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

NCT00123916 | Completed Phase 3 DMC

• 2 other identifiers: BEN01CONEP-11394
• Study Type: interventional
• Target: 2,854
• Locations: 5 countries
• Sites: 47

Brief Summary

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.

Conditions

Chagas Disease; Trypanosomiasis; Heart Disease

Keywords

Chagas Disease; Trypanosomiasis; Benznidazole; Chronic Heart disease; Trypanosoma Cruzi

Outcome Measures

Primary Outcomes (1)

• Composite of First of cardiovascular events: Death, Resuscitated Cardiac Arrest, Sustained VentricularTachycardia, New/worsening Heart Failure, New Pacemaker/ICD, Stroke/TIA or other Embolic Events, Cardiac Transplant.

  Composite cardiovascular outcome,

  through study completion, an average of 5 years

Secondary Outcomes (8)

• New development of any of the following echo changes, segmental wall motion abnormalities, ventricular aneurysm, reduction in LV ejection fraction >5%, increase in LVDD> 5 mm compared to baseline.

  through study completion, an average of 5 years

• New 12 lead ECG alterations (complete bundle branch block, fascicular block, advanced atrio-ventricular block, atrial fibrillation, etc).

  through study completion, an average of 5 years

• Progression of NYHA functional class by at least one category

  through study completion, an average of 5 years

• New 12 lead electrocardiogram (ECG) alterations (complete bundle branch block; fascicular block, advanced atrio-ventricular block, atrial fibrillation, etc.)

  through study completion, an average of 5 years

• Progression of New York Heart Association (NYHA) functional class by at least one category

  through study completion, an average of 5 years

Study Arms (2)

Benznidazole

EXPERIMENTAL

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

Drug: Benznidazole

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Benznidazole DRUG

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

Also known as: Rochagan/LaFepe

Benznidazole

Placebo 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)

Also known as: Rochagan/LaFepe

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Population Health Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• World Health Organization: collaborator
• Instituto Dante Pazzanese de Cardiologia: collaborator
• University of Sao Paulo: collaborator

Study Sites (47)

