Evaluation of Rivaroxaban for Antithrombotic Management in Patients with Hypertrophic Cardiomyopathy and Abnormal Left Atrial Reservoir Strain

The primary objective of this study is to demonstrate that **antithrombotic** treatment is superior to standard management in patients with **Hypertrophic Cardiomyopathy** (HCM) who have an abnormal Left Atrial Reservoir Strain (LARS). This is clinically relevant as it aims to improve the management of thromboembolic risk in HCM patients, potentially reducing the incidence of stroke and other thromboembolic events.

Secondary objectives include:

• Testing the homogeneity of the intervention effect on all components of the primary composite outcome.
• Describing atrial arrhythmias and their relation to documented ischemic events.
• Comparing changes in Left Atrial reservoir strain.
• Assessing quality of life.

The clinical trial involves participants diagnosed with **hypertrophic cardiomyopathy**. The study population includes both male and female subjects, aged between 18 and 80 years, who are in sinus rhythm and have a prior confirmed diagnosis of primary hypertrophic cardiomyopathy. Participants must have a left atrial reservoir strain measured at 20% or less, confirmed by a core laboratory. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. All participants are required to provide informed consent. No specific lifestyle considerations such as diet or physical activity are mentioned for this trial.

The clinical trial is designed to evaluate the efficacy of **rivaroxaban** in the management of patients with **hypertrophic cardiomyopathy** (HCM) who exhibit an abnormal Left Atrial Reservoir Strain (LARS). This trial is a randomized, double-blind, controlled study aimed at demonstrating that antithrombotic treatment is superior to standard management in this patient population. The trial is set to commence recruitment on September 15, 2025, and is expected to conclude by September 15, 2030, with a total duration of approximately five years.

Participants will be involved in the study for a maximum treatment period of 24 months. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age (18-80 years), sinus rhythm, and a prior confirmed diagnosis of primary hypertrophic cardiomyopathy with LARS ≤20%. Following the screening, participants will be randomized to receive either 15 mg or 20 mg of rivaroxaban in the form of film-coated tablets, administered orally. Regular follow-up visits will be scheduled to monitor the participants' health status, adherence to the medication regimen, and to assess primary and secondary endpoints, including composite endpoints of death, ischemic events, and bleeding.

The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse events, fail to adhere to the study protocol, or withdraw consent. The primary endpoint of the study is a composite of clinical outcomes, including death, myocardial infarction, stroke, systemic embolism, and bleeding events. Secondary endpoints will further evaluate bleeding classifications, ischemic events, atrial arrhythmias, and quality of life measures using the Kansas City Cardiomyopathy Questionnaire (KCCQ).

The clinical trial involves the administration of **Rivaroxaban**, a direct oral anticoagulant, in two different dosages. The first experimental medication is **Rivaroxaban EG 15 mg**, presented as a film-coated tablet. This pharmaceutical form is designed for **oral use**. The maximum daily dose for this formulation is 15 mg, with a total maximum dose of 10,950 mg over a treatment period of up to 24 months. The active substance, **Rivaroxaban**, is of chemical origin and is known by several synonyms, including BAY59-7939 and JNJ-39039039. The medication is manufactured by EG Labo Laboratoires Eurogenerics and is authorized for use in France under the marketing authorization number 34009 302 656 5 9.

The second experimental medication is **Rivaroxaban EG 20 mg**, also in the form of a film-coated tablet for **oral use**. The maximum daily dose for this formulation is 20 mg, with a total maximum dose of 14,600 mg over a treatment period of up to 24 months. Like the 15 mg formulation, the active substance is **Rivaroxaban**, and it shares the same chemical origin and synonyms. This medication is also produced by EG Labo Laboratoires Eurogenerics and holds the marketing authorization number 34009 302 656 8 0 in France.

Both formulations are part of a clinical trial aimed at evaluating the efficacy of antithrombotic treatment in patients with hypertrophic cardiomyopathies, specifically those with an abnormal Left Atrial Reservoir Strain (LARS). The trial seeks to demonstrate the superiority of this treatment over standard management practices. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

The efficacy of the clinical trial titled "LA-HCM: Direct oral anticoagulant for Antithrombotic Management in patients with Hypertrophic Cardiomyopathies" will be assessed using a combination of primary and secondary endpoints. The primary endpoint is a composite measure that includes a net clinical endpoint of death, a composite ischemic endpoint comprising **myocardial infarction**, stroke (including asymptomatic events documented on magnetic resonance imaging), systemic embolism, and bleeding events classified as ISTH major and non-major clinically relevant bleeding.

Secondary endpoints will further evaluate efficacy through additional composite measures. These include components of the primary composite outcome such as bleeding events (assessed using the ISTH-SSC Bleeding Assessment Tool and BARC classifications), ischemic endpoints, and all-cause death. Other secondary endpoints include the identification of atrial arrhythmias through ECG/holter monitoring, measurement of Left Atrial reservoir strain, and patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ).