Evaluation of Hemostasis in Patients Undergoing Percutaneous Closure of Patent Foramen Ovale or Atrial Septal Defect: Rivaroxaban Versus Clopidogrel and Acetylsalicylic Acid

The primary objective of this study is to evaluate **hemostasis**, specifically focusing on coagulation activation, thrombin generation, and platelet reactivity, following catheter-based closure of **patent foramen ovale** or **atrial septal defect**. This evaluation is clinically relevant as it aims to determine the differences in post-procedural regimens, specifically dual antiplatelet therapy (DAPT) and rivaroxaban, which could influence patient outcomes and guide therapeutic decisions in managing these conditions. The study does not list any secondary objectives.

The clinical trial involves participants diagnosed with **patent foramen ovale** or atrial septal defect. The study population includes both male and female subjects aged 18 years or older. Participants are required to be in general good health, as they must be scheduled for a percutaneous closure of a patent foramen ovale or atrial septal defect, as indicated by their treating physician. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. Selection criteria include the ability to understand and willingness to provide written informed consent. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate **hemostasis** following catheter-based closure of **patent foramen ovale** or **atrial septal defect**. This study is a randomized, double-blind, controlled trial, categorized as a Phase 4 therapeutic exploratory study. The trial will compare the effects of dual antiplatelet therapy (DAPT) and **rivaroxaban** on coagulation activation, thrombin generation, and platelet reactivity. The trial is expected to commence recruitment on April 29, 2024, and conclude by January 1, 2026.

Participants will be involved in the study for a maximum of 12 months, depending on the treatment group. The study will include an initial screening visit to confirm eligibility, where participants must be 18 years or older and scheduled for percutaneous closure of a PFO or ASD. Following the screening, participants will be randomized to receive either **Xarelto** 20 mg film-coated tablets, **Plavix** 75 mg film-coated tablets, or **acetylsalicylic acid** with **caffeine citrate**. The treatment will be administered orally, with the maximum daily doses being 20 mg, 150 mg, and 100 mg, respectively.

Study visits will be scheduled at regular intervals to monitor the primary endpoints, which include coagulation activation markers such as prothrombin fragment 1+2, thrombin antithrombin III complex, and platelet activation markers like P-selectin and CD40 ligand. Additional endpoints include Von Willebrand Factor Antigen, beta-thromboglobulin, plasminogen activator inhibitor-1, D-dimer, thrombin generation test, and anti-Xa activity. The end-of-study visit will assess the overall outcomes and any adverse events.

Participants may be withdrawn from the study if they experience significant adverse effects, are unable to comply with the study protocol, or withdraw consent. The trial aims to provide valuable insights into the comparative efficacy of DAPT and rivaroxaban in managing hemostasis post-procedure, contributing to optimized therapeutic strategies for patients undergoing these interventions.

The clinical trial involves the administration of **Xarelto** 20 mg film-coated tablets, which contain the active substance **rivaroxaban**. Rivaroxaban is a chemical compound with the synonyms BAY59-7939 and JNJ-39039039. The pharmaceutical form is a film-coated tablet, and the medication is administered orally. The maximum daily dose is 20 mg, with a total maximum dose of 660 mg over a treatment period of up to 5 days. The medication is produced by Bayer AG and is not a pediatric formulation.

Another treatment used in the study is **Plavix** 75 mg film-coated tablets, containing the active substance **clopidogrel**. Clopidogrel is also a chemical compound, and the tablets are administered orally. The maximum daily dose for Plavix is 150 mg, with a total maximum dose of 25.50 g over a treatment period of up to 12 months. This medication is manufactured by Sanofi Winthrop Industrie and is not formulated for pediatric use.

The study also includes a comparator treatment involving **acetylsalicylic acid** and **caffeine citrate**. This combination is provided in a dispersible tablet form, administered orally. The maximum daily dose of acetylsalicylic acid is 100 mg, with a total maximum dose of 36,500 mg over a treatment period of up to 5 days. Both active substances are of chemical origin. The dispersible tablet is not a pediatric formulation.

The efficacy of the clinical trial will be assessed by evaluating hemostatic endpoints following catheter-based closure of patent foramen ovale or atrial septal defect. The primary endpoints include the measurement of **coagulation activation** parameters such as prothrombin fragment 1+2 and thrombin antithrombin III complex. Additionally, platelet activation will be assessed through markers like P-selectin and CD40 ligand. Other hemostatic markers to be evaluated include Von Willebrand Factor Antigen (VWF Ag), beta-thromboglobulin (beta-TG), plasminogen activator inhibitor-1 (PAI-1), D-dimer, Thrombin Generation Test, and Anti Xa activity.