Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD

NCT03593317 | Recruiting Phase 2 DMC

• 2 other identifiers: 69HCL18_00382023-505048-20-00
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 13

Brief Summary

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia. Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of the RV function in patients with ARVD. The investigator's hypothesis is that the use of anti-fibrotic medications will prevent or at least reduce the deterioration of the RV function. The aim of this project is to evaluate the effect of spironolactone, a Potassium-sparing diuretic on ventricular myocardial remodeling and on arrhythmia burden in patients with ARVD. The trial is a double-blind parallel multicenter prospective randomized phase II drug study. Patients will be randomized in the two groups: spironolactone or placebo. 13 centers in France will enroll the 120 patients (60 per group). Patients will be followed for 3 years (6 months, 1 year and 3 years) with all examinations (ECG, HA ECG, 24-hour Holter, trans-thoraciqc echocardiography (TTE), biological analyses) according to standard of care. A decrease in right and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with spironolactone. This reduction will improve the quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.

Conditions

Arrhythmogenic Right Ventricular Dysplasia

Keywords

Heart Failure; Right ventricle

Outcome Measures

Primary Outcomes (3)

• Right ventricle longitudinal strain measured by echocardiography

  at year 1

• Right ventricle infundibulum diameter measured by echocardiography

  at year 1

• number of ventricular extrasystoles > 500 on 24h-Holter ECG

  at year 1

Secondary Outcomes (48)

• number of ventricular extrasystoles on 24h-Holter ECG

  at year 1

• number of palpitations

  at year 1

• number of palpitations

  at year 3

• number of ventricular tachycardia

  at year 1

• number of ventricular tachycardia

  at year 3

Study Arms (2)

Spironolactone group

EXPERIMENTAL

Drug: Spironolactone

Placebo group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

Placebo will be taken once a day at the same time of day. The duration of treatment for each patient is 12 months.

Placebo group

Spironolactone DRUG

The doses used in the study are the doses used in standard clinical practice. Initial dose is 25 mg/day until study end . The duration of treatment for each patient is 12 months.

Spironolactone group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18years old
• Diagnosis of ARVD based on Task Force criteria. Two major criteria: 1 morphologic and one rhythmic or 1 major and 2 minor criteria established by the European Society of Cardiology/International Society and Federation of Cardiology.
• Left Ventricular Ejection Fraction \>40%
• Written informed consent.

You may not qualify if:

• Patients under judicial protection.
• Female patient who is pregnant or lactating, or is of child bearing potential (defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤ 55 years or 12 months if \> 55 years) and who did not agree to use highly effective methods of birth control throughout the study.
• No health insurance.
• Right heart failure patient (RV volume\>150ml).
• Spironolactone contraindication: anuria, hyperkalemia (K+\>5 mmol/l), renal failure (DFGCréat\>22 mL/min/1,73 m2), end-stage liver failure, Addison's Disease, hypersensitivity to spironolactone or to any of the excipients (patients with galactose intolerance, lapp lactase deficiency or glucose or galactose malabsorption syndrome), association with eplerenone, association with other hyperkalemic diuretics, association with potassium salts, not recommended in cirrhotic patients (natraemia\<125 mmol/l) or in patients likely to present an acidosis.
• Mandatory indication for a combination of ACE inhibitor and sartan or renin inhibitor (each authorized separately).
• Acute phase of systemic disease.
• Uncompensated hypothyroidism.
• Acute hyperthyroidism.
• Normal right ventricular volume.
• Heart transplantation.
• Swallowing disorders.
• Participation in any other interventional clinical investigation that may have an impact on our study.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (13)

CHU Amiens Picardie

Amiens, France

NOT YET RECRUITING

Hôpital Cardiologique Louis Pradel

Bron, France

RECRUITING

Hôpital Gabriel Montpied

Clermont-Ferrand, France

NOT YET RECRUITING

CHU Dijon

Dijon, France

RECRUITING

Hôpital Michallon

Grenoble, France

NOT YET RECRUITING

Hôpital de la Timone

Marseille, France

NOT YET RECRUITING

Hôpital Arnaud de Villeneuve

Montpellier, France

RECRUITING

Hôpital Laennec

Nantes, France

RECRUITING

Groupe Hospitalo Universitaire Caremeau

Nîmes, France

NOT YET RECRUITING

Hôpital Pitié Salpetrière

Paris, France

RECRUITING

Hôpital de Haut-Lévêque

Pessac, France

NOT YET RECRUITING

Nouvel Hôpital Civil

Strasbourg, France

NOT YET RECRUITING

Hôpital Rangueil

Toulouse, France

NOT YET RECRUITING

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Heart Failure

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiomyopathies; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Philippe Chevalier, MD, PhD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roucher Aude, PhD

CONTACT

426739447; aude.roucher@chu-lyon.fr

Philippe Chevalier, MD, PhD

CONTACT

4 72 35 70 27; philippe.chevalier@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 20, 2018
• Study Start: December 20, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

FR (13)