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

Heart Disease Clinical Trial

— BENEFIT  

Official title:

Benznidazole Evaluation for Interrupting Trypanosomiasis - The BENEFIT Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00123916
• Other study ID #: BEN01
• Secondary ID: CONEP-11394
• Status: Completed
• Phase: Phase 3
• Start date: November 2004
• Est. completion date: August 2015

Study information

• Verified date: February 2020
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2854
• Est. completion date: August 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chagas Disease
• Heart Disease
• Heart Diseases
• Trypanosomiasis

Intervention

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

Locations

Country	Name	City	State
Argentina	BENEFIT Investigational Site	Añatuya	Santiago Del Estero
Argentina	BENEFIT Investigational Site	Belén De Escobar	Buenos Aires
Argentina	BENEFIT Investigational Site	Buenos Aires	General Rodríguez Partido
Argentina	BENEFIT Investigational Site	Buenos Aires
Argentina	BENEFIT Investigational Site	Charata	Chaco
Argentina	BENEFIT Investigational Site	Ciudad Autónoma de Buenos Aires	Capital Federal
Argentina	BENEFIT Ivestigational Site	Ciudad Autónoma de Buenos Aires	Apital Federal
Argentina	BENEFIT Investigational Site	Corrientes	Rosario, Santa Fe
Argentina	BENEFIT Investigational Site	Isidro Casanova	Buenos Aires
Argentina	BENEFIT Investigational Site	Paraná	Entre Rios
Argentina	BENEFIT Investigational Site	Rosario	Santa Fe
Argentina	BENEFIT Investigational Site	Salta
Argentina	BENEFIT Investigational Site	San Fernando del Valle de Catamarca	Catamarca
Argentina	BENEFIT Investigational Site	San Juan	Buenos Aires
Argentina	BENEFIT Investigational Site	San Salvador de Jujuy	Jujuy
Argentina	BENEFIT Investigational Site	Santiago del Estero	Buenos Aires
Argentina	BENEFIT Investigational Site	Santiago del Estero	Buenos Aires
Argentina	BENEFIT Investigational Site	Santiago Del Estero	Sgo. Del Estero
Bolivia	BENEFIT Investigational Site	Tupiza	Potosi
Brazil	BENEFIT Investigational Site	Brasília	Brazilian Federal District
Brazil	BENEFIT Investigational Site	Campinas	São Paulo
Brazil	BENEFIT Investigational Site	Carmo	Belo Horizonte
Brazil	BENEFIT Investigational Site	Curitiba	Parana
Brazil	BENEFIT Investigational Site	Goiânia	GO
Brazil	BENEFIT Investigational Site	Goiânia	GO
Brazil	BENEFIT Investigational Site	Goiânia	GO
Brazil	BENEFIT Investigational Site	Pelotas	Rio Grande Do Sul
Brazil	BENEFIT Investigational Site	Recife	Pernambuco
Brazil	BENEFIT Investigational Site	Ribeirão Preto	São Paulo
Brazil	BENEFIT Investigational Site	Rio de Janeiro
Brazil	BENEFIT Investigational Site	Rio de Janeiro
Brazil	BENEFIT Investigational Site	Salvador	Bahaia
Brazil	BENEFIT Investigational Site	Salvador	Bahaia
Brazil	BENEFIT Investigational Site	Salvador	Bahaia
Brazil	BENEFIT Investigational Site	São José do Rio Preto	São Paulo
Brazil	BENEFIT Investigational Site	São José do Rio Preto	São Paulo
Brazil	BENEFIT Investigational Site	São Paulo
Brazil	BENEFIT Investigational Site	São Paulo
Brazil	BENEFIT Investigational Site	São Paulo
Brazil	BENEFIT Investigational Site	São Paulo
Brazil	BENEFIT Investigational Site	Uberaba	Minas Gerais
Brazil	BENEFIT Investigational Site	Uberlandia	MG
Brazil	BENEFIT Investigational Site	Uberlândia	MG
Brazil	BENEFIT Investigational Site	Votuporanga	São Paulo
Colombia	BENEFIT Investigational Site	Bogota	Bogotá
Colombia	BENEFIT Investigational Site	San Gil	Santander
El Salvador	BENEFIT Ivestigational Site	San Salvador

Sponsors (5)

Lead Sponsor	Collaborator
Population Health Research Institute	Canadian Institutes of Health Research (CIHR), Instituto Dante Pazzanese de Cardiologia, University of Sao Paulo, World Health Organization

Countries where clinical trial is conducted

Argentina,  Bolivia,  Brazil,  Colombia,  El Salvador, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Progression of NYHA functional class by at least one category		through study completion, an average of 5 years
Secondary	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
Secondary	Progression of New York Heart Association (NYHA) functional class by at least one category		through study completion, an average of 5 years
Secondary	Evaluation of safety (adverse events: dermatitis, peripheral neuropathy, gastro-intestinal intolerance, leucopenia [2500 x 10^9 L]), tolerance and adherence to treatment		through study completion, an average of 5 years
Secondary	Determination of the efficacy of benznidazole in patients with Chronic Chagas heart disease based on a 50% reduction in both qualitative and quantitative PCR.	Polymerase Chain Reaction study on patient's blood samples and report negativization at the end of treatment, 2Y and final visit.	through study completion, an average of 5 years
Secondary	Safety and tolerability of benznidazole		through study completion, an average of 5 years

External Links

•   Instituto Dante Pazzanese de Cardiologia
•   Population Health Research Institute