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

Chagas Cardiomyopathy Clinical Trial

— CHAGASICS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01722942
• Other study ID #: CHAGASICS
• Status: Recruiting
• Phase: N/A
• Start date: October 6, 2014
• Est. completion date: July 31, 2022

Study information

• Verified date: August 2021
• Source: InCor Heart Institute
• Contact: Martino Martinelli, MD, PhD
• Phone: 55 11 26615515
• Email: martino[@]incor.usp.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• At Least 10 Points in Rassi Risk Score for Death
• Cardiomyopathies
• Chagas Cardiomyopathy
• Death
• Non-sustained Ventricular Tachycardia
• Tachycardia
• Tachycardia, Ventricular

Intervention

Procedure:
• ICD implantation
ventricular ICD implantation

Drug:
• amiodarone hydrochloride
amiodarone prescription

Locations

Country	Name	City	State
Brazil	Hospital Felício Rocho	Belo Horizonte	MG
Brazil	Instituto de Cardiologia do Distrito Federal	Brasilia	DF
Brazil	Hospital das Clínicas da UNICAMP	Campinas	SP
Brazil	Hospital Geral Universitário	Cuiabá	Mount
Brazil	Hospital Santa Casa de Misericórdia de Curitiba	Curitiba	PR
Brazil	Hospital Universitário Walter Cantideo	Fortaleza	CE
Brazil	Anis Rassi Hospital	Goiania	GO
Brazil	Hospital das Clínicas de Goiania	Goiania	GO
Brazil	Santa Casa de Goiania	Goiania	GO
Brazil	Hospital das Clínicas Samuel Libânio	Pouso Alegre	MG
Brazil	Hospital Universitário Procape	Recife	PE
Brazil	HC - FMUSP / Ribeirão Preto	Ribeirão Preto	SP
Brazil	Santa Casa de Ribeirão Preto	Ribeirão Preto	SP
Brazil	Hospital Ana Nery	Salvador	BA
Brazil	Instituto de Moléstias Cardiovasculares	São José do Rio Preto	SP
Brazil	Beneficiência Portuguesa	São Paulo	SP
Brazil	Escola Paulista de Medicina	São Paulo	SP
Brazil	Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo	SP
Brazil	Instituto Dante Pazzanese de Cardiologia	São Paulo	SP
Brazil	Hospital Escola da Universidade Federal do Triângulo Mineiro	Uberaba	MG

Sponsors (3)

Lead Sponsor	Collaborator
InCor Heart Institute	Abbott Medical Devices, Ministry of Health, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Subgroup analyses will include gender, age = or < 60 years, occurrence or not of atrial	three and half years
Primary	all cause mortality	All cause mortality	three and half years
Secondary	Cardiac mortality	cardiac mortality	three and half years
Secondary	Sudden cardiac death	Sudden cardiac death	three and half years
Secondary	Worsening heart failure warranting hospitalization	Worsening heart failure warranting hospitalization	three and half years
Secondary	Need for cardiac stimulation in the ICD arm	Need for cardiac stimulation in the ICD arm	three and half years
Secondary	Need for pacemaker implantation in the amiodarone therapy arm	Need for pacemaker implantation in the amiodarone therapy arm	three and half years