Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression (SEARCH)

Official title

Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression

Overview

The goal of this clinical trial is to learn if Atorvastatin 80 mg is effective to avoid functional right ventricular deterioration in patients affected by Arrhythmogenic Cardiomyopathy. It will also learn about the safety of Atorvastatin 80 mg in this type of patients. The main questions it aims to answer are: 1. Does Atorvastatin 80 mg prevent worstening of the right ventricular functioning? 2. Does Atorvastatin 80 mg prevent the worsening of electric, morphological and biomarkers deterioration? 3. What medical problems do participants have when taking Atorvastatin 80 mg? Researchers will compare Atorvastatin 80 mg to a placebo (a look-alike substance that contains no drug) to see if the drug works to treat Arrhythmogenic Cardiomyopathy. Participants will: 1. Take Atorvastatin 80 mg or a placebo every day for 18 months; 2. Visit the clinic at the enrollment and after 2, 4, 9 and 18 months for checkups and tests; 3. Make a phone call for safety check after 12, 15 and 19 months since the enrollment; 4. Fill out psychological questionnaires

Interventions

• Drug Atorvastatin 80 mg/day
  Atorvastatin 80mg/day will be administered for 18 months to patients affected by Arrhythmogenic Cardiomyopathy
• Drug Placebo atorvastatin
  One tablet of placebo will be administered for 18 months to patients affected by Arrhythmogenic Cardiomyopathy

Primary outcome measures

• Efficacy of Atorvastatin in avoiding functional right ventricular deterioration [Time frame: From enrollment to the end of treatment at 18 months]

Secondary outcome measures (12)

• Safety of Atorvastatin treatment [Time frame: From enrollment to 1 month after the end of treatment (19 months)]
• Efficacy of Atorvastatin in avoiding morphological deterioration (ventricular volumes) [Time frame: From enrollment to the end of treatment (18 months)]
• Efficacy of Atorvastatin in avoiding morphological deterioration (wall thickness ) [Time frame: From enrollment to the end of treatment (18 months)]
• Efficacy of Atorvastatin in avoiding morphological deterioration (cardiac function ) [Time frame: From enrollment to the end of treatment (18 months)]
• Efficacy of Atorvastatin in avoiding arrhythmic deterioration (premature ventricular contractions) [Time frame: From enrollment to the end of treatment at 18 months]
• Efficacy of Atorvastatin in avoiding arrhythmic deterioration (nonsustained ventricular arrhythmias) [Time frame: From enrollment to the end of treatment at 18 months]
• Efficacy of Atorvastatin in avoiding arrhythmic deterioration (sustained ventricular arrhythmias) [Time frame: From enrollment to the end of treatment at 18 months]
• Efficacy of Atorvastatin in avoiding arrhythmic deterioration (ventricular fibrillation ) [Time frame: From enrollment to the end of treatment at 18 months]
• Efficacy of Atorvastatin in avoiding arrhythmic deterioration (ICD shocks) [Time frame: From enrollment to the end of treatment at 18 months]
• Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (QRS) [Time frame: From enrollment to the end of treatment (18 months)]
• Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (QT) [Time frame: From enrollment to the end of treatment (18 months)]
• Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (PR) [Time frame: From enrollment to the end of treatment (18 months)]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Known hypersensitivity to atorvastatin or any of the excipients
• Moderate or severe liver disease
• Muscle disease
• Left ventricular ejection fraction <35%
• Congestive heart failure defined by the New York Heart Association (NYHA) as class III or IV.
• Known cardiomyopathy of other origin: post ischemic, hypertrophic, idiopathic dilated, restrictive; known moderate-to-severe mitral or aortic valvulopathy; pulmonary hypertension; congenital cardiac abnormalities
• Hypercholesterolemic patients that require the use of lipid lowering drugs.
• Heart transplantation
• Estimated life expectancy of less than 2 years
• 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
• Potent CYP3A4 modifiers such as Erythromycin, Clarithromycin Azole antifungals, Protease inhibitors , Gemfibrozil, Ciclosporin, Danazol
• Fusidic acid (drug for bacterial infections)
• Hepatitis C antivirals as telaprevir, boceprevir, glecaprevir/pibrentasvir and ledipasvir/sofosbuvir combination
• 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
• Drugs primary indicated as antioxidants
• 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.
• Pregnant or lactating women
• Women of childbearing age who are not using adequate contraception
• Known dependency on alcohol - drug abuse.
• Contraindications to cardiac magnetic resonance

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Italy · 5 centers

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

Publications

• Sommariva E, Stadiotti I, Casella M, Catto V, Dello Russo A, Carbucicchio C, Arnaboldi L, De Metrio S, Milano G, Scopece A, Casaburo M, Andreini D, Mushtaq S, Conte E, Chiesa M, Birchmeier W, Cogliati E, Paolin A, Konig E, Meraviglia V, De Musso M, Volani C, Cattelan G, Rauhe W, Turnu L, Porro B, Pedrazzini M, Camera M, Corsini A, Tondo C, Rossini A, Pompilio G. Oxidized LDL-dependent pathway as n PMID 34337880

Identifiers

NCT: NCT06922994 · SEARCH · PNRR-MCNT2-2023-12376978 · 2024-514643-28-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