CHAGASICS: Amiodarone Against ICD Therapy in Chagas Cardiomyopathy for Primary Prevention of Death

Sponsor

InCor Heart Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT01722942

Collaborator

Ministry of Health, Brazil (Other), Abbott Medical Devices (Industry)

1,100

Enrollment

Locations

Arms

93.8

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Chagas Cardiomyopathy Non-sustained Ventricular Tachycardia At Least 10 Points in Rassi Risk Score for Death	Procedure: ICD implantation Drug: amiodarone hydrochloride	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CHronic Use of Amiodarone aGAinSt Implantable Cardioverter-defibrillator Therapy for Primary Prevention of Death in Patients With Chagas Cardiomyopathy Study (CHAGASICS)

Actual Study Start Date :

Oct 6, 2014

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Procedure: ICD implantation ventricular ICD implantation Other Names: ICD
Active Comparator: 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.	Drug: amiodarone hydrochloride amiodarone prescription Other Names: amiodarone

Arm

Intervention/Treatment

Active Comparator: 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.

Procedure: ICD implantation

ventricular ICD implantation

Other Names:

ICD

Active Comparator: 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.

Drug: amiodarone hydrochloride

amiodarone prescription

Other Names:

amiodarone

Outcome Measures

Primary Outcome Measures

all cause mortality [three and half years]
All cause mortality

Secondary Outcome Measures

Cardiac mortality [three and half years]
cardiac mortality
Sudden cardiac death [three and half years]
Sudden cardiac death
Worsening heart failure warranting hospitalization [three and half years]
Worsening heart failure warranting hospitalization
Need for cardiac stimulation in the ICD arm [three and half years]
Need for cardiac stimulation in the ICD arm
Need for pacemaker implantation in the amiodarone therapy arm [three and half years]
Need for pacemaker implantation in the amiodarone therapy arm

Other Outcome Measures

Subgroup analyses will include gender, age ≥ or < 60 years, occurrence or not of atrial fibrillation, New York Heart Association (NYHA) functional class I and II versus III and IV, as well as Rassi score points. [three and half years]
Subgroup analyses will include gender, age ≥ or < 60 years, occurrence or not of atrial

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Ana Nery	Salvador	BA	Brazil
2	Hospital Universitário Walter Cantideo	Fortaleza	CE	Brazil
3	Instituto de Cardiologia do Distrito Federal	Brasilia	DF	Brazil
4	Anis Rassi Hospital	Goiania	GO	Brazil
5	Hospital das Clínicas de Goiania	Goiania	GO	Brazil
6	Santa Casa de Goiania	Goiania	GO	Brazil
7	Hospital Felício Rocho	Belo Horizonte	MG	Brazil
8	Hospital das Clínicas Samuel Libânio	Pouso Alegre	MG	Brazil
9	Hospital Escola da Universidade Federal do Triângulo Mineiro	Uberaba	MG	Brazil
10	Hospital Geral Universitário	Cuiabá	Mount	Brazil
11	Hospital Universitário Procape	Recife	PE	Brazil
12	Hospital Santa Casa de Misericórdia de Curitiba	Curitiba	PR	Brazil
13	Hospital das Clínicas da UNICAMP	Campinas	SP	Brazil
14	Santa Casa de Ribeirão Preto	Ribeirão Preto	SP	Brazil	14080-000
15	HC - FMUSP / Ribeirão Preto	Ribeirão Preto	SP	Brazil
16	Instituto de Moléstias Cardiovasculares	São José do Rio Preto	SP	Brazil
17	Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo	SP	Brazil	05403000
18	Beneficiência Portuguesa	São Paulo	SP	Brazil
19	Escola Paulista de Medicina	São Paulo	SP	Brazil
20	Instituto Dante Pazzanese de Cardiologia	São Paulo	SP	Brazil