Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD: a Double-blind Multicentre Prospective Randomized Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 13
- 主要终点
- Right ventricle longitudinal strain measured by echocardiography
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>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.
排除标准
- •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.
研究组 & 干预措施
Spironolactone group
干预措施: Spironolactone (Drug)
Placebo group
干预措施: Placebo (Drug)
结局指标
主要结局
Right ventricle longitudinal strain measured by echocardiography
时间窗: at year 1
Right ventricle infundibulum diameter measured by echocardiography
时间窗: at year 1
number of ventricular extrasystoles > 500 on 24h-Holter ECG
时间窗: at year 1
次要结局
- number of palpitations(at year 3)
- 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)
- left ventricle diameters measured by echocardiography(at year 3)
- number of dyspnea(at year 3)
- number of MACE (Major adverse cardiac events)(at year 3)
- left ventricle volumes measured by echocardiography(at year 3)
- number of thoracic pain(at year 3)
- number of hospital admissions(at year 3)
- left ventricle ejection fraction measured by echocardiography(at year 3)
- aneurism measured by echocardiography(at year 3)
- dyskinesia measured by echocardiography(at year 3)
- sustained ventricular tachycardia on 24h Holter ECG(at year 1)
- evolution of PR interval duration on ECG(at year 1)
- late potentials measured with high amplification ECG(at year 3)
- number of ventricular extrasystoles by stress test(at year 3)
- Left ventricular global longitudinal strain measured by echocardiography(at year 1)
- evolution of QRS width (50mm/s) on ECG(at year 1)
- Number of hospital admissions owing to clinical deterioration(at year 3)
- Evolution of telediastolic right ventricle volume measured by echocardiography(at year 3)
- arrhythmia burden measured by 24h Holter ECG(at year 3)
- Dosage of MMP9 (Matrix metallopeptidase 9)(at year 3)
- Dosage of TIMP2 (Tissue Inhibitory MetalloProtease 2)(at year 3)
- number of ventricular extrasystoles on 24h Holter ECG(at year 1)
- Evolution of functional symptoms by recording adverse events(at year 3)
- Dosage of TIMP1 (Tissue Inhibitory MetalloProtease 1)(at year 3)
- Dosage of IL6 (Interleukin 6)(at year 3)
- Dosage of IL8 (Interleukin 8)(at year 3)
- number of palpitations(at year 1)
- number of ventricular tachycardia(at year 1)
- number of dyspnea(at year 1)
- number of syncope(at year 1)
- number of sudden death(at year 1)
- number of thoracic pain(at year 1)
- number of MACE (Major adverse cardiac events)(at year 1)
- number of hospital admissions(at year 1)
- left ventricle diameters measured by echocardiography(at year 1)
- left ventricle volumes measured by echocardiography(at year 1)
- left ventricle ejection fraction measured by echocardiography(at year 1)
- aneurism measured by echocardiography(at year 1)
- dyskinesia measured by echocardiography(at year 1)
- Dosage of MMP9 (Matrix metallopeptidase 9)(at year 1)
- Dosage of TIMP1 (Tissue Inhibitory MetalloProtease 1)(at year 1)
- Dosage of TIMP2 (Tissue Inhibitory MetalloProtease 2)(at year 1)
- Dosage of IL6 (Interleukin 6)(at year 1)
- Dosage of IL8 (Interleukin 8)(at year 1)