Comparative Study of Short-Term Dabigatran Etexilate Versus Antiplatelet Therapy in Preventing Device Thrombosis Post-Left Atrial Appendage Closure in Atrial Fibrillation

The primary objective of the study is to compare the incidence of **device thrombosis** following Left Atrial Appendage Closure (LAAC) between patients receiving short-term (8 weeks) anticoagulation therapy with Direct Oral Anticoagulants (DOACs) versus antiplatelet therapy. This comparison is clinically relevant as it aims to determine the most effective strategy for preventing device thrombosis, a significant complication that can occur after LAAC in patients with **atrial fibrillation**. The study's findings could influence clinical decision-making regarding post-procedural management to optimize patient outcomes and reduce thrombotic events.

The clinical trial involves a total of **250 participants** diagnosed with **Atrial Fibrillation** and device thrombosis post-Left Atrial Appendage Closure. The study population includes both male and female subjects, aged **18 years and older**, who have undergone successful Left Atrial Appendage Closure (LAAC) with any approved device. Participants were selected based on their eligibility to receive either short-term anticoagulation therapy or antiplatelet therapy, as part of the trial's objective to compare the incidence of device thrombosis following LAAC. The trial does not include vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria. The sponsor has not provided additional information regarding the general health status or lifestyle habits of the participants.

The clinical trial is designed to evaluate the efficacy and safety of short-term anticoagulation therapy compared to antiplatelet therapy in preventing device thrombosis following left atrial appendage closure (LAAC) in patients with **atrial fibrillation**. This trial is a randomized, double-blind, controlled study, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to last approximately eight weeks, with the primary endpoint being the incidence of device thrombosis as evaluated by transesophageal echocardiography (TEE) 60 days post-LAAC. The trial will also assess safety endpoints, including adverse clinical events such as all-cause mortality, stroke, bleeding, or device thrombosis within the same period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as successful LAAC and age of 18 years or older. Following randomization, participants will attend follow-up visits at two months, where primary and secondary endpoints will be evaluated. The end-of-study visit will occur at the conclusion of the eight-week treatment period, during which final assessments will be conducted. The total duration of participant involvement is anticipated to be approximately eight weeks, aligning with the maximum treatment period for the medications involved, which include **dabigatran etexilate**, **acetylsalicylic acid**, **clopidogrel**, **apixaban**, **edoxaban**, and **rivaroxaban**.

Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial is classified as a low-intervention clinical trial, as it involves the use of authorized medicinal products in accordance with their marketing authorizations, posing no additional risk beyond routine clinical practice. The trial is set to commence recruitment on January 30, 2025, with an estimated end date of June 25, 2025.

The clinical trial involves the administration of several **experimental medications** to evaluate their efficacy in preventing device thrombosis following left atrial appendage closure. The first experimental medication is **Dabigatran Etexilate**, provided in the form of 150 mg hard capsules. This medication is administered orally with a maximum daily dose of 150 mg. The treatment period for this medication is set at 8 weeks. Dabigatran Etexilate is a chemical substance produced by Galenicum Health, S.L.

Another medication used in the trial is **Aspirine Arrow**, which contains **acetylsalicylic acid** as the active ingredient. It is available as 75 mg gastro-resistant tablets and is also administered orally. The maximum daily dose for Aspirine Arrow is 125 mg, with a treatment duration of 8 weeks. This chemical substance is manufactured by Arrow Generiques.

**Clopidogrel Viatris** is included in the study as a 75 mg film-coated tablet. The active substance, **clopidogrel**, is administered orally with a maximum daily dose of 75 mg over an 8-week period. This chemical compound is produced by Viatris Limited.

The trial also involves the use of **Apixaban Teva GmbH**, which is provided as 5 mg film-coated tablets. The active substance, **apixaban**, is administered orally with a maximum daily dose of 5 mg for a duration of 8 weeks. This chemical substance is manufactured by Teva GmbH.

**Edoxaban TAD** is another medication used in the trial, available as 60 mg film-coated tablets. The active ingredient, **edoxaban**, is administered orally with a maximum daily dose of 60 mg over an 8-week period. This chemical compound is produced by TAD Pharma GmbH.

Lastly, the trial includes **Rivaroxaban Kéri**, which is provided as 20 mg film-coated tablets. The active substance, **rivaroxaban**, is administered orally with a maximum daily dose of 20 mg for a treatment period of 8 weeks. This chemical substance is manufactured by Kéri Pharma Hungary Kft.

All medications in this trial are administered orally, and participant compliance is monitored throughout the study to ensure adherence to the dosing schedules. The trial aims to compare the incidence of device thrombosis between patients receiving short-term anticoagulation therapy and those receiving antiplatelet therapy.

The efficacy of the clinical trial titled "Short-Term Anticoagulation versus Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure" (ANDES study) will be assessed using specific primary and secondary endpoints. The primary efficacy endpoint is the occurrence of device thrombosis, which will be evaluated by transesophageal echocardiography (TEE) 60 days after left atrial appendage closure (LAAC) and analyzed in a central echo core lab. This assessment will follow an as-treated analysis approach. The primary safety endpoint includes adverse clinical events such as all-cause mortality, stroke, bleeding, or device thrombosis within 60 days post-LAAC, evaluated through an intention-to-treat analysis.

Secondary endpoints include the evaluation of device thrombosis using TEE or computed tomography 12 months after LAAC. Additionally, ischemic events, including stroke and transient ischemic attack (TIA), will be monitored at 2 months and annually up to 5 years. Bleeding events will also be assessed at similar intervals. These endpoints will provide comprehensive data on the efficacy and safety of the therapeutic strategies being compared in the trial. The trial is designed to compare the incidence of device thrombosis between patients receiving short-term anticoagulation therapy with direct oral anticoagulants (DOACs) and those receiving antiplatelet therapy.