Clinical trial NCT06922994: Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression (SEARCH)
Official title: Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Arrhythmogenic Cardiomyopathy
Keywords: Atorvastatin
Strain
Disease progression risk
Arrhythmias
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
Collaborators: name: Federico II University
name: Università Politecnica delle Marche
name: Ospedali dei Colli
First posted: 2025-04-11
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter, prospective, randomized, clinical study: Atorvastatin 80mg/day or placebo will be administered for 18 months to 102 ACM patients, and the endpoints will be tested.
Primary purpose: TREATMENT

Brief summary: 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


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

Primary outcomes:
measure: Efficacy of Atorvastatin in avoiding functional right ventricular deterioration
timeFrame: From enrollment to the end of treatment at 18 months
Secondary outcomes:
measure: Safety of Atorvastatin treatment
timeFrame: From enrollment to 1 month after the end of treatment (19 months)
measure: Efficacy of Atorvastatin in avoiding morphological deterioration (ventricular volumes)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding morphological deterioration (wall thickness )
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding morphological deterioration (cardiac function )
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding arrhythmic deterioration (premature ventricular contractions)
timeFrame: From enrollment to the end of treatment at 18 months
measure: Efficacy of Atorvastatin in avoiding arrhythmic deterioration (nonsustained ventricular arrhythmias)
timeFrame: From enrollment to the end of treatment at 18 months
measure: Efficacy of Atorvastatin in avoiding arrhythmic deterioration (sustained ventricular arrhythmias)
timeFrame: From enrollment to the end of treatment at 18 months
measure: Efficacy of Atorvastatin in avoiding arrhythmic deterioration (ventricular fibrillation )
timeFrame: From enrollment to the end of treatment at 18 months
measure: Efficacy of Atorvastatin in avoiding arrhythmic deterioration (ICD shocks)
timeFrame: From enrollment to the end of treatment at 18 months
measure: Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (QRS)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (QT)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (PR)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (amplitudes)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (T wave)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (ԑ wave)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (oxLDL)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (MDA)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (4HNE)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (estradiol)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (testosterone)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (BIN1)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (GAL3)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (HSP70)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (TGFb)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (ST2)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (BNP)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (NTproBNP)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (hs-cTnI)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (CRP)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (IL6)
timeFrame: From enrollment to the end of treatment (18 months)
measure: Efficacy of Atorvastatin in avoiding biomarkers deterioration (TNF alfa)
timeFrame: From enrollment to the end of treatment (18 months)
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Università Politecnica delle Marche
city: Milano
country: Italy
facility: Centro Cardiologico Monzino IRCSS
city: Napoli
country: Italy
facility: AORN - Ospedali dei Colli
city: Napoli
country: Italy
facility: Università degli Studi di Napoli Federico II
Study officials:
affiliation: Centro Cardiologico Monzino IRCCS
name: Claudio Tondo
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 new pathogenic trigger in arrhythmogenic cardiomyopathy. EMBO Mol Med. 2021 Sep 7;13(9):e14365. doi: 10.15252/emmm.202114365. Epub 2021 Aug 2.