BENEFIT: Evaluation of the Use of Antiparasital Drug (Benznidazole) in the Treatment of Chronic Chagas' Disease

NCT ID: NCT00123916

Last Updated: 2020-03-03

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

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2854 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-30

Study Completion Date

2015-08-31

Brief Summary

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Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC).

The BENEFIT study is being conducted by the Population Health Research Institute (in Hamilton, Canada) and the Institute Dante Pazzanese de Cardiologia (Sao Paulo, Brazil) together with a Steering Committee, and an independent Safety Monitoring Board.

Detailed Description

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A randomized double-blind controlled clinical trial investigating the role of benznidazole in patients with chronic Chagas' heart disease.

Chagas disease has 3 phases: acute, undetermined and chronic phases. There are no clinical trials up to date that have investigated the use of antiparasitic drugs in patients that are in the chronic phase.

This study will evaluate the efficacy and safety of benznidazole (an antiparasitic drug) in patients with chronic Chagas' heart disease. Evaluate if benznidazole, an antiparasite drug, given at a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 to 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg) - reduces morbidity and mortality in patients with Chronic Chagas' Cardiomyopathy (CCC). It will be developed in 49 study centres in Argentina, Bolivia,Brazil,Colombia, and El Salvador - countries with high incidence of Chagas Disease.

The Pilot study is evaluating if benznidazole is effective in producing parasitic cure (PCR negativization or reducing parasitic load) in chronic Chagas Disease as well as assessing the feasibility of conducting a large trial in chronic Chagas Disease in South America.

Conditions

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Chagas Disease Trypanosomiasis Heart Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Benznidazole

40 - 80 days (according to body weight) treatment with benznidazol

Group Type EXPERIMENTAL

Benznidazole

Intervention Type DRUG

Daily po Benznidazole or placebo (weight based) during 40 - 80 days (depending on body weight)

Placebo

40 - 80 days (according to body weight) treatment with matching placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 - 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg)

Interventions

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Benznidazole

Daily po Benznidazole or placebo (weight based) during 40 - 80 days (depending on body weight)

Intervention Type DRUG

Placebo

a dose calculated as 5mg/kg/day for 60 days, now administered as a fixed daily dose of 300mg during 40 - 80 days of treatment - period adjusted according to the patient's body weight to a total minimum dose of 12g (corresponding to 40kg) and a total maximum dose of 24g (corresponding to 80kg)

Intervention Type DRUG

Other Intervention Names

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Rochagan/LaFepe Rochagan/LaFepe

Eligibility Criteria

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Inclusion Criteria

* Consenting patients (between 18 and 75 years of age) with serological evidence of Chagas infection (any combination of 2 positive tests) and that have one or more of the following:
* Abnormal electrocardiogram with at least two components (complete RBBB or LBBB; left anterior or posterior fascicular block; ventricular premature beat; first degree atrioventricular \[AV\] block; Mobitz type I AV block; sinus bradycardia; primary ST-T changes; abnormal Q waves; low voltage QRS; or atrial fibrillation);
* Abnormal ECG (Mobitz type II, advanced or third degree AV block);
* Increased cardiothoracic ratio (\> 0.50);
* Complex ventricular arrythmias on 24 hour ambulatory ECG monitoring;
* Evidence of regional wall motion abnormality or reduced global left ventricular systolic function or increased left ventricular and diastolic diameter on 2D-Echo.

Exclusion Criteria

Patients will be excluded if having:

* NYHA heart failure class IV or decompensated heart failure
* Evidence of concomitant coronary artery disease (CAD) or other etiology of dilated cardiomyopathy
* Previous treatment with antitrypanosomal agents or an accepted indication for antiparasitic therapy
* Inability to comply with follow-up visits
* History of severe alcohol abuse within 2 years
* Known chronic renal or hepatic insufficiency or hepatic insufficiency
* Pregnancy or breast feeding
* Megaesophagus with swallowing impairment
* Other severe disease significantly curtailing life expectancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

World Health Organization

OTHER

Sponsor Role collaborator

Instituto Dante Pazzanese de Cardiologia

OTHER

Sponsor Role collaborator

University of Sao Paulo

OTHER

Sponsor Role collaborator

Population Health Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Salim Yusuf's office

Principal Co-Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Carlos Morillo, MD

Role: STUDY_CHAIR

Population Health Research Institute - McMaster University

Jose Antonio Marin-Neto, MD, PhD

Role: STUDY_CHAIR

University of Sao Paulo

Salim Yusuf, MD, DPh

Role: STUDY_CHAIR

Population Health Research Institute - McMaster University

Sergio Sosa-Estani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Argentina National Coordinator - CenDIE, Argentina

Fernando Rosas, M.D.

