Evaluation of Short-Term Versus Long-Term Acetylsalicylic Acid Therapy Post-Transfemoral Transcatheter Aortic Valve Implantation in Symptomatic Aortic Stenosis Patients

The primary objective of this study is to evaluate the **non-inferiority** of a short-term antiplatelet therapy regimen (3 months of 75 to 100 mg oral aspirin) compared to a standard long-term regimen (12 months of 75 to 100 mg oral aspirin) in patients who have undergone successful transfemoral trans-aortic valve implantation (TAVI) for symptomatic aortic stenosis. This is assessed based on a composite clinical event at 12 months follow-up. The clinical relevance of this objective lies in potentially reducing the duration of antiplatelet therapy without compromising patient outcomes, which could minimize the risk of bleeding and improve patient adherence.

Secondary objectives include: - Assessing the superiority of the experimental arm in reducing all bleeding events. - Evaluating the superiority of the experimental arm in reducing clinically significant, major, or disabling bleeding. - Determining the non-inferiority of the experimental arm concerning the composite of major cardiovascular events. - Comparing individual components of composite endpoints and other secondary outcomes between the two arms. - Assessing mortality at 2 years follow-up using the national mortality database.

The clinical trial involves **adult patients** who have undergone successful transfemoral trans-aortic valve implantation (TAVI) for symptomatic **aortic stenosis**. The study population includes both male and female participants, with females being either post-menopausal or permanently sterilized. Participants are aged 18 years and older. The trial does not include a vulnerable population. The selection criteria require participants to have no other indication for long-term antiplatelet or anticoagulant therapy. Participants must be French-speaking and affiliated with social security. The sponsor has not provided the total number of participants involved in the trial. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **non-inferiority** of a short-term antiplatelet therapy regimen compared to a standard long-term regimen in patients who have undergone successful transfemoral trans-aortic valve implantation (TAVI) for symptomatic aortic stenosis. The trial employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. Participants will be randomly assigned to either the experimental arm, receiving 75 to 100 mg of oral aspirin for 3 months, or the standard arm, receiving the same dosage for 12 months. The primary endpoint is the net clinical benefit, defined by a composite of all-cause death, type 1 myocardial infarction, and various types of central nervous system injury and bleeding events, assessed at 12 months post-TAVI.

The trial is expected to commence on January 15, 2024, with an estimated completion date of January 15, 2027. Participants will be involved in the study for a maximum of 12 months, with the possibility of early termination if they experience any adverse events that meet the criteria for withdrawal or if they fail to adhere to the study protocol. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as age, successful TAVI, and informed consent. Follow-up visits will be scheduled at regular intervals to monitor the participants' health status and adherence to the treatment regimen. The end-of-study visit will occur at the 12-month mark, where the primary and secondary endpoints will be evaluated.

Inclusion criteria require participants to be adults aged 18 or older, with successful TAVI as defined by the VARC-3 criteria, and without any other indication for long-term antiplatelet or anticoagulant therapy. Exclusion criteria are not explicitly detailed in the provided data. The trial will be conducted in compliance with ethical standards, and participants will be required to provide written informed consent. The study aims to provide valuable insights into the optimal duration of antiplatelet therapy following TAVI, potentially influencing future clinical guidelines and patient management strategies.

The clinical trial involves the administration of **KARDEGIC 75 mg**, a **poudre pour solution buvable en sachet-dose**. The active substance in this experimental medication is **D,L-lysine acetylsalicylate**, a chemical compound. The pharmaceutical form is an **oral solution**, and it is administered via **oral use**. The dosage is set at 75 mg per sachet, with a maximum daily dose of 100 mg. The treatment period is limited to a maximum of 3 months. The medication is manufactured by Sanofi Winthrop Industrie and is authorized for use in France. Participant compliance with the dosing schedule will be monitored throughout the trial.

The comparator treatment in the study is **ASPIRINE PROTECT 100 mg**, a **comprimé gastro-résistant**. The active substance is **acetylsalicylic acid**, also a chemical compound. This medication is provided in the form of a **gastro-resistant tablet** and is also administered via **oral use**. The dosage is 100 mg per tablet, with a maximum daily dose of 100 mg, and the treatment period is similarly capped at 3 months. This medication is produced by Bayer Healthcare and is likewise authorized for use in France. Compliance with the administration schedule will be closely monitored to ensure adherence to the trial protocol.

Efficacy in the clinical trial titled "Short versus long antiplatelet therapy after TAVI" will be assessed using a primary endpoint and several secondary endpoints. The primary endpoint is defined as the net clinical benefit, which is a composite of all-cause death, type 1 myocardial infarction, NeuroARC types 1a, 1aH, 1b, 1c, 1d ischemic or hemorrhagic central nervous system (CNS) injury, and non-procedure-related major or disabling bleeding as per VARC types 2 or 3, evaluated 12 months after successful transcatheter aortic valve implantation (TAVI).

Secondary endpoints include various measures such as any non-procedure-related bleeding defined by the VARC classification 1 to 4, major or disabling or life-threatening bleeding defined by VARC classification 2 or 3, and major cardiovascular events defined by the composite of all-cause death, myocardial infarction based on the universal definition, or stroke defined by NeuroARC types 1a or 1d ischemic CNS injury. Additional secondary endpoints include type 1, 2, and 3 VARC classification bleeding, fatal bleeding defined by Type 4 VARC classification, death, cardiovascular death, type 1 myocardial infarction, stroke, intracranial bleeding, transient cerebral ischemic attack, any hospitalization, cardiovascular hospitalization, VARC-defined prosthetic valve thrombosis, and death at 2 years as recorded in the national mortality database.

The trial aims to demonstrate the non-inferiority of the experimental arm, which involves 3 months of therapy with 75 to 100 mg oral **aspirin**, compared to the standard arm, which involves 12 months of therapy with the same dosage. The efficacy parameters will be collected and analyzed at specified timepoints, including a 12-month follow-up after TAVI, to evaluate the outcomes of the treatment regimens.