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

NCT ID: NCT01722942

Last Updated: 2021-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

1100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-06

Study Completion Date

2022-07-31

Brief Summary

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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

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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

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

ICD implantation

Intervention Type PROCEDURE

ventricular ICD implantation

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.

Group Type ACTIVE_COMPARATOR

amiodarone hydrochloride

Intervention Type DRUG

amiodarone prescription

Interventions

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ICD implantation

ventricular ICD implantation

Intervention Type PROCEDURE

amiodarone hydrochloride

amiodarone prescription

Intervention Type DRUG

Other Intervention Names

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ICD amiodarone

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, Brazil

OTHER_GOV

Sponsor Role collaborator

Abbott Medical Devices

INDUSTRY

Sponsor Role collaborator

InCor Heart Institute

OTHER

Sponsor Role lead

Responsible Party

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Martino Martinelli Filho

PhD, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martino Martinelli, Prof.

Role: PRINCIPAL_INVESTIGATOR

InCor Heart Institute

Locations

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Hospital Universitário Walter Cantideo

Fortaleza, Ceará, Brazil

Site Status RECRUITING

Hospital Ana Nery

Salvador, Estado de Bahia, Brazil

Site Status NOT_YET_RECRUITING

Instituto de Cardiologia do Distrito Federal

Brasília, Federal District, Brazil

Site Status RECRUITING

Anis Rassi Hospital

Goiânia, Goiás, Brazil

Site Status NOT_YET_RECRUITING

Hospital das Clínicas de Goiania

Goiânia, Goiás, Brazil

Site Status RECRUITING

Santa Casa de Goiania

Goiânia, Goiás, Brazil

Site Status NOT_YET_RECRUITING

Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

Site Status NOT_YET_RECRUITING

Hospital das Clínicas Samuel Libânio

Pouso Alegre, Minas Gerais, Brazil

Site Status NOT_YET_RECRUITING

Hospital Escola da Universidade Federal do Triângulo Mineiro

Uberaba, Minas Gerais, Brazil

Site Status NOT_YET_RECRUITING

Hospital Geral Universitário

Cuiabá, Mount, Brazil

Site Status NOT_YET_RECRUITING

Hospital Santa Casa de Misericórdia de Curitiba

Curitiba, Paraná, Brazil

Site Status NOT_YET_RECRUITING

Hospital Universitário Procape

Recife, Pernambuco, Brazil

Site Status NOT_YET_RECRUITING

Hospital das Clínicas da UNICAMP

Campinas, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Santa Casa de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

HC - FMUSP / Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Site Status RECRUITING

Instituto de Moléstias Cardiovasculares

São José do Rio Preto, São Paulo, Brazil

Site Status RECRUITING

Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Beneficiência Portuguesa

São Paulo, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Escola Paulista de Medicina

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Instituto Dante Pazzanese de Cardiologia

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Martino Martinelli, MD, PhD

Role: CONTACT

55 11 26615515

Sergio F Siqueira, Eng, MsC

Role: CONTACT

55 11 26615514

Facility Contacts

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Francisca TM Pereira, MD

Role: primary

Eduardo A Rocha, MD

Role: backup

Luiz P Magalhães, MD

Role: primary

Alexandro A Fagundes, MD

Role: backup

José M Baggio Jr, MD

Role: primary

Anis Rassi Jr, MD, PhD

Role: primary

Salvador Rassi, MD, PhD

Role: primary

Sérgio Rassi, MD

Role: primary

Antônio MC Lima, MD

Role: backup

Maria CV Moreira, MD, PhD

Role: primary

Thiago R Rodrigues, MD

Role: backup

Ricardo A Teixeira, MD, PhD

Role: primary

Celso S Melo, MD

Role: primary

Júlio C Oliveira, MD, PhD

Role: primary

Gerson Lemke, MD

Role: primary

José CM Jorge, MD, PhD

Role: backup

Dário Sobral Filho, MD, PhD

Role: primary

Abelardo G Escarião, MD

Role: backup

Márcio JO Figueiredo, MD, PhD

Role: primary

Antonio Vitor Moraes Jr, MD, PhD

Role: primary

+55 16 97920407

José A Marin-Neto, MD, FullProf

Role: primary

Marcelo G Leal, MD, PhD

Role: backup

Adalberto Lorga Filho, MD, PhD

Role: primary

Oswaldo T Greco, MD

Role: backup

Martino Martinelli, MD, PhD

Role: primary

55 11 26615515

Sergio F Siqueira, Eng, MsC

Role: backup

55 11 26615514

Silas S Galvão Filho, MD

Role: primary

José TM Vasconcelos, MD, PhD

Role: backup

Angelo Paola, MD, FullProf

Role: primary

Guilherme Fenelon, MD, PhD

Role: backup

Paulo TJ Medeiros, MD

Role: primary

+5511996462424

References

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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.

Reference Type DERIVED
PMID: 39356542 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24268211 (View on PubMed)

Other Identifiers

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CHAGASICS

Identifier Type: -

Identifier Source: org_study_id

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