Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression (SEARCH) (SEARCH)

Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression

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

Study Overview

• Status: Recruiting
• Conditions: Arrhythmogenic Cardiomyopathy
• Intervention / Treatment: Drug: Atorvastatin 80 mg/day; Drug: Placebo atorvastatin

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elena Sommariva; Phone Number: +39 0258002752; Email: elena.sommariva@cardiologicomonzino.it
• Study Contact Backup: Name: Claudio Tondo; Phone Number: +39 0258002275; Email: claudio.tondo@cardiologicomonzino.it

Study Locations

• Italy
  • Ancona, Italy, 60126
    • Recruiting
    • Università Politecnica delle Marche
    • Contact: Michela Casella; Phone Number: +39 0715965324; Email: m.casella@staff.univpm.it
  • Milano, Italy, 20138
    • Recruiting
    • Centro Cardiologico Monzino IRCSS
    • Contact: Claudio Tondo; Phone Number: +39 0258002275; Email: claudio.tondo@cardiologicomonzino.it
  • Napoli, Italy, 80131
    • Recruiting
    • AORN - Ospedali dei Colli
    • Contact: Giuseppe Limongelli; Phone Number: +39 0817062211; Email: giuseppe.limongelli@ospedalideicolli.it
  • Napoli, Italy, 80138
    • Not yet recruiting
    • Università Degli Studi Di Napoli Federico Ii
    • Contact: Raffaella Lombardi; Phone Number: +39 081676541; Email: raffaella.lombardi@unina.it
  • PV
    • Pavia, PV, Italy, 27100
      • Recruiting
      • Fondazione I.R.C.C.S. Policlinico San Matteo
      • Contact: Annalisa Turco; Phone Number: +390382503158; Email: A.Turco@smatteo.pv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin; Atorvastatin arm will be composed by 51 patients affected by Arrhythmogenic Cardiomyopathy.	Drug: Atorvastatin 80 mg/day; Atorvastatin 80mg/day will be administered for 18 months to patients affected by Arrhythmogenic Cardiomyopathy
Placebo Comparator: Placebo; Placebo arm will be composed by 51 patients affected by Arrhythmogenic Cardiomyopathy.	Drug: Placebo atorvastatin; One tablet of placebo will be administered for 18 months to patients affected by Arrhythmogenic Cardiomyopathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Atorvastatin in avoiding functional right ventricular deterioration	Variation of right ventricular free wall longitudinal strain measured by echocardiography after 18 months respect to baseline (%)	From enrollment to the end of treatment at 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Atorvastatin treatment	Monitoring of adverse events and patient's well-being.	From enrollment to 1 month after the end of treatment (19 months)
Efficacy of Atorvastatin in avoiding morphological deterioration (ventricular volumes)	Deterioration from baseline of other morphological parameters measured both at echocardiography and cardiac magnetic resonance: ventricular volumes (ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding morphological deterioration (wall thickness )	Deterioration from baseline of other morphological parameters measured both at echocardiography and cardiac magnetic resonance: wall thickness (mm)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding morphological deterioration (cardiac function )	Deterioration from baseline of other morphological parameters measured both at echocardiography and cardiac magnetic resonance: cardiac function (%)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding arrhythmic deterioration (premature ventricular contractions)	Deterioration from baseline of arrhythmia burden: premature ventricular contractions (number in the 24h)	From enrollment to the end of treatment at 18 months
Efficacy of Atorvastatin in avoiding arrhythmic deterioration (nonsustained ventricular arrhythmias)	Deterioration from baseline of arrhythmia burden: nonsustained ventricular arrhythmias (number)	From enrollment to the end of treatment at 18 months
Efficacy of Atorvastatin in avoiding arrhythmic deterioration (sustained ventricular arrhythmias)	Deterioration from baseline of arrhythmia burden: sustained ventricular arrhythmias (number)	From enrollment to the end of treatment at 18 months
Efficacy of Atorvastatin in avoiding arrhythmic deterioration (ventricular fibrillation )	Deterioration from baseline of arrhythmia burden: ventricular fibrillation (number)	From enrollment to the end of treatment at 18 months
Efficacy of Atorvastatin in avoiding arrhythmic deterioration (ICD shocks)	Deterioration from baseline of arrhythmia burden: appropriate ICD shocks (number)	From enrollment to the end of treatment at 18 months
Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (QRS)	Deterioration from baseline of electrocardiographic parameters: QRS duration (ms)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (QT)	Deterioration from baseline of electrocardiographic parameters: QT duration (ms)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (PR)	Deterioration from baseline of electrocardiographic parameters: PR duration (ms)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (amplitudes)	Deterioration from baseline of electrocardiographic parameters: amplitude of the potential (mV)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (T wave)	Deterioration from baseline of electrocardiographic parameters: ), T wave inversion (number of presences in V1-V6)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding electrocardiographic deterioration (ԑ wave)	Deterioration from baseline of electrocardiographic parameters: ԑ wave in V1-V3 (presence)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (oxLDL)	Deterioration from baseline of blood parameters: oxLDL (mU/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (MDA)	Deterioration from baseline of blood parameters: MDA (ng/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (4HNE)	Deterioration from baseline of blood parameters: 4HNE (pg/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (estradiol)	Deterioration from baseline of blood parameters: estradiol (pg/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (testosterone)	Deterioration from baseline of blood parameters: testosterone (ng/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (BIN1)	Deterioration from baseline of blood parameters: BIN1 (pg/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (GAL3)	Deterioration from baseline of blood parameters: GAL3 (ng/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (HSP70)	Deterioration from baseline of blood parameters: HSP70 (ng/mL)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (TGFb)	Deterioration from baseline of blood parameters: TGFb (pg/mL)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (ST2)	Deterioration from baseline of blood parameters: ST2 (ng/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (BNP)	Deterioration from baseline of blood parameters: BNP (pg/mL)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (NTproBNP)	Deterioration from baseline of blood parameters: NTproBNP (pg/mL)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (hs-cTnI)	Deterioration from baseline of blood parameters: hs-cTnI (ng/L)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (CRP)	Deterioration from baseline of blood parameters: CRP (mg/L)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (IL6)	Deterioration from baseline of blood parameters: IL6 (pg/ml)	From enrollment to the end of treatment (18 months)
Efficacy of Atorvastatin in avoiding biomarkers deterioration (TNF alfa)	Deterioration from baseline of blood parameters: TNF alfa (pg/ml)	From enrollment to the end of treatment (18 months)

Collaborators and Investigators

• Sponsor: Centro Cardiologico Monzino
• Collaborators: Federico II University; Università Politecnica delle Marche; Ospedali dei Colli
• Investigators: Principal Investigator: Claudio Tondo, Centro Cardiologico Monzino IRCCS

Publications and helpful links

General 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 new pathogenic trigger in arrhythmogenic cardiomyopathy. EMBO Mol Med. 2021 Sep 7;13(9):e14365. doi: 10.15252/emmm.202114365. Epub 2021 Aug 2.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 11, 2025

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Atorvastatin; Arrhythmias; Strain; Disease progression risk
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease Attributes; Disease Progression; Cardiomyopathies; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: SEARCH; PNRR-MCNT2-2023-12376978 (Other Grant/Funding Number: European Union - NextGenerationEU); 2024-514643-28-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No