications after TAVI. As safety endpoint we will assess the incidence of investigator-reported clinical events according to VARC-2 criteria (death, myocardial infarction, stroke, TIA, acute renal injury, bleeding, vascular access-site and access-related complications), including BARC bleeding definitions. For safety endpoint, all BARC criteria, included in VARC-2 criteria will be recorded. | 24 ± 2 hour post TAVI | 
| Security: incidence of hemorrhagic complications | Evaluate the incidence of hemorrhagic complications after TAVI. As safety endpoint we will assess the incidence of investigator-reported clinical events according to VARC-2 criteria (death, myocardial infarction, stroke, TIA, acute renal injury, bleeding, vascular access-site and access-related complications), including BARC bleeding definitions. For safety endpoint, all BARC criteria, included in VARC-2 criteria will be recorded. | 30 ± 7 days post TAVI | 
| Security: incidence of hemorrhagic complications | Evaluate the incidence of hemorrhagic complications after TAVI. As safety endpoint we will assess the incidence of investigator-reported clinical events according to VARC-2 criteria (death, myocardial infarction, stroke, TIA, acute renal injury, bleeding, vascular access-site and access-related complications), including BARC bleeding definitions. For safety endpoint, all BARC criteria, included in VARC-2 criteria will be recorded. | 90 ± 7 days post TAVI | 
| Security: incidence of hemorrhagic complications | Evaluate the incidence of hemorrhagic complications after TAVI. As safety endpoint we will assess the incidence of investigator-reported clinical events according to VARC-2 criteria (death, myocardial infarction, stroke, TIA, acute renal injury, bleeding, vascular access-site and access-related complications), including BARC bleeding definitions. For safety endpoint, all BARC criteria, included in VARC-2 criteria will be recorded. | 120 ± 7 days post TAVI | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Transcatheter aortic valve implantation (TAVI), Transcatheter aortic valve replacement (TAVR), Antiplatelet therapy, Ticagrelor, Clopidogrel