Evaluation of Personalized CT-Guided Antithrombotic Therapy Versus Standard Single Antiplatelet Therapy in Aortic Valve Stenosis Post-TAVI Patients

The primary objective of this study is to evaluate whether a personalized, **CT-guided antithrombotic strategy** is superior to standard care lifelong single antiplatelet therapy (SAPT) in reducing the risk of cardiovascular mortality, thromboembolic, and bleeding events after transcatheter aortic valve implantation (TAVI) in patients without an existing indication for oral anticoagulation (OAC). This is clinically relevant as it aims to optimize post-TAVI management, potentially improving patient outcomes by minimizing adverse events associated with aortic valve stenosis.

Secondary objectives include evaluating the effect of a CT-guided antithrombotic strategy on:

• Net clinical benefit, defined as the composite of cardiovascular mortality, stroke, transient ischemic attack, systemic embolism, clinically significant valve thrombosis, and type 1-4 bleeding according to the VARC-3 criteria.
• Major bleeding (VARC-3 type 2-4).
• Cerebrovascular events (all stroke and transient ischemic attack according to VARC-3).
• Cardiovascular mortality.
• All-cause mortality.
• Quality of life as assessed by EuroQol-5 Dimension 5 Level (EQ-5D-5L), Kansas City Cardiomyopathy Questionnaire (KCCQ), and Short Form Health Survey (SF-12) at baseline, 3 and 12 months, and then yearly after the TAVI procedure.
• Medication adherence as assessed by the Medication Adherence Report Scale (MARS-5) yearly after randomization.
• Cost-effectiveness of a CT-guided antithrombotic strategy after TAVI.

The clinical trial involves participants diagnosed with **aortic valve stenosis**. The study population includes both male and female subjects, with an age range corresponding to category code 4, which typically represents older adults. The participants are generally in a stable health condition, having undergone a successful Transcatheter Aortic Valve Implantation (TAVI) as per the VARC-3 criteria. The trial does not include a vulnerable population. The selection of participants was based on their ability to understand and comply with the study protocol, and all participants provided written informed consent. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of a personalized, CT-guided **antithrombotic** strategy compared to standard care lifelong single antiplatelet therapy (SAPT) in reducing cardiovascular mortality, thromboembolic, and bleeding events in patients with **aortic valve stenosis** who have undergone transcatheter aortic valve implantation (TAVI). This is a pragmatic, international, multicenter, randomized clinical trial. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is from September 2023 to September 2027, with participant involvement expected to last up to 99 months, depending on the treatment group assignment.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as successful TAVI according to VARC-3 criteria, ability to comply with the study protocol, and provision of written informed consent. Follow-up visits will be scheduled at baseline, 3 months, 12 months, and then annually post-TAVI to monitor primary and secondary endpoints, including thromboembolic and bleeding events, cardiovascular mortality, and quality of life assessments using tools like the EuroQol-5 Dimension 5 Level (EQ-5D-5L) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any necessary follow-up care is arranged.

Participants may be withdrawn from the study early if they experience adverse events that compromise their safety, are unable to comply with the study protocol, or withdraw consent. The trial's primary endpoints focus on thromboembolic and bleeding events, while secondary endpoints include net clinical benefit, major bleeding, cerebrovascular events, cardiovascular and all-cause mortality, and aortic bio-prosthetic valve dysfunction. The trial also aims to assess the cost-effectiveness of the CT-guided antithrombotic strategy. The investigational medicinal products used in the trial are evidence-based, supported by published scientific evidence on safety and efficacy, and administered orally in various pharmaceutical forms, including tablets and film-coated tablets.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. **KARDEGIC 75 mg** is an oral solution in the form of a powder for solution in sachet-dose, containing **d,l-lysine acetylsalicylate** as the active substance. The maximum daily dose is 75 mg, administered orally, with a treatment period extending up to 9999 days. This product is manufactured by Sanofi Winthrop Industrie.

**Acenocoumarol Sandoz 1 mg** is a tablet containing **acenocoumarol** as the active ingredient. The maximum daily dose is 10 mg, administered orally, with a treatment period of up to 99 days. This product is provided by Sandoz B.V.

**Clopidogrel Xiromed 75 mg** is a film-coated tablet containing **clopidogrel**. The maximum daily dose is 300 mg, administered orally, with a treatment period of up to 99 days. This product is manufactured by Medical Valley Invest AB.

**MINI-SINTROM 1 mg** is a tablet containing **acenocoumarol**. The maximum daily dose is 99 mg, administered orally, with a treatment period extending up to 9999 days. This product is provided by Merus Labs Luxco II S.à r.l.

**Eliquis 5 mg** and **Eliquis 2.5 mg** are film-coated tablets containing **apixaban**. Both have a maximum daily dose of 10 mg, administered orally, with a treatment period of up to 99 days. These products are manufactured by Bristol-Myers Squibb/Pfizer EEIG.

**Prasugrel Teva 10 mg** is a film-coated tablet containing **prasugrel**. The maximum daily dose is 60 mg, administered orally, with a treatment period of up to 99 days. This product is provided by Teva UK Limited.

**Ticagrelor Mylan 90 mg** is a film-coated tablet containing **ticagrelor**. The maximum daily dose is 180 mg, administered orally, with a treatment period of up to 99 days. This product is manufactured by McDermott Laboratories Ltd.

**Warfarin Teva 2.5 mg** and **COUMADINE 2 mg** are tablets containing **warfarin sodium**. Warfarin Teva has a maximum daily dose of 25 mg, while COUMADINE has a maximum daily dose of 99 mg, both administered orally. Warfarin Teva is provided by Sun Pharmaceutical Industries Europe B.V., and COUMADINE is manufactured by Teofarma S.R.L.

**Acetylsalicylzuur Cardio Mylan 80 mg** is a dispersible tablet containing **acetylsalicylic acid**. The maximum daily dose is 80 mg, administered orally, with a treatment period of up to 99 days. This product is provided by Mylan B.V.

**Fenprocoumon Sandoz 3 mg** is a tablet containing **phenprocoumon**. The maximum daily dose is 30 mg, administered orally, with a treatment period of up to 99 days. This product is manufactured by Sandoz B.V.

All medications are administered orally, and participant compliance is monitored throughout the trial. The trial aims to evaluate the efficacy of a personalized, CT-guided antithrombotic strategy compared to standard care in reducing cardiovascular mortality, thromboembolic, and bleeding events in patients post-transcatheter aortic valve implantation.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints focus on **thromboembolic** and bleeding events, defined as a composite of cardiovascular mortality, ischemic stroke, transient ischemic attack, myocardial infarction, systemic embolism, and clinically significant valve thrombosis, as well as all bleeding events categorized from type 1 to 4 according to the VARC-3 criteria. Secondary endpoints include net clinical benefit, major bleeding (VARC-3 type 2-4), cerebrovascular events, cardiovascular mortality, all-cause mortality, and aortic bio-prosthetic valve dysfunction assessed by echocardiography yearly after TAVI. Quality of life will be evaluated using the EuroQol-5 Dimension 5 Level (EQ-5D-5L), Kansas City Cardiomyopathy Questionnaire (KCCQ), and Short Form Health Survey (SF-12) at baseline, 3 and 12 months, and then yearly post-TAVI. Medication adherence will be assessed using the Medication Adherence Report Scale (MARS-5) yearly after randomization. The cost-effectiveness of a CT-guided antithrombotic strategy post-TAVI will also be evaluated.