Efficacy of Atorvastatin in Mitigating Progression of Arrhythmogenic Cardiomyopathy in Patients: A Randomized, Placebo-Controlled Clinical Trial

The primary objective of this study is to evaluate the **efficacy** of Atorvastatin in preventing functional right ventricular (RV) deterioration in patients with Arrhythmogenic Cardiomyopathy (ACM). This is clinically relevant as ACM is a progressive cardiac condition that can lead to severe arrhythmias and heart failure, and preserving RV function is crucial for patient outcomes.

Secondary objectives include:

• Assessing the efficacy of Atorvastatin in preventing electric, morphological, and biomarker deterioration, which are critical indicators of disease progression and overall cardiac health.
• Evaluating the safety of Atorvastatin treatment, ensuring that the therapeutic benefits outweigh any potential risks associated with its use.

The clinical trial focuses on individuals diagnosed with **Arrhythmogenic Cardiomyopathy (ACM)**, aiming to assess the efficacy of Atorvastatin in preventing functional right ventricular deterioration. The study population includes both male and female participants aged 18 years and older. Participants were selected based on a confirmed diagnosis of ACM according to the 2010 Task Force criteria or Padua Criteria, and all have provided informed consent. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** of **atorvastatin** in preventing the functional deterioration of the right ventricle in patients with **Arrhythmogenic Cardiomyopathy (ACM)**. This study is a Phase IV, randomized, double-blind, placebo-controlled trial. Participants will be randomly assigned to receive either atorvastatin or a placebo, with the treatment administered orally in the form of film-coated tablets. The trial is expected to commence on October 1, 2024, and conclude by August 31, 2026, with a maximum treatment period of 18 months for each participant.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on the 2010 Task Force criteria or Padua Criteria for ACM, age of 18 years or older, and signed informed consent. Following successful screening, participants will be enrolled and randomized into the study. Subsequent follow-up visits will be scheduled at regular intervals to monitor the primary endpoint, which is the deterioration from baseline of the right ventricular free wall longitudinal strain measured by echocardiography. Secondary endpoints include changes in arrhythmia burden, morphological parameters, ECG parameters, and blood parameters, as well as monitoring for adverse events.

The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted to evaluate the long-term effects of atorvastatin on ACM progression. Participant involvement is expected to last up to 18 months, with conditions for early termination including withdrawal of consent, significant adverse events, or any other medical reasons deemed necessary by the investigator. The trial aims to provide valuable insights into the potential benefits of atorvastatin in managing ACM, contributing to improved therapeutic strategies for this condition.

The clinical trial involves the administration of **Atorvastatin**, a lipid-lowering agent, to evaluate its efficacy in preventing functional right ventricular deterioration in patients with arrhythmogenic cardiomyopathy. The experimental medication, **Atorvastatin**, is provided in the form of a film-coated tablet, specifically branded as "Atorvastatina Teva Italia 80 mg compresse rivestite con film." Each tablet contains 80 mg of the active substance **atorvastatin**, which is chemically synthesized. The tablets are administered orally, with a maximum daily dose of 80 mg. The treatment period extends up to 18 months, during which participant compliance is monitored through regular assessments and pill counts to ensure adherence to the dosing schedule.

In addition to the experimental treatment, a placebo is utilized as a comparator in the study. The placebo is presented as film-coated tablets that are white, elliptical in shape, and coated with a smooth film, with dimensions approximately 18.8 mm x 10.3 mm, identical to those containing atorvastatin. The placebo tablets do not contain any active pharmaceutical ingredient and are used to maintain blinding in the trial. The administration of the placebo follows the same oral route and dosing schedule as the atorvastatin tablets, ensuring consistency in the treatment regimen across all study participants.

The efficacy of Atorvastatin in the clinical trial titled "Statin Effect on ARrhythmogenic CardiomyopatHy disease progression" will be assessed through a series of predefined endpoints. The primary endpoint is the deterioration from baseline of right ventricular (RV) free wall longitudinal strain, which will be measured using echocardiography (ECHO). Secondary endpoints include the deterioration from baseline of arrhythmia burden, which encompasses premature ventricular contractions (PVC), non-sustained and sustained ventricular arrhythmias (VA), ventricular fibrillation (VF), and appropriate implantable cardioverter-defibrillator (ICD) shocks. Additionally, changes in other morphological parameters such as ventricular volumes and function, assessed by both ECHO and cardiac magnetic resonance (CMR), will be evaluated. Further secondary endpoints involve the assessment of electrocardiogram (ECG) parameters and blood parameters, alongside the monitoring of adverse events (AE).