Role: PRINCIPAL_INVESTIGATOR

Fundacion Clinica Shaio, Bogota, Colombia

Locations

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BENEFIT Ivestigational Site

Buenos Aires, Apital Federal, Argentina

Site Status

BENEFIT Investigational Site

Belén de Escobar, Buenos Aires, Argentina

Site Status

BENEFIT Investigational Site

Isidro Casanova, Buenos Aires, Argentina

Site Status

BENEFIT Investigational Site

San Juan, Buenos Aires, Argentina

Site Status

BENEFIT Investigational Site

Santiago Del Estero, Buenos Aires, Argentina

Site Status

BENEFIT Investigational Site

Santiago Del Estero, Buenos Aires, Argentina

Site Status

BENEFIT Investigational Site

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

BENEFIT Investigational Site

Catamarca, Catamarca Province, Argentina

Site Status

BENEFIT Investigational Site

Charata, Chaco Province, Argentina

Site Status

BENEFIT Investigational Site

Paraná, Entre Ríos Province, Argentina

Site Status

BENEFIT Investigational Site

Buenos Aires, General Rodríguez Partido, Argentina

Site Status

BENEFIT Investigational Site

San Salvador de Jujuy, Jujuy Province, Argentina

Site Status

BENEFIT Investigational Site

Corrientes, Rosario, Santa Fe, Argentina

Site Status

BENEFIT Investigational Site

Rosario, Santa Fe Province, Argentina

Site Status

BENEFIT Investigational Site

Añatuya, Santiago del Estero Province, Argentina

Site Status

BENEFIT Investigational Site

Santiago del Estero, Sgo. Del Estero, Argentina

Site Status

BENEFIT Investigational Site

Buenos Aires, , Argentina

Site Status

BENEFIT Investigational Site

Salta, , Argentina

Site Status

BENEFIT Investigational Site

Tupiza, Potosí Department, Bolivia

Site Status

BENEFIT Investigational Site

Salvador, Bahaia, Brazil

Site Status

BENEFIT Investigational Site

Salvador, Bahaia, Brazil

Site Status

BENEFIT Investigational Site

Salvador, Bahaia, Brazil

Site Status

BENEFIT Investigational Site

Carmo, Belo Horizonte, Brazil

Site Status

BENEFIT Investigational Site

Brasília, Brazilian Federal District, Brazil

Site Status

BENEFIT Investigational Site

Goiânia, Goiás, Brazil

Site Status

BENEFIT Investigational Site

Goiânia, Goiás, Brazil

Site Status

BENEFIT Investigational Site

Goiânia, Goiás, Brazil

Site Status

BENEFIT Investigational Site

Uberaba, Minas Gerais, Brazil

Site Status

BENEFIT Investigational Site

Uberlândia, Minas Gerais, Brazil

Site Status

BENEFIT Investigational Site

Uberlândia, Minas Gerais, Brazil

Site Status

BENEFIT Investigational Site

Curitiba, Paraná, Brazil

Site Status

BENEFIT Investigational Site

Recife, Pernambuco, Brazil

Site Status

BENEFIT Investigational Site

Pelotas, Rio Grande do Sul, Brazil

Site Status

BENEFIT Investigational Site

Campinas, São Paulo, Brazil

Site Status

BENEFIT Investigational Site

Ribeirão Preto, São Paulo, Brazil

Site Status

BENEFIT Investigational Site

São José do Rio Preto, São Paulo, Brazil

Site Status

BENEFIT Investigational Site

São José do Rio Preto, São Paulo, Brazil

Site Status

BENEFIT Investigational Site

Votuporanga, São Paulo, Brazil

Site Status

BENEFIT Investigational Site

Rio de Janeiro, , Brazil

Site Status

BENEFIT Investigational Site

Rio de Janeiro, , Brazil

Site Status

BENEFIT Investigational Site

São Paulo, , Brazil

Site Status

BENEFIT Investigational Site

São Paulo, , Brazil

Site Status

BENEFIT Investigational Site

São Paulo, , Brazil

Site Status

BENEFIT Investigational Site

São Paulo, , Brazil

Site Status

BENEFIT Investigational Site

Bogotá, Bogota D.C., Colombia

Site Status

BENEFIT Investigational Site

San Gil, Santander Department, Colombia

Site Status

BENEFIT Ivestigational Site

San Salvador, , El Salvador

Site Status

Countries

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Argentina Bolivia Brazil Colombia El Salvador

References

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Marin-Neto JA, Rassi A Jr, Morillo CA, Avezum A, Connolly SJ, Sosa-Estani S, Rosas F, Yusuf S; BENEFIT Investigators. Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas' cardiomyopathy: the BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT). Am Heart J. 2008 Jul;156(1):37-43. doi: 10.1016/j.ahj.2008.04.001.

Reference Type BACKGROUND
PMID: 18585495 (View on PubMed)

Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr, Rosas F, Villena E, Quiroz R, Bonilla R, Britto C, Guhl F, Velazquez E, Bonilla L, Meeks B, Rao-Melacini P, Pogue J, Mattos A, Lazdins J, Rassi A, Connolly SJ, Yusuf S; BENEFIT Investigators. Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy. N Engl J Med. 2015 Oct;373(14):1295-306. doi: 10.1056/NEJMoa1507574. Epub 2015 Sep 1.

Reference Type DERIVED
PMID: 26323937 (View on PubMed)

Marin-Neto JA, Rassi A Jr, Avezum A Jr, Mattos AC, Rassi A, Morillo CA, Sosa-Estani S, Yusuf S; BENEFIT Investigators. The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease. Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:319-24. doi: 10.1590/s0074-02762009000900042.

Reference Type DERIVED
PMID: 19753491 (View on PubMed)

Related Links

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http://www.phri.ca

Population Health Research Institute

http://www.idpc.org.br/pesquisa/

Instituto Dante Pazzanese de Cardiologia

Other Identifiers

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CONEP-11394

Identifier Type: OTHER

Identifier Source: secondary_id

BEN01

Identifier Type: -

Identifier Source: org_study_id

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