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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by InCor Heart Institute
Sponsor:
Collaborators:
Ministry of Health, Brazil
St Jude Medical Brasil Ltda
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Martino Martinelli Filho, InCor Heart Institute
ClinicalTrials.gov Identifier:
NCT01722942
First received: November 1, 2012
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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 Intervention
Chagas Cardiomyopathy
Non-sustained Ventricular Tachycardia
At Least 10 Points in Rassi Risk Score for Death
Procedure: ICD implantation
Drug: amiodarone hydrochloride

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by InCor Heart Institute:

Primary Outcome Measures:
  • all cause mortality [ Time Frame: three and half years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cardiac mortality [ Time Frame: three and half years ] [ Designated as safety issue: No ]
  • Sudden cardiac death [ Time Frame: three and half years ] [ Designated as safety issue: No ]
  • Worsening heart failure warranting hospitalization [ Time Frame: three and half years ] [ Designated as safety issue: No ]
  • Need for cardiac stimulation in the ICD arm [ Time Frame: three and half years ] [ Designated as safety issue: No ]
  • Need for pacemaker implantation in the amiodarone therapy arm [ Time Frame: three and half years ] [ Designated as safety issue: No ]

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. [ Time Frame: three and half years ] [ Designated as safety issue: No ]

Estimated Enrollment: 1100
Study Start Date: October 2014
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01722942

Contacts
Contact: Martino Martinelli, MD, PhD 55 11 26615515 martino@incor.usp.br
Contact: Sergio F Siqueira, Eng, MsC 55 11 26615514 siqueira@incor.usp.br

