Blockade of the Renin-angiotensin-aldosterone System in Patients with ARVD
- Conditions
- Arrhythmogenic Right Ventricular Dysplasia
- Interventions
- Drug: Placebo
- Registration Number
- NCT03593317
- Lead Sponsor
- Hospices Civils de Lyon
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- >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.
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: 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo group Placebo - Spironolactone group Spironolactone -
- Primary Outcome Measures
Name Time Method number of ventricular extrasystoles > 500 on 24h-Holter ECG at year 1 Right ventricle longitudinal strain measured by echocardiography at year 1 Right ventricle infundibulum diameter measured by echocardiography at year 1
- Secondary Outcome Measures
Name Time Method number of palpitations at year 3 left ventricle volumes measured by echocardiography at year 3 Morphologic criterion
number of ventricular extrasystoles on 24h-Holter ECG at year 1 number of sudden death at year 3 number of ventricular tachycardia at year 3 number of syncope at year 3 Dosage of IL6 (Interleukin 6) at year 3 Quantification of inflammation
number of dyspnea at year 3 number of MACE (Major adverse cardiac events) at year 3 left ventricle diameters measured by echocardiography at year 3 Morphologic criterion
number of thoracic pain at year 3 number of hospital admissions at year 3 left ventricle ejection fraction measured by echocardiography at year 3 Morphologic criterion
aneurism measured by echocardiography at year 3 Morphologic criterion
dyskinesia measured by echocardiography at year 3 Morphologic criterion
sustained ventricular tachycardia on 24h Holter ECG at year 1 Rhythmic criterion
evolution of PR interval duration on ECG at year 1 Rhythmic criterion
late potentials measured with high amplification ECG at year 3 Rhythmic criterion
number of ventricular extrasystoles by stress test at year 3 Rhythmic criterion
Left ventricular global longitudinal strain measured by echocardiography at year 1 Morphologic criterion
evolution of QRS width (50mm/s) on ECG at year 1 Morphologic criterion
Number of hospital admissions owing to clinical deterioration at year 3 Evolution of telediastolic right ventricle volume measured by echocardiography at year 3 according to the genotype of desmosome genes
arrhythmia burden measured by 24h Holter ECG at year 3 according to the genotype of desmosome genes
Dosage of MMP9 (Matrix metallopeptidase 9) at year 3 Quantification of fibrosis
Dosage of TIMP2 (Tissue Inhibitory MetalloProtease 2) at year 3 Quantification of fibrosis
number of ventricular extrasystoles on 24h Holter ECG at year 1 Rhythmic criterion
Evolution of functional symptoms by recording adverse events at year 3 Functional criteria
Dosage of TIMP1 (Tissue Inhibitory MetalloProtease 1) at year 3 Quantification of fibrosis
Dosage of IL8 (Interleukin 8) at year 3 Quantification of inflammation
Trial Locations
- Locations (13)
CHU Amiens Picardie
🇫🇷Amiens, France
Hôpital Cardiologique Louis Pradel
🇫🇷Bron, France
Hôpital Gabriel Montpied
🇫🇷Clermont-ferrand, France
CHU Dijon
🇫🇷Dijon, France
Hôpital Michallon
🇫🇷Grenoble, France
Hôpital de la Timone
🇫🇷Marseille, France
Hôpital Arnaud de Villeneuve
🇫🇷Montpellier, France
Hôpital Laennec
🇫🇷Nantes, France
Groupe Hospitalo Universitaire Caremeau
🇫🇷Nimes, France
Hôpital Pitié Salpetrière
🇫🇷Paris, France
Hôpital de Haut-Lévêque
🇫🇷Pessac, France
Nouvel Hôpital Civil
🇫🇷Strasbourg, France
Hôpital Rangueil
🇫🇷Toulouse, France