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

Официальное название

Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD: a Double-blind Multicentre Prospective Randomized Study.

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Right ventricle longitudinal strain measured by echocardiography [Срок оценки: at year 1]
• Right ventricle infundibulum diameter measured by echocardiography [Срок оценки: at year 1]
• number of ventricular extrasystoles > 500 on 24h-Holter ECG [Срок оценки: at year 1]

Вторичные конечные точки (12)

• number of ventricular extrasystoles on 24h-Holter ECG [Срок оценки: at year 1]
• number of palpitations [Срок оценки: at year 1]
• number of palpitations [Срок оценки: at year 3]
• number of ventricular tachycardia [Срок оценки: at year 1]
• number of ventricular tachycardia [Срок оценки: at year 3]
• number of dyspnea [Срок оценки: at year 1]
• number of dyspnea [Срок оценки: at year 3]
• number of syncope [Срок оценки: at year 1]
• number of syncope [Срок оценки: at year 3]
• number of sudden death [Срок оценки: at year 1]
• number of sudden death [Срок оценки: at year 3]
• number of thoracic pain [Срок оценки: at year 1]

Критерии участия

Критерии включения

• >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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Франция · 13 центров

• CHU Amiens Picardie — Amiens
• Hôpital Cardiologique Louis Pradel — Bron
• Hôpital Gabriel Montpied — Clermont-Ferrand
• CHU Dijon — Dijon
• Hôpital Michallon — Grenoble
• Hôpital de la Timone — Marseille
• Hôpital Arnaud de Villeneuve — Montpellier
• Hôpital Laennec — Nantes
• … и ещё 5 центров

Публикации

• Alexandrino FB, Faaborg-Andersen CC, daSilva-deAbreu A. Anticoagulation in patients with atrial fibrillation and heart failure: More than meets the eye? Int J Cardiol. 2024 Feb 15;397:131591. doi: 10.1016/j.ijcard.2023.131591. Epub 2023 Nov 17. No abstract available. PMID 37979797

Идентификаторы

NCT: NCT03593317 · 69HCL18_0038 · 2023-505048-20-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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