Locations
Brazil
Hospital Ana Nery Not yet recruiting
Salvador, BA, Brazil
Contact: Luiz P Magalhães, MD       luizpmagalhaes@uol.com.br   
Contact: Alexandro A Fagundes, MD       alexfagundes@cardiol.br   
Principal Investigator: Luiz P Magalhães, MD         
Sub-Investigator: Alexsandro A Fagundes, MD         
Santa Casa de Salvador Not yet recruiting
Salvador, BA, Brazil
Contact: Ricardo E Pereira, MD       rickeloy@terra.com.br   
Principal Investigator: Ricardo E Pereira, MD         
Hospital Universitário Walter Cantideo Not yet recruiting
Fortaleza, CE, Brazil
Contact: Francisca TM Pereira, MD       tatianap@baydenet.com.br   
Contact: Eduardo A Rocha, MD       eduardoa@cardiol.br   
Principal Investigator: Francisca TM Pereira, MD         
Sub-Investigator: Eduardo A Rocha, MD         
Sub-Investigator: Marcelo P Monteiro, MD         
Hospital de Messejana Not yet recruiting
Fortaleza, CE, Brazil
Contact: João D Souza Neto, MD       jdsneto@cardiol.br   
Contact: Stela MV Sampaio, MD       stelavsampaio@terra.com.br   
Principal Investigator: João D Souza Neto, MD         
Sub-Investigator: Stela MV Sampaio, MD         
Instituto de Cardiologia do Distrito Federal Not yet recruiting
Brasilia, DF, Brazil
Contact: José M Baggio Jr, MD       jmbaggio@cardiol.br   
Principal Investigator: José M Baggio Jr, MD         
Sub-Investigator: Renato Bueno, MD         
Hospital de Base Not yet recruiting
Brasilia, DF, Brazil
Contact: Ayrton K Peres, MD, PhD       ayrton.ritmocardio@gmail.com   
Contact: Tamer N Seixas, MD, PhD       tamersn@cardiol.br   
Principal Investigator: Ayrton K Peres, MD, PhD         
Sub-Investigator: Thamer N Seixas, MD, PhD         
Sub-Investigator: Edna MM Oliveira, MD         
Sub-Investigator: Marcus VN Santos, MD         
Sub-Investigator: Romeu Mello Neto, MD         
Anis Rassi Hospital Not yet recruiting
Goiania, GO, Brazil
Contact: Anis Rassi Jr, MD, PhD       arassijr@terra.com.br   
Principal Investigator: Anis Rassi Jr, MD, PhD         
Hospital das Clínicas de Goiania Not yet recruiting
Goiania, GO, Brazil
Contact: Salvador Rassi, MD, PhD       srassi@cardiol.br   
Principal Investigator: Salvador Rassi, MD, PhD         
Santa Casa de Goiania Not yet recruiting
Goiania, GO, Brazil
Contact: Sérgio Rassi, MD       sgrassi@cultura.com.br   
Contact: Antônio MC Lima, MD       antoniomalanc@gmail.com   
Sub-Investigator: Antonio MC Lima, MD         
Principal Investigator: Sérgio Rassi, MD         
Hospital Felício Rocho Not yet recruiting
Belo Horizonte, MG, Brazil
Contact: Maria CV Moreira, MD, PhD       moreiram@cardiol.br   
Contact: Thiago R Rodrigues, MD       thiagorrodrigues@oi.com.br   
Sub-Investigator: Thiago R Rodrigues, MD         
Principal Investigator: Maria CV Moreira, MD, PhD         
Hospital das Clínicas Samuel Libânio Not yet recruiting
Pouso Alegre, MG, Brazil
Contact: Ricardo A Teixeira, MD, PhD       ricardo.alkmim@hotmail.com   
Principal Investigator: Ricardo A Teixeira, MD, PHD         
Hospital Escola da Universidade Federal do Triângulo Mineiro Not yet recruiting
Uberaba, MG, Brazil
Contact: Celso S Melo, MD       celsosalgado@uol.com.br   
Principal Investigator: Celso S Melo, MD         
Hospital Geral Universitário Not yet recruiting
Cuiabá, MT, Brazil
Contact: Júlio C Oliveira, MD, PhD       juliocesar@atriumcardiologia.com.br   
Principal Investigator: Júlio C Oliveira, MD, PhD         
Hospital Universitário Procape Not yet recruiting
Recife, PE, Brazil
Contact: Dário Sobral Filho, MD, PhD       dsobral@uol.com.br   
Contact: Abelardo G Escarião, MD       escariao@hotmail.com   
Principal Investigator: Dário C Sobral Filho, MD, PhD         
Sub-Investigator: Adelardo G Escariao, MD         
Sub-Investigator: Antonio M Nascimento, MD         
Sub-Investigator: Wilson A Oliveira Jr, MD         
Hospital Santa Casa de Misericórdia de Curitiba Not yet recruiting
Curitiba, PR, Brazil
Contact: Gerson Lemke, MD         
Contact: José CM Jorge, MD, PhD       mourajorge@terra.com.br   
Principal Investigator: Gerson Lemke, MD         
Sub-Investigator: José CM Jorge, MD, PhD         
Hospital Universitário Onofre Lopes - UFRGN Not yet recruiting
Natal, RN, Brazil
Contact: Nestor R Oliveira Neto, MD       nestor_rn@superig.com.br   
Principal Investigator: Nestor R Oliveira Neto, MD         
Hospital do Coração de Natal Not yet recruiting
Natal, RN, Brazil
Contact: Álvaro RB Costa, MD       alvaro@digi.com.br   
Principal Investigator: Álvaro RB Costa, MD         
Hospital e Maternidade Celso Pierro - PUCC Not yet recruiting
Campinas, SP, Brazil
Contact: José MN Lima, MD, PhD       jmarcolima@gmail.com   
Contact: Fernando M Porto, MD       ritmocamp@hotmail.com   
Principal Investigator: José MN Lima, MD, PhD         
Sub-Investigator: Fernando M Porto, MD         
Sub-Investigator: Halim Cury Filho, MD         
Hospital das Clínicas da UNICAMP Not yet recruiting
Campinas, SP, Brazil
Contact: Márcio JO Figueiredo, MD, PhD       mjofig@gmail.com   
Principal Investigator: Márcio JO Figueiredo, MD, PhD         
Sub-Investigator: Otávio R Coelho, MD         
Hospital do Coração da Fundação de Misericórdia de Franca Not yet recruiting
Franca, SP, Brazil
Contact: Rodrigo T Silva, MD, PhD       rotasil@ig.com.br   
Principal Investigator: Rodrigo T Silva, MD, PhD         
HC - FMUSP / Ribeirão Preto Not yet recruiting
Ribeirão Preto, SP, Brazil
Contact: José A Marin-Neto, MD, Full Prof.       marin_neto@yahoo.com   
Contact: Marcelo G Leal, MD, PhD       mgleal@cardiol.br   
Principal Investigator: José A Marin-Neto, MD, FullProf         
Principal Investigator: Marcelo G Leal, MD, PhD         
Sub-Investigator: Elerson Arfelli, MD         
Sub-Investigator: Andre Schmidt, MD, PhD         
Sub-Investigator: Adilson Escorzonic, MD         
Sub-Investigator: Jairo R Silva Jr, MD         
Sub-Investigator: Henrique T Moreira, MD         
Sub-Investigator: Maria LRC Pavao, MD         
Santa Casa de Ribeirão Preto Not yet recruiting
Ribeirão Preto, SP, Brazil, 14080-000
Contact: Antonio Vitor Moraes Jr, MD, PhD    +55 16 97920407    avitor@terra.com.br   
Principal Investigator: Antonio Vitor Moraes Jr, MD, PhD         
Instituto de Moléstias Cardiovasculares Not yet recruiting
São José do Rio Preto, SP, Brazil
Contact: Adalberto Lorga Filho, MD, PhD       lorgafilho@terra.com.br   
Contact: Oswaldo T Greco, MD       oswaldogreco@terra.com.br   
Principal Investigator: Adalberto Lorga Filho, MD, PhD         
Sub-Investigator: Rinaldo Santos, MD         
Instituto Dante Pazzanese de Cardiologia Not yet recruiting
São Paulo, SP, Brazil
Contact: Juan C Pachón, MD       juanpachon@gmail.com   
Principal Investigator: Juan C Pachon, MD         
Escola Paulista de Medicina Not yet recruiting
São Paulo, SP, Brazil
Contact: Angelo Paola, MD, Full Prof       depaola@uol.com.br   
Contact: Guilherme Fenelon, MD, PhD       guilhermefenelon@uol.com.br   
Principal Investigator: Angelo Paola, MD, Full Prof         
Sub-Investigator: Guilherme Fenelon, MD, PhD         
Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Not yet recruiting
São Paulo, SP, Brazil, 05403000
Contact: Martino Martinelli, MD, PhD    55 11 26615515    martino@incor.usp.br   
Contact: Sergio F Siqueira, Eng, MsC    55 11 26615514    siqueira@incor.usp.br   
Sub-Investigator: Sérgio F Siqueira, Eng, MsC         
Sub-Investigator: Giselle L Peixoto, MD         
Sub-Investigator: Roberto Costa, MD, PhD         
Sub-Investigator: Maurício I Scanavacca, MD, PhD         
Sub-Investigator: Antonio CP Barreto, MD, PhD         
Sub-Investigator: Barbara M Ianni, MD, PhD         
Sub-Investigator: Denise T Hachul, MD, PhD         
Sub-Investigator: Edmar Bocchi, MD, PhD         
Sub-Investigator: Fernando Bacal, MD, PhD         
Sub-Investigator: Francisco CC Darriex, MD, PhD         
Sub-Investigator: Germano Souza, MD, PhD         
Sub-Investigator: Silvana AD Nishioka, MD, PhD         
Sub-Investigator: Anisio AA Pedrosa, MD, PhD         
Sub-Investigator: Ricardo A Teixeira, MD, PhD         
Principal Investigator: Jose Antonio Marin-Neto, Prof         
Principal Investigator: Anis Rassi Jr, MD, PhD         
Beneficiência Portuguesa Not yet recruiting
São Paulo, SP, Brazil
Contact: Silas S Galvão Filho, MD       sdsantos@uol.com.br   
Contact: José TM Vasconcelos, MD, PhD       tarr@terra.com.br   
Principal Investigator: Silas S Galvão Filho         
Sub-Investigator: José TM Vasconcelos, MD, PhD         
Sponsors and Collaborators
InCor Heart Institute
Ministry of Health, Brazil
St Jude Medical Brasil Ltda
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Martino Martinelli, Prof. InCor Heart Institute
  More Information

No publications provided by InCor Heart Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Martino Martinelli Filho, PhD, MD, InCor Heart Institute
ClinicalTrials.gov Identifier: NCT01722942     History of Changes
Other Study ID Numbers: CHAGASICS
Study First Received: November 1, 2012
Last Updated: September 8, 2014
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by InCor Heart Institute:
Chagas cardiomyopathy
sudden cardiac death
primary prevention of death
amiodarone
implantable cardioverter defibrillator

Additional relevant MeSH terms:
Chagas Disease
Death
Tachycardia
Cardiomyopathies
Tachycardia, Ventricular
Chagas Cardiomyopathy
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Trypanosomiasis
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Amiodarone
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on September 16, 2014