Evaluation of Ticagrelor Versus Acetylsalicylic Acid for Single Antiplatelet Therapy Post-Transcatheter Aortic Valve Implantation in Severe Symptomatic Aortic Stenosis

The primary objective of this study is to assess the **safety** and efficacy of Ticagrelor versus Aspirin in the incidence of Net Adverse Clinical Event (NACE) at 12 months following Transcatheter Aortic Valve Implantation (TAVI). NACE is a composite endpoint that includes all-cause mortality, transient ischemic attack (TIA) or stroke, myocardial infarction, progressive angina leading to emergency evaluation, rehospitalization or new coronary angiography, valve thrombosis, claudication, acute limb ischemia leading to hospitalization, and any bleeding. This evaluation is clinically relevant as it aims to determine the optimal antiplatelet therapy to minimize adverse events in patients with severe symptomatic aortic stenosis undergoing TAVI.

Secondary objectives include:

• Evaluating subclinical valve thrombosis (SVT) through hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RLM) at 3 and 12 months post-TAVI using 4-dimensional computed tomography (4D-CT) imaging.
• Assessing major bleeding events (type 2, 3, and 5) at 12 months post-TAVI according to the Bleeding Academic Research Consortium (BARC) criteria.
• Analyzing patient-oriented composite endpoints (POCE) at 12 months post-TAVI, which include all-cause mortality, TIA/stroke, myocardial infarction, progressive angina leading to emergency evaluation, rehospitalization, or new coronary angiography.
• Investigating individual components of NACE at 12 months post-TAVI.
• Conducting subgroup analyses based on gender, age, valve type, and comorbidities.
• Developing a thrombotic and bleeding risk score for TAVI patients.

The clinical trial focuses on evaluating the safety and efficacy of Ticagrelor versus Aspirin in patients with **Severe Symptomatic Aortic Stenosis**. The study population includes adult patients over the age of 18, encompassing both male and female participants. The trial does not involve a vulnerable population. Participants are required to have undergone a successful Transcatheter Aortic Valve Implantation (TAVI) and must not be involved in any other clinical trials, although participation in registries is permitted. The trial population was selected based on their acceptance for TAVI with any commercially approved TAVI devices, following evaluation by the Heart Team of each center. Additionally, participants must have at least one comorbidity such as Diabetes Mellitus, prior coronary artery disease, or prior peripheral arterial disease. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and efficacy of **ticagrelor** versus **aspirin** in patients with severe symptomatic aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). This is a multicenter, randomized, double-blind, controlled trial. The trial aims to assess the incidence of Net Adverse Clinical Events (NACE) at 12 months post-TAVI, which includes all-cause mortality, transient ischemic attack (TIA) or stroke, myocardial infarction, progressive angina, valve thrombosis, claudication, acute limb ischemia, and any bleeding. The trial commenced on January 21, 2022, and is expected to conclude by July 21, 2024.

Participants will be involved in the study for a maximum of 12 months. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor health status and treatment effects, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be adults with severe symptomatic aortic stenosis, who have undergone successful TAVI and are not involved in other clinical trials. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study if they experience adverse events that compromise their safety, if they withdraw consent, or if they fail to comply with the study protocol. The primary endpoints include all-cause mortality, TIA or stroke, myocardial infarction, and bleeding at 12 months post-TAVI. Secondary endpoints involve major bleeding, subclinical valve thrombosis, and other clinical parameters assessed at 3 and 12 months post-TAVI. The trial is not categorized as low intervention and uses authorized investigational medicinal products.

The clinical trial involves the administration of **Brilique** 60 mg film-coated tablets, which contain the active substance **ticagrelor**. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 120 mg, with a total treatment period of up to 12 months. The administration schedule requires participants to take the medication twice daily, ensuring a consistent therapeutic level of the active substance. Compliance with the dosing regimen is monitored through regular follow-up visits and pill counts to ensure adherence to the prescribed treatment protocol.

In addition to the experimental treatment, the study includes a comparator treatment using **Adiro** 100 mg gastro-resistant tablets, which contain **acetylsalicylic acid** as the active ingredient. This medication is also administered orally, with a maximum daily dose of 100 mg. The treatment duration for the comparator is similarly set at 12 months. Participants are instructed to take the medication once daily, and adherence is monitored through similar compliance checks as with the experimental treatment. The use of a gastro-resistant formulation is intended to minimize gastrointestinal side effects commonly associated with acetylsalicylic acid.

The efficacy of the clinical trial will be assessed by evaluating the incidence of **Net Adverse Clinical Event (NACE)** at 12 months following Transcatheter Aortic Valve Implantation (TAVI). NACE is a composite endpoint that includes several critical outcomes: all-cause mortality, transient ischemic attack (TIA) or stroke, myocardial infarction, progressive angina leading to emergency evaluation, rehospitalization or new coronary angiography, valve thrombosis, claudication, acute limb ischemia leading to hospitalization, and any bleeding. These parameters will be measured at the 12-month mark post-TAVI to determine the efficacy of Ticagrelor versus Aspirin.

Primary endpoints include all-cause mortality, TIA or stroke, myocardial infarction, and bleeding at 12 months post-TAVI, assessed according to the Bleeding Academic Research Consortium (BARC) criteria. Secondary endpoints will involve the incidence of major bleeding (type 2, 3, and 5) at 12 months, subclinical valve thrombosis detected by hypoattenuated leaflet thickening and reduced leaflet motion at 3 and 12 months, and other factors such as gender, age, valve type, comorbidities, and thrombotic and bleeding risk scores. The assessment of subclinical valve thrombosis will be conducted using 4-dimensional computed tomography (4DCT) imaging in pre-specified centers.