CHronic Use of Amiodarone aGAinSt Implantable Cardioverter-defibrillator Therapy for Primary Prevention of Death in Patients With Chagas Cardiomyopathy Study (CHAGASICS)
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 1,100
- 试验地点
- 20
- 主要终点
- all cause mortality
研究概览
简要总结
The primary objective is to compare the efficacy of the treatment using implantable cardioverter defibrillator (ICD) implantation to that of the treatment using amiodarone in the primary prevention of all-cause mortality in high-risk patients with Chagas cardiomyopathy and non-sustained ventricular tachycardia (NSVT).
详细描述
Chagas disease is an endemic problem in Latin America, where millions of people are chronically infected by Trypanosoma cruzi. The disease has also recently become clinically and epidemiologically relevant in several other countries due to social factors related to individuals migration and globalization. Chagas cardiomyopathy occurs in 30%-50% of the infected individuals, leading to considerable morbidity and mortality rates. Sudden cardiac death is the major cause of death in patients with Chagas cardiomyopathy. While implantable cardioverter defibrillator and treatment with amiodarone have been recommended and performed empirically for the secondary prevention in patients with Chagas cardiomyopathy, no consistent scientific evidence exists on the role of these therapeutic strategies for the primary prevention of Sudden cardiac death in patients with Chagas cardiomyopathy and high mortality risk.
The main hypothesis of this study is that implantable cardioverter defibrillator implantation is more efficient in the primary prevention of death in Chagas cardiomyopathy than drug therapy with amiodarone in patients with documented non-sustained ventricular tachycardia.
We should point out that the death risk will be assessed using the Rassi risk score for death prediction validated based on non-invasive variables and, depending on the results of this study, it may guide the indication of implantable cardioverter defibrillator in Chagas cardiomyopathy.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent prior to randomization and any study procedure;
- •Both genders, age > 18 years and < 75 years;
- •Recent (previous 6 months) documented positive serologic test for Chagas disease in at least two different tests (indirect hemagglutination, indirect immunofluorescence, or ELISA);
- •Presence of at least 10 points in Rassi risk score for death prediction;
- •Presence of at least 1 episode of NSVT on Holter monitoring, defined as > 3 successive beats and duration < 30 seconds, with HR > 120 bpm is mandatory.
排除标准
- •Participation in another study currently or < 1 year ago, except for totally unrelated observational studies;
- •Other concomitant cardiovascular disease, including uncontrolled diabetes mellitus (systemic hypertension without target-organ impairment is allowed);
- •Renal dysfunction (serum creatinine > 1.5 mg/dL or glomerular filtration rate (GFR) < 60 mL/min/1.73m2) or liver dysfunction with diagnosis of cirrhosis or portal hypertension or elevated serum enzymes (AST or ALT) > 3 x the upper normal limit;
- •Moderate or severe chronic obstructive pulmonary disease;
- •Peripheral polyneuropathy;
- •Hypo or hyper-thyroidism;
- •Current alcoholism or quit for <2 years;
- •Mental disorder or illicit drug addiction;
- •Life expectancy < 1 year, because of the disease itself or of comorbidities (including NYHA class IV CHF);
- •Pregnancy or breastfeeding;
- •Childbearing potential during the study (non-menopausal patients who have not undergone a safe and permanent birth control method);
- •Other contraindications for the use of amiodarone: previous intolerance to the drug; HR < 55bpm; sinus node disease; type II Mobitz; fixed 2:1 AV block; advanced degree atrioventricular block (AV) block; Complete AV block; QTc > 500mseg;
- •Formal indication for the use of amiodarone or defibrillator (NSVT and very disturbing palpitations, presyncope or syncope; SVT; recovery from cardiac arrest);
- •Use of amiodarone in the past 6 months, except if started for < 2 weeks and if loading dose had been <10g and maintenance dose ≤100mg/day;
- •Current use of betablocker considered clinically indispensable, with bradycardia < 55/min or AV block ≥ 1st degree, without pacemaker implantation;
- •Current use of other medications with contraindication to the concomitant use of amiodarone;
- •Persistent or permanent atrial fibrillation;
- •Previous withdrawal from this study.
研究组 & 干预措施
ICD group
ICD implantation will be performed according to the Institution protocol of each participating center; single-chamber devices are preferred and programming should prioritize the patient's own pace, avoiding ventricular stimulation.
干预措施: ICD implantation (Procedure)
Amiodarone Group
Patients randomized for this group will receive amiodarone hydrochloride (once a day) according to the following regimen:
- Initial oral loading dose of 600 mg/day for 10 days on an outpatient basis;
- After the loading period, an oral dose between 200 and 400 mg/day should be maintained until study termination. The determination of the optimal maintenance dose will be left at the discretion of each investigator; this dose may be based on the therapeutic response on 24-hour Holter monitoring, resting heart rate (HR), side effects, prolonged corrected QT interval (QTc), etc. Dose adjustments will be allowed throughout the study period provided the maintenance dose is kept between 200 and 400 mg/day. If the patient cannot tolerate the minimum 200 mg/day dose, amiodarone should be discontinued permanently and treatment should be considered interrupted.
干预措施: amiodarone hydrochloride (Drug)
结局指标
主要结局
all cause mortality
时间窗: three and half years
All cause mortality
次要结局
- Worsening heart failure warranting hospitalization(three and half years)
- Cardiac mortality(three and half years)
- Sudden cardiac death(three and half years)
- Need for cardiac stimulation in the ICD arm(three and half years)
- Need for pacemaker implantation in the amiodarone therapy arm(three and half years)
研究者
Martino Martinelli Filho
PhD, MD
InCor Heart Institute