BENEFIT Ivestigational Site

Buenos Aires, Apital Federal, 3556, Argentina

Location

BENEFIT Investigational Site

Belén de Escobar, Buenos Aires, 1753, Argentina

Location

BENEFIT Investigational Site

Isidro Casanova, Buenos Aires, 1282, Argentina

Location

BENEFIT Investigational Site

San Juan, Buenos Aires, 1625, Argentina

Location

BENEFIT Investigational Site

Santiago Del Estero, Buenos Aires, 4200, Argentina

Location

BENEFIT Investigational Site

Santiago Del Estero, Buenos Aires, 5400, Argentina

Location

BENEFIT Investigational Site

Buenos Aires, Buenos Aires F.D., 1063, Argentina

Location

BENEFIT Investigational Site

Catamarca, Catamarca Province, Argentina

Location

BENEFIT Investigational Site

Charata, Chaco Province, H3730AVI, Argentina

Location

BENEFIT Investigational Site

Paraná, Entre Ríos Province, 3100, Argentina

Location

BENEFIT Investigational Site

Buenos Aires, General Rodríguez Partido, Argentina

Location

BENEFIT Investigational Site

San Salvador de Jujuy, Jujuy Province, 4600, Argentina

Location

BENEFIT Investigational Site

Corrientes, Rosario, Santa Fe, 3400, Argentina

Location

BENEFIT Investigational Site

Rosario, Santa Fe Province, 2000, Argentina

Location

BENEFIT Investigational Site

Añatuya, Santiago del Estero Province, 3760, Argentina

Location

BENEFIT Investigational Site

Santiago del Estero, Sgo. Del Estero, 4200, Argentina

Location

BENEFIT Investigational Site

Buenos Aires, Argentina

Location

BENEFIT Investigational Site

Salta, A4406CLA, Argentina

Location

BENEFIT Investigational Site

Tupiza, Potosí Department, Bolivia

Location

BENEFIT Investigational Site

Salvador, Bahaia, 40050-410, Brazil

Location

BENEFIT Investigational Site

Salvador, Bahaia, 40110-909, Brazil

Location

BENEFIT Investigational Site

Salvador, Bahaia, 40425-060, Brazil

Location

BENEFIT Investigational Site

Carmo, Belo Horizonte, 30130-690, Brazil

Location

BENEFIT Investigational Site

Brasília, Brazilian Federal District, 70658-700, Brazil

Location

BENEFIT Investigational Site

Goiânia, Goiás, 74110-010, Brazil

Location

BENEFIT Investigational Site

Goiânia, Goiás, 74110-020, Brazil

Location

BENEFIT Investigational Site

Goiânia, Goiás, 74605-050, Brazil

Location

BENEFIT Investigational Site

Uberaba, Minas Gerais, 38010-160, Brazil

Location

BENEFIT Investigational Site

Uberlândia, Minas Gerais, 38025-440, Brazil

Location

BENEFIT Investigational Site

Uberlândia, Minas Gerais, 38400-299, Brazil

Location

BENEFIT Investigational Site

Curitiba, Paraná, 80060-900, Brazil

Location

BENEFIT Investigational Site

Recife, Pernambuco, 50100-130, Brazil

Location

BENEFIT Investigational Site

Pelotas, Rio Grande do Sul, 96015-290, Brazil

Location

BENEFIT Investigational Site

Campinas, São Paulo, 13059-740, Brazil

Location

BENEFIT Investigational Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

BENEFIT Investigational Site

São José do Rio Preto, São Paulo, 15015-210, Brazil

Location

BENEFIT Investigational Site

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

BENEFIT Investigational Site

Votuporanga, São Paulo, 15500-003, Brazil

Location

BENEFIT Investigational Site

Rio de Janeiro, 21040-360, Brazil

Location

BENEFIT Investigational Site

Rio de Janeiro, 21941-913, Brazil

Location

BENEFIT Investigational Site

São Paulo, 01417 010, Brazil

Location

BENEFIT Investigational Site

São Paulo, 04012-909, Brazil

Location

BENEFIT Investigational Site

São Paulo, 05403-000, Brazil

Location

BENEFIT Investigational Site

São Paulo, 05403-901, Brazil

Location

BENEFIT Investigational Site

Bogotá, Bogota D.C., Colombia

Location

BENEFIT Investigational Site

San Gil, Santander Department, Colombia

Location

BENEFIT Ivestigational Site

San Salvador, El Salvador

Location

Related Publications (3)

• 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.

  PMID: 18585495 BACKGROUND

• 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.

  PMID: 26323937 DERIVED

• 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.

  PMID: 19753491 DERIVED

Related Links

• Population Health Research Institute
• Instituto Dante Pazzanese de Cardiologia

MeSH Terms

Conditions

Chagas Disease; Trypanosomiasis; Heart Diseases

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Cardiovascular Diseases

Study Officials

• Carlos Morillo, MD

  Population Health Research Institute - McMaster University

  STUDY CHAIR

• Jose Antonio Marin-Neto, MD, PhD

  University of Sao Paulo

  STUDY CHAIR

• Salim Yusuf, MD, DPh

  Population Health Research Institute - McMaster University

  STUDY CHAIR

• Sergio Sosa-Estani, MD, PhD

  Argentina National Coordinator - CenDIE, Argentina

  PRINCIPAL INVESTIGATOR

• Fernando Rosas, M.D.

  Fundacion Clinica Shaio, Bogota, Colombia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Co-Investigator

Study Record Dates

• First Submitted: July 21, 2005
• First Posted: July 26, 2005
• Study Start: November 1, 2004
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2015
• Last Updated: March 3, 2020

Record last verified: 2020-02

Locations

BR (25); CO (2); AR (18); BO (1); EL (1)