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

August 24, 2021 updated by: Martino Martinelli Filho, InCor Heart Institute

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

1100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
    • BA
      • Salvador, BA, Brazil
        • Not yet recruiting
        • Hospital Ana Nery
        • Contact:
        • Contact:
        • Principal Investigator:
          • Luiz P Magalhães, MD
        • Sub-Investigator:
          • Alexsandro A Fagundes, MD
    • CE
      • Fortaleza, CE, Brazil
        • Recruiting
        • Hospital Universitário Walter Cantideo
        • Contact:
        • Contact:
        • Principal Investigator:
          • Francisca TM Pereira, MD
        • Sub-Investigator:
          • Eduardo A Rocha, MD
        • Sub-Investigator:
          • Marcelo P Monteiro, MD
    • DF
      • Brasilia, DF, Brazil
        • Recruiting
        • Instituto de Cardiologia do Distrito Federal
        • Contact:
        • Principal Investigator:
          • José M Baggio Jr, MD
        • Sub-Investigator:
          • Renato Bueno, MD
    • GO
      • Goiania, GO, Brazil
        • Not yet recruiting
        • Anis Rassi Hospital
        • Contact:
        • Principal Investigator:
          • Anis Rassi Jr, MD, PhD
      • Goiania, GO, Brazil
        • Recruiting
        • Hospital das Clínicas de Goiânia
        • Contact:
        • Principal Investigator:
          • Salvador Rassi, MD, PhD
      • Goiania, GO, Brazil
        • Not yet recruiting
        • Santa Casa de Goiania
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Antonio MC Lima, MD
        • Principal Investigator:
          • Sérgio Rassi, MD
    • MG
      • Belo Horizonte, MG, Brazil
        • Not yet recruiting
        • Hospital Felicio Rocho
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Thiago R Rodrigues, MD
        • Principal Investigator:
          • Maria CV Moreira, MD, PhD
      • Pouso Alegre, MG, Brazil
        • Not yet recruiting
        • Hospital das Clinicas Samuel Libanio
        • Contact:
        • Principal Investigator:
          • Ricardo A Teixeira, MD, PHD
      • Uberaba, MG, Brazil
        • Not yet recruiting
        • Hospital Escola da Universidade Federal do Triângulo Mineiro
        • Contact:
        • Principal Investigator:
          • Celso S Melo, MD
    • Mount
      • Cuiabá, Mount, Brazil
        • Not yet recruiting
        • Hospital Geral Universitário
        • Contact:
        • Principal Investigator:
          • Júlio C Oliveira, MD, PhD
    • PE
      • Recife, PE, Brazil
        • Not yet recruiting
        • Hospital Universitário Procape
        • Contact:
        • Contact:
        • 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
    • PR
      • Curitiba, PR, Brazil
        • Not yet recruiting
        • Hospital Santa Casa de Misericórdia de Curitiba
        • Contact:
          • Gerson Lemke, MD
        • Contact:
        • Principal Investigator:
          • Gerson Lemke, MD
        • Sub-Investigator:
          • José CM Jorge, MD, PhD
    • SP
      • Campinas, SP, Brazil
        • Not yet recruiting
        • Hospital das Clínicas da UNICAMP
        • Contact:
        • Principal Investigator:
          • Márcio JO Figueiredo, MD, PhD
        • Sub-Investigator:
          • Otávio R Coelho, MD
      • Ribeirão Preto, SP, Brazil, 14080-000
        • Not yet recruiting
        • Santa Casa de Ribeirão Preto
        • Contact:
        • Principal Investigator:
          • Antonio Vitor Moraes Jr, MD, PhD
      • Ribeirão Preto, SP, Brazil
        • Recruiting
        • HC - FMUSP / Ribeirão Preto
        • Contact:
        • Contact:
        • 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 LC Pavao, MD
      • São José do Rio Preto, SP, Brazil
        • Recruiting
        • Instituto de Molestias Cardiovasculares
        • Contact:
        • Contact:
        • Principal Investigator:
          • Adalberto Lorga Filho, MD, PhD
        • Sub-Investigator:
          • Rinaldo Santos, MD
      • São Paulo, SP, Brazil, 05403000
        • Recruiting
        • Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Sérgio F Siqueira, Eng, MsC
        • Sub-Investigator:
          • Giselle L Peixoto, MD
        • Sub-Investigator:
          • Roberto Costa, MD, PhD
        • Sub-Investigator:
          • Edmar Bocchi, MD, PhD
        • Sub-Investigator:
          • Fernando Bacal, MD, PhD
        • Sub-Investigator:
          • Francisco CC Darriex, 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
      • São Paulo, SP, Brazil
        • Not yet recruiting
        • Beneficiência Portuguesa
        • Contact:
        • Contact:
        • Principal Investigator:
          • Silas S Galvão Filho
        • Sub-Investigator:
          • José TM Vasconcelos, MD, PhD
      • São Paulo, SP, Brazil
        • Recruiting
        • Escola Paulista de Medicina
        • Contact:
        • Contact:
        • Principal Investigator:
          • Angelo Paola, MD, FullProf
        • Sub-Investigator:
          • Guilherme Fenelon, MD, PhD
      • São Paulo, SP, Brazil
        • Recruiting
        • Instituto Dante Pazzanese de Cardiologia
        • Contact:
        • Principal Investigator:
          • Paulo TJ Medeiros, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
all cause mortality
Time Frame: three and half years
All cause mortality
three and half years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac mortality
Time Frame: three and half years
cardiac mortality
three and half years
Sudden cardiac death
Time Frame: three and half years
Sudden cardiac death
three and half years
Worsening heart failure warranting hospitalization
Time Frame: three and half years
Worsening heart failure warranting hospitalization
three and half years
Need for cardiac stimulation in the ICD arm
Time Frame: 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
Time Frame: three and half years
Need for pacemaker implantation in the amiodarone therapy arm
three and half years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Subgroup analyses will include gender, age ≥ or < 60 years, occurrence or not of atrial
three and half years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

InCor Heart Institute

Collaborators

Ministry of Health, Brazil
Abbott Medical Devices

Investigators

  • Principal Investigator: Martino Martinelli, Prof., InCor Heart Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 6, 2014

Primary Completion (ANTICIPATED)

July 31, 2022

Study Completion (ANTICIPATED)

July 31, 2022

Study Registration Dates

First Submitted

November 1, 2012

First Submitted That Met QC Criteria

November 5, 2012

First Posted (ESTIMATE)

November 7, 2012

Study Record Updates

Last Update Posted (ACTUAL)

August 30, 2021

Last Update Submitted That Met QC Criteria

August 24, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHAGASICS

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chagas Cardiomyopathy

Clinical Trials on ICD implantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe