Chagas CardiomyopathyCHAGASICSNCT01722942
Amiodarone Against ICD Therapy in Chagas Cardiomyopathy for Primary Prevention of Death
A study testing ICD implantation and amiodarone hydrochloride in people with Chagas Cardiomyopathy and Non-sustained Ventricular Tachycardia, run by InCor Heart Institute at 20 sites in Brazil.
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chagas Cardiomyopathy, Non-sustained Ventricular Tachycardia, At Least 10 Points in Rassi Risk Score for Death
- What is being tested?
- ICD implantation and amiodarone hydrochloride
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,100 participants
- Where
- 20 sitesBrazil
- Study dates
- 6 Oct 2014to 31 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 18Show fewer
- 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.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Brazil20 sites, 20 recruiting
- Not yet recruiting
Hospital Felício Rocho
Belo Horizonte, Minas Gerais
Maria CV Moreira, MD, PhD, moreiram@cardiol.br
Thiago R Rodrigues, MD, thiagorrodrigues@oi.com.br
- Recruiting
Instituto de Cardiologia do Distrito Federal
Brasília, Federal District
José M Baggio Jr, MD, jmbaggio@cardiol.br
José M Baggio Jr, MD
- Not yet recruiting
Hospital das Clínicas da UNICAMP
Campinas, São Paulo
Márcio JO Figueiredo, MD, PhD, mjofig@gmail.com
Márcio JO Figueiredo, MD, PhD
- Not yet recruiting
Hospital Geral Universitário
Cuiabá, Mount
Júlio C Oliveira, MD, PhD, juliocesar@atriumcardiologia.com.br
Júlio C Oliveira, MD, PhD
- Not yet recruiting
Hospital Santa Casa de Misericórdia de Curitiba
Curitiba, Paraná
Gerson Lemke, MD
José CM Jorge, MD, PhD, mourajorge@terra.com.br
- Recruiting
Hospital Universitário Walter Cantideo
Fortaleza, Ceará
Francisca TM Pereira, MD, tatianap@baydenet.com.br
Eduardo A Rocha, MD, eduardoa@cardiol.br
- Not yet recruiting
Anis Rassi Hospital
Goiânia, Goiás
Anis Rassi Jr, MD, PhD, arassijr@terra.com.br
Anis Rassi Jr, MD, PhD
- Recruiting
Hospital das Clínicas de Goiania
Goiânia, Goiás
Salvador Rassi, MD, PhD, srassi@cardiol.br
Salvador Rassi, MD, PhD
- Not yet recruiting
Santa Casa de Goiania
Goiânia, Goiás
Sérgio Rassi, MD, sgrassi@cultura.com.br
Antônio MC Lima, MD, antoniomalanc@gmail.com
- Not yet recruiting
Hospital das Clínicas Samuel Libânio
Pouso Alegre, Minas Gerais
Ricardo A Teixeira, MD, PhD, ricardo.alkmim@hotmail.com
Ricardo A Teixeira, MD, PHD
- Not yet recruiting
Hospital Universitário Procape
Recife, Pernambuco
Dário Sobral Filho, MD, PhD, dsobral@uol.com.br
Abelardo G Escarião, MD, escariao@hotmail.com
- Not yet recruiting
Santa Casa de Ribeirão Preto
Ribeirão Preto, São Paulo, 14080-000
Antonio Vitor Moraes Jr, MD, PhD, +55 16 97920407, avitor@terra.com.br
Antonio Vitor Moraes Jr, MD, PhD
- Recruiting
HC - FMUSP / Ribeirão Preto
Ribeirão Preto, São Paulo
José A Marin-Neto, MD, FullProf, marin_neto@yahoo.com
Marcelo G Leal, MD, PhD, mgleal@cardiol.br
- Not yet recruiting
Hospital Ana Nery
Salvador, Estado de Bahia
Luiz P Magalhães, MD, luizpmagalhaes@uol.com.br
Alexandro A Fagundes, MD, alexfagundes@cardiol.br
- Recruiting
Instituto de Moléstias Cardiovasculares
São José do Rio Preto, São Paulo
Adalberto Lorga Filho, MD, PhD, lorgafilho@terra.com.br
Oswaldo T Greco, MD, oswaldogreco@terra.com.br
- Recruiting
Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, São Paulo, 05403000
Martino Martinelli, MD, PhD, 55 11 26615515, martino@incor.usp.br
Sergio F Siqueira, Eng, MsC, 55 11 26615514, siqueira@incor.usp.br
- Not yet recruiting
Beneficiência Portuguesa
São Paulo, São Paulo
Silas S Galvão Filho, MD, sdsantos@uol.com.br
José TM Vasconcelos, MD, PhD, tarr@terra.com.br
- Recruiting
Escola Paulista de Medicina
São Paulo, São Paulo
Angelo Paola, MD, FullProf, depaola@uol.com.br
Guilherme Fenelon, MD, PhD, guilhermefenelon@uol.com.br
- Recruiting
Instituto Dante Pazzanese de Cardiologia
São Paulo, São Paulo
Paulo TJ Medeiros, MD, +5511996462424, paulo.medeiros@dantepazzanese.org.br
Paulo TJ Medeiros, MD
- Not yet recruiting
Hospital Escola da Universidade Federal do Triângulo Mineiro
Uberaba, Minas Gerais
Celso S Melo, MD, celsosalgado@uol.com.br
Celso S Melo, MD
About this study
Official title: 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).
Read the 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.
- Conditions
- Chagas Cardiomyopathy, Non-sustained Ventricular Tachycardia, At Least 10 Points in Rassi Risk Score for Death
- Being tested
- ICD implantation, amiodarone hydrochloride
- Keywords
- Chagas cardiomyopathy, sudden cardiac death, primary prevention of death, amiodarone, implantable cardioverter defibrillator
- Medical subject headings
- Chagas Cardiomyopathy, Death, Sudden, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICD implantationProcedure or surgery
Also called ICD
ventricular ICD implantation
amiodarone hydrochlorideDrug
Also called amiodarone
amiodarone prescription
| Study group | Role | What they receive |
|---|---|---|
| ICD group | Active comparator | 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. Receives: Procedure: ICD implantation |
| Amiodarone Group | Active comparator | 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. Receives: Drug: amiodarone hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
all cause mortality
All cause mortality
Measured: three and half years
Secondary outcomes (5)
Cardiac mortality
cardiac mortality
Measured: three and half years
Sudden cardiac death
Sudden cardiac death
Measured: three and half years
Worsening heart failure warranting hospitalization
Worsening heart failure warranting hospitalization
Measured: three and half years
Need for cardiac stimulation in the ICD arm
Need for cardiac stimulation in the ICD arm
Measured: three and half years
Need for pacemaker implantation in the amiodarone therapy arm
Need for pacemaker implantation in the amiodarone therapy arm
Measured: three and half years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study start6 Oct 2014
- Primary completion31 Jul 2022 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chagas CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InCor Heart Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Brazil, Abbott Medical Devices
- Responsible party
- Principal investigator, Martino Martinelli Filho, InCor Heart Institute
- Investigators
- Martino Martinelli, Prof., Principal investigator, InCor Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01722942
- Sponsor's protocol ID
- CHAGASICS
- Acronym
- CHAGASICS
- Status last verified
- Aug 2021
- First submitted
- 1 Nov 2012
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Martinelli-Filho M, Marin-Neto JA, Scanavacca MI, de Paola AAV, Medeiros PTJ, Owen R, Pocock SJ, de Siqueira SF; CHAGASICS investigators. Amiodarone or Implantable Cardioverter-Defibrillator in Chagas Cardiomyopathy: The CHAGASICS Randomized Clinical Trial. JAMA Cardiol. 2024 Dec 1;9(12):1073-1081. doi: 10.1001/jamacardio.2024.3169.
PubMed 39356542Martinelli 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.
PubMed 24268211
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CHronic Use of Amiodarone aGAinSt Implantable Cardioverter-defibrillator Therapy for Primary Prevention of Death in Patients With Chagas Cardiomyopathy Study (CHAGASICS)
- ClinicalTrials.gov ID
- NCT01722942
- Acronym / sponsor ID
- CHAGASICS / CHAGASICS
- 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
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,100 participants (estimated)
- Lead sponsor
- InCor Heart InstituteUniversity, hospital or other
- Collaborators
- Ministry of Health, Brazil, Abbott Medical Devices
- Study start
- 6 Oct 2014 (actual)
- Primary completion
- 31 Jul 2022 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 7 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICD group | Active comparator | Procedure: ICD implantationICD 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. |
| Amiodarone Group | Active comparator | Drug: amiodarone hydrochloridePatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ICD implantationAlso: ICDventricular ICD implantation | Procedure or surgery | ICD group |
| amiodarone hydrochlorideAlso: amiodaroneamiodarone prescription | Drug | Amiodarone Group |
Primary outcome
all cause mortality
Time frame: three and half years
All cause mortality
5 secondary outcomes
Cardiac mortality
Time frame: three and half years
Sudden cardiac death
Time frame: three and half years
Worsening heart failure warranting hospitalization
Time frame: three and half years
Need for cardiac stimulation in the ICD arm
Time frame: three and half years
Need for pacemaker implantation in the amiodarone therapy arm
Time frame: three and half years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2021.
- Derived from this study: PubMed 39356542Martinelli-Filho M, Marin-Neto JA, Scanavacca MI, de Paola AAV, Medeiros PTJ, Owen R, Pocock SJ, de Siqueira SF; CHAGASICS investigators. Amiodarone or Implantable Cardioverter-Defibrillator in Chagas Cardiomyopathy: The CHAGASICS Randomized Clinical Trial. JAMA Cardiol. 2024 Dec 1;9(12):1073-1081. doi: 10.1001/jamacardio.2024.3169.
- Derived from this study: PubMed 24268211Martinelli 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.
Related trials for Chagas Cardiomyopathy
Recruiting
Cardiac Contractility Modulation in Chagas Heart Disease
Chagas Cardiomyopathy, Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martino Martinelli, Prof. principal investigator
InCor Heart Institute
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ICD implantation and amiodarone hydrochloride in people with Chagas Cardiomyopathy and Non-sustained Ventricular Tachycardia, run by InCor Heart Institute at 20 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martino Martinelli, MD, PhD (55 11 26615515, martino@incor.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
all cause mortality (time frame: three and half years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01722942, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2021.