Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression (SEARCH)

Phase 2RecruitingNCT06922994

Centro Cardiologico Monzino102 enrolled

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

102

Conditions

Arrhythmogenic Cardiomyopathy

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

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

Outcomes

Primary Outcomes

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 (%)

Time frame: From enrollment to the end of treatment at 18 months

Secondary Outcomes

Safety of Atorvastatin treatment

Monitoring of adverse events and patient's well-being.

Time frame: 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)

Time frame: 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)

Time frame: 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 (%)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: From enrollment to the end of treatment (18 months)

Statin Effect on Arrhythmogenic Cardiomyopathy Disease Progression (SEARCH)

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts