Atorvastatin 80 mg to slow progression of arrhythmogenic cardiomyopathy

Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression

This trial will try daily high-dose atorvastatin (80 mg) versus placebo in adults with arrhythmogenic cardiomyopathy to see if it prevents right ventricular functional decline and related electrical and structural worsening.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 102 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centro Cardiologico Monzino (Academic / other)
• Locations: 5 sites (Pavia, PV and 4 other locations)
• Trial ID: NCT06922994 on ClinicalTrials.gov

What this trial studies

This Phase 2, randomized, double-blind, placebo-controlled trial gives adults with arrhythmogenic cardiomyopathy either atorvastatin 80 mg daily or a matching placebo for 18 months. Participants attend clinic visits at baseline and 2, 4, 9, and 18 months with additional safety phone checks, and undergo imaging, electrical testing, and biomarker sampling to track disease progression. The primary focus is on preventing right ventricular functional deterioration, with secondary assessments of electrical, morphological, and biomarker changes. Safety and adverse events related to high-dose atorvastatin in this population are recorded throughout the study.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) diagnosed with arrhythmogenic cardiomyopathy by task force criteria who do not require chronic lipid-lowering therapy and who do not have severe liver disease, significant muscle disease, or advanced heart failure.

Not a fit: Patients with severe liver or muscle disease, left ventricular ejection fraction <35%, NYHA class III–IV heart failure, other primary cardiomyopathies, or those already requiring lipid-lowering drugs are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, atorvastatin 80 mg could slow or prevent right ventricular deterioration and reduce progression-related arrhythmic risk in people with arrhythmogenic cardiomyopathy.

How similar studies have performed: Using high-dose statins to slow structural or electrical progression in arrhythmogenic cardiomyopathy is largely novel, with limited direct trial evidence to date though statins have shown benefit in other cardiovascular conditions.

Eligibility criteria

Inclusion Criteria:

1. Participant must be at least 18 years of age, at the time of signing the informed consent
2. Participants affected by Arrhythmogenic Cardiomyopathy as defined by task force criteria

Exclusion Criteria:

1. Known hypersensitivity to atorvastatin or any of the excipients
2. Moderate or severe liver disease
3. Muscle disease
4. Left ventricular ejection fraction \<35%
5. Congestive heart failure defined by the New York Heart Association (NYHA) as class III or IV.
6. Known cardiomyopathy of other origin: post ischemic, hypertrophic, idiopathic dilated, restrictive; known moderate-to-severe mitral or aortic valvulopathy; pulmonary hypertension; congenital cardiac abnormalities
7. Hypercholesterolemic patients that require the use of lipid lowering drugs.
8. Heart transplantation
9. Estimated life expectancy of less than 2 years
10. Any other medical condition that, in the judgment of the investigator, places the patient at risk or makes the patient unreliable or limits the patient's ability to complete the study
11. Potent CYP3A4 modifiers such as Erythromycin, Clarithromycin Azole antifungals, Protease inhibitors , Gemfibrozil, Ciclosporin, Danazol
12. Fusidic acid (drug for bacterial infections)
13. Hepatitis C antivirals as telaprevir, boceprevir, glecaprevir/pibrentasvir and ledipasvir/sofosbuvir combination
14. Any other lipid lowering drugs such as Statins, Cholesterol absorption inhibitors, Bile acid sequestrants , PCSK9 inhibitors, Adenosine triphosphate-citrate lyase inhibitors , Fibrates, Omega-3 fatty acid ethyl esters
15. Drugs primary indicated as antioxidants
16. Enrollment in another clinical trial or past clinical trial in which an investigational drug was administered within 30 days of Visit 1 or within the 5 half-lives of the investigational drug, whichever is longer.
17. Pregnant or lactating women
18. Women of childbearing age who are not using adequate contraception
19. Known dependency on alcohol - drug abuse.
20. Contraindications to cardiac magnetic resonance

Where this trial is running

Pavia, PV and 4 other locations

• Fondazione I.R.C.C.S. Policlinico San Matteo — Pavia, Pv, Italy (Recruiting)
• Università Politecnica delle Marche — Ancona, Italy (Recruiting)
• Centro Cardiologico Monzino IRCSS — Milan, Italy (Recruiting)
• AORN - Ospedali dei Colli — Naples, Italy (Recruiting)
• Università degli Studi di Napoli Federico II — Naples, Italy (Not_yet_recruiting)

Study contacts

• Principal investigator: Claudio Tondo — Centro Cardiologico Monzino IRCCS
• Study coordinator: Elena Sommariva

Conditions Arrhythmogenic Cardiomyopathy; Atorvastatin; Strain; Disease progression risk; Arrhythmias