Clinical trial NCT01722942: Amiodarone Against ICD Therapy in Chagas Cardiomyopathy for Primary Prevention of Death
Official title: CHronic Use of Amiodarone aGAinSt Implantable Cardioverter-defibrillator Therapy for Primary Prevention of Death in Patients With Chagas Cardiomyopathy Study (CHAGASICS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chagas Cardiomyopathy
Non-sustained Ventricular Tachycardia
At Least 10 Points in Rassi Risk Score for Death
Keywords: Chagas cardiomyopathy
sudden cardiac death
primary prevention of death
amiodarone
implantable cardioverter defibrillator
Lead sponsor: InCor Heart Institute
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
name: Abbott Medical Devices
First posted: 2012-11-07
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: all cause mortality
timeFrame: three and half years
Secondary outcomes:
measure: Cardiac mortality
timeFrame: three and half years
measure: Sudden cardiac death
timeFrame: three and half years
measure: Worsening heart failure warranting hospitalization
timeFrame: three and half years
measure: Need for cardiac stimulation in the ICD arm
timeFrame: three and half years
measure: Need for pacemaker implantation in the amiodarone therapy arm
timeFrame: three and half years
Other outcomes:
measure: 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.
timeFrame: three and half years
Locations:
city: Salvador
country: Brazil
facility: Hospital Ana Nery
state: BA
city: Fortaleza
country: Brazil
facility: Hospital Universitário Walter Cantideo
state: CE
city: Brasilia
country: Brazil
facility: Instituto de Cardiologia do Distrito Federal
state: DF
city: Goiania
country: Brazil
facility: Anis Rassi Hospital
state: GO
city: Goiania
country: Brazil
facility: Hospital das Clínicas de Goiania
state: GO
city: Goiania
country: Brazil
facility: Santa Casa de Goiania
state: GO
city: Belo Horizonte
country: Brazil
facility: Hospital Felício Rocho
state: MG
city: Pouso Alegre
country: Brazil
facility: Hospital das Clínicas Samuel Libânio
state: MG
city: Uberaba
country: Brazil
facility: Hospital Escola da Universidade Federal do Triângulo Mineiro
state: MG
city: Cuiabá
country: Brazil
facility: Hospital Geral Universitário
state: Mount
city: Recife
country: Brazil
facility: Hospital Universitário Procape
state: PE
city: Curitiba
country: Brazil
facility: Hospital Santa Casa de Misericórdia de Curitiba
state: PR
city: Campinas
country: Brazil
facility: Hospital das Clínicas da UNICAMP
state: SP
city: Ribeirão Preto
country: Brazil
facility: Santa Casa de Ribeirão Preto
state: SP
city: Ribeirão Preto
country: Brazil
facility: HC - FMUSP / Ribeirão Preto
state: SP
city: São José do Rio Preto
country: Brazil
facility: Instituto de Moléstias Cardiovasculares
state: SP
city: São Paulo
country: Brazil
facility: Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
state: SP
city: São Paulo
country: Brazil
facility: Beneficiência Portuguesa
state: SP
city: São Paulo
country: Brazil
facility: Escola Paulista de Medicina
state: SP
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
state: SP
Study officials:
affiliation: InCor Heart Institute
name: Martino Martinelli, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martinelli M, Rassi A Jr, Marin-Neto JA, de Paola AA, Berwanger O, Scanavacca MI, Kalil R, de Siqueira SF. CHronic use of Amiodarone aGAinSt Implantable cardioverter-defibrillator therapy for primary prevention of death in patients with Chagas cardiomyopathy Study: rationale and design of a randomized clinical trial. Am Heart J. 2013 Dec;166(6):976-982.e4. doi: 10.1016/j.ahj.2013.08.027. Epub 2013 Oct 11.