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

This study is currently recruiting participants.
Verified June 2005 by Population Health Research Institute
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
World Health Organization
Dante Pazzanese Institute
Hospital das Clinicas de Ribeirao Preto/USP
Information provided by:
Population Health Research Institute
ClinicalTrials.gov Identifier:
NCT00123916
First received: July 21, 2005
Last updated: August 1, 2011
Last verified: June 2005
History of Changes
  Purpose

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 an independent Steering Committee.


Condition Intervention Phase
Chagas Disease
Trypanosomiasis
Heart Disease
 Drug: Benznidazole
Drug: Placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Benznidazole Evaluation for Interrupting Trypanosomiasis - The BENEFIT Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Population Health Research Institute:

Primary Outcome Measures:
  • It will also evaluate the cardiovascular events of the large outcome trial, the first occurrence of any of the following clinically significant outcomes: Death [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Resuscitated cardiac arrest, requiring defibrillator or cardioversion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Cardiac arrest secondary to bradyarrythmias, ventricular tachycardia, ventricular flutter, or ventricular fibrillation that requires CPR and or electrical cardioversion or defibrillation.

  • Documented sustained ventricular tachycardia requiring cardioversion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • New development of symptomatic congestive heart failure [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Pacemaker or implantable cardiac defibrillator implantation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Stroke or any other thromboembolic event in patients with no prior thromboembolic phenomena [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Heart Transplant [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • New development of any of the following echo changes clinically indicated or done for the trial: Segmental wall motion abnormalities [ Time Frame: 2 year and end of study ] [ Designated as safety issue: No ]
  • Ventricular aneurysm [ Time Frame: 2 year and end of study ] [ Designated as safety issue: No ]
  • Reduction in left ventricular (LV) ejection fraction > 5% [ Time Frame: 2 year and end of study ] [ Designated as safety issue: No ]
  • Increase in left ventricular diastolic dysfunction (LVDD) > 5.0 mm compared with baseline [ Time Frame: 2 year and end of study ] [ Designated as safety issue: No ]
  • New 12 lead electrocardiogram (ECG) alterations (complete bundle branch block; fascicular block, advanced atrio-ventricular block, atrial fibrillation, etc.) [ Time Frame: 2 year and end of study ] [ Designated as safety issue: No ]
  • Progression of New York Heart Association (NYHA) functional class by at least one category [ Time Frame: end of study ] [ Designated as safety issue: No ]
  • Evaluation of safety (adverse events: dermatitis, peripheral neuropathy, gastro-intestinal intolerance, leucopenia [2500 x 10^9 L]), tolerance and adherence to treatment [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine the efficacy of benznidazole in patients with Chronic Chagas heart disease based on a 50% reduction in both qualitative and quantitative PCR. [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of benznidazole [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1000
Study Start Date: November 2004
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Benznidazole
60 days treatment with benznidazol
 Drug: Benznidazole
Daily po Benznidazole or placebo (weight based) during 60 days,
Other Name: Rochagan
Drug: Placebo
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)
Other Name: Rochagan
Placebo Comparator: Placebo
60 days treatment with matching placebo
 Drug: Benznidazole
Daily po Benznidazole or placebo (weight based) during 60 days,
Other Name: Rochagan
Drug: Placebo
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)
Other Name: Rochagan

Detailed 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 54 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00123916

Contacts
Contact: Carlos A. Morillo, MD 1-905-527-4322 ext 40311 benefit@phri.ca
Contact: Alvaro Avezum, MD,PhD 55-11-5085-6204 benefit@dantepazzanese.org.br

  Show 47 Study Locations
Sponsors and Collaborators
Population Health Research Institute
Canadian Institutes of Health Research (CIHR)
World Health Organization
Dante Pazzanese Institute
Hospital das Clinicas de Ribeirao Preto/USP
Investigators
Study Chair: Carlos Morillo, MD, FRCPC, FAC Population Health Research Institute - McMaster University
Study Chair: Jose Antonio Marin-Neto, MD, PhD,FACC Hospital das Clinicas de Ribeirao Preto/USP
Study Chair: Salim Yusuf, MD, DPh, FRCPC Population Health Research Institute - McMaster University
Principal Investigator: Sergio Sosa-Estani, MD Argentina National Coordinator - CenDIE, Argentina
Principal Investigator: Fernando Rosas Fundacion Clinica Shaio, Bogota, Colombia
  More Information

Additional Information:
Population Health Research Institute  This link exits the ClinicalTrials.gov site
Instituto Dante Pazzanese de Cardiologia  This link exits the ClinicalTrials.gov site

No publications provided by Population Health Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Dante Pazzanese, Instituto de Pesquisa, Dante Pazzanese
ClinicalTrials.gov Identifier: NCT00123916     History of Changes
Other Study ID Numbers: BEN01, CONEP-11394
Study First Received: July 21, 2005
Last Updated: August 1, 2011
Health Authority: Brazil: National Committee of Ethics in Research
Canada: Ethics Review Committee
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by Population Health Research Institute:
Chagas Disease
Trypanosomiasis
Benznidazole
Chronic Heart disease
Trypanosoma Cruzi

Additional relevant MeSH terms:
Heart Diseases
Trypanosomiasis
Chagas Disease
Cardiovascular Diseases
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Benzonidazole
Immunosuppressive Agents
 Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013