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

NCT01722942 | Unknown DMC

• 1 other identifier: CHAGASICS
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 20

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).

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

Outcome Measures

Primary Outcomes (1)

• all cause mortality

  All cause mortality

  three and half years

Secondary Outcomes (5)

• Cardiac mortality

  three and half years

• Sudden cardiac death

  three and half years

• Worsening heart failure warranting hospitalization

  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

  three and half years

Other Outcomes (1)

• 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.

  three and half years

Study Arms (2)

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.

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.

Drug: amiodarone hydrochloride

Interventions

ICD implantation PROCEDURE

ventricular ICD implantation

Also known as: ICD

ICD group

amiodarone hydrochloride DRUG

amiodarone prescription

Also known as: amiodarone

Amiodarone Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• InCor Heart Institute: lead
• Ministry of Health, Brazil: collaborator
• Abbott Medical Devices: collaborator

Study Sites (20)

Hospital Universitário Walter Cantideo

Fortaleza, Ceará, Brazil

RECRUITING

Hospital Ana Nery

Salvador, Estado de Bahia, Brazil

NOT YET RECRUITING

Instituto de Cardiologia do Distrito Federal

Brasília, Federal District, Brazil

RECRUITING

Anis Rassi Hospital

Goiânia, Goiás, Brazil

NOT YET RECRUITING

Hospital das Clínicas de Goiania

Goiânia, Goiás, Brazil

RECRUITING

Santa Casa de Goiania

Goiânia, Goiás, Brazil

NOT YET RECRUITING

Hospital Felício Rocho

Belo Horizonte, Minas Gerais, Brazil

NOT YET RECRUITING

Hospital das Clínicas Samuel Libânio

Pouso Alegre, Minas Gerais, Brazil

NOT YET RECRUITING

Hospital Escola da Universidade Federal do Triângulo Mineiro

Uberaba, Minas Gerais, Brazil

NOT YET RECRUITING

Hospital Geral Universitário

Cuiabá, Mount, Brazil

NOT YET RECRUITING

Hospital Santa Casa de Misericórdia de Curitiba

Curitiba, Paraná, Brazil

NOT YET RECRUITING

Hospital Universitário Procape

Recife, Pernambuco, Brazil

NOT YET RECRUITING

Hospital das Clínicas da UNICAMP

Campinas, São Paulo, Brazil

NOT YET RECRUITING

Santa Casa de Ribeirão Preto

Ribeirão Preto, São Paulo, 14080-000, Brazil

NOT YET RECRUITING

HC - FMUSP / Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

RECRUITING

Instituto de Moléstias Cardiovasculares

São José do Rio Preto, São Paulo, Brazil

RECRUITING

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

São Paulo, São Paulo, 05403000, Brazil

RECRUITING

Beneficiência Portuguesa

São Paulo, São Paulo, Brazil

NOT YET RECRUITING

Escola Paulista de Medicina

São Paulo, São Paulo, Brazil

RECRUITING

Instituto Dante Pazzanese de Cardiologia

São Paulo, São Paulo, Brazil

RECRUITING

Related Publications (2)

• 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.

  PMID: 39356542 DERIVED

• 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.

  PMID: 24268211 DERIVED

MeSH Terms

Conditions

Chagas Cardiomyopathy; Death, Sudden, Cardiac

Interventions

Amiodarone

Condition Hierarchy (Ancestors)

Chagas Disease; Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Heart Arrest; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Martino Martinelli, Prof.

  InCor Heart Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martino Martinelli, MD, PhD

CONTACT

55 11 26615515; martino@incor.usp.br

Sergio F Siqueira, Eng, MsC

CONTACT

55 11 26615514; siqueira@incor.usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, MD

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 7, 2012
• Study Start: October 6, 2014
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: August 30, 2021

Record last verified: 2021-08

Locations

BR (20)