Population Pharmacokinetics of Benznidazole in Children With Chagas Disease

This study has been completed.
Sponsor:
Collaborators:
Thrasher Research Fund
The Hospital for Sick Children
Fundacion Bunge y Born (Argentina)
Universidad Nacional de La Plata
Consejo de Investigacion en Salud Gobierno de Buenos Aires
Information provided by:
Hospital de Niños R. Gutierrez de Buenos Aires
ClinicalTrials.gov Identifier:
NCT00699387
First received: June 16, 2008
Last updated: July 29, 2011
Last verified: July 2011
  Purpose

Background: Chagas disease is a parasitic infection caused by the Trypanosome cruzi. The initial phase of the infection happens mainly in children. Up to 10% of infected children die. Survivors often develop chronic infection leading to heart disease and other complications in 30% of patients. These complications often result in death or severe handicaps in early adulthood, depriving societies of individuals in their most productive years.

There are 20 million people infected in Latin America. Complications lead to 20,000 deaths every year.

Treatment during the acute phase with benznidazole leads to a high cure rate. However, there are very few studies of this drug and virtually none in children, even though benznidazole was developed over 30 years ago.

Hypotheses and Specific Aims: We hypothesize that the pharmacokinetics of benznidazole in children is different from adults, and that obtaining information on how it is absorbed, distributed and eliminated in children will allow optimization of treatment of Chagas disease in this population. This will in turn improve the outlook for children by reducing mortality and long term complications. We aim to study the pharmacokinetics of benznidazole in children receiving the drug for treatment of Chagas disease, and to correlate it with treatment effectiveness and incidence of adverse effects.

Potential Impact: This novel knowledge will allow better and more rational approaches to the treatment of Chagas disease. It will also set the foundation for further studies that will be able to test improved therapies that may increase treatment response in vulnerable children.


Condition Intervention
Chagas Disease
Drug: Benznidazole

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Population Pharmacokinetics Study of Benznidazole in Children With Chagas Disease

Resource links provided by NLM:


Further study details as provided by Hospital de Niños R. Gutierrez de Buenos Aires:

Primary Outcome Measures:
  • Description of Population pharmacokinetics parameters of benznidazole (i.e. median population clearance, absorption and volume of distribution, and their respective inter-individual variabilities) [ Time Frame: 2 months (treatment period) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events [ Time Frame: 2 months (treatment period) ] [ Designated as safety issue: Yes ]

Enrollment: 37
Study Start Date: April 2007
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Benznidazole
Treatment of pediatric Chagas disease with benznidazole
Drug: Benznidazole
benznidazole (RADANIL®, Roche) 5-8 mg/kg/d bid PO for 60 days
Other Names:
  • Children with Chagas Disease Treated with Benznidazole
  • Niños con Chagas en Tratamiento con Benznidazol

  Eligibility

Ages Eligible for Study:   2 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children 2 - 12 years old of both sexes, with a diagnosis of Chagas' disease and eligible for treatment with benznidazole, as per current treatment protocols.
  • Chagas disease diagnostic criteria: At least 2 positive serological tests for Trypanosoma cruzi infection (ELISA, hemoagglutination, particle agglutination tests).
  • Informed consent signed by the parents, and consent or assent of the patients (according to age and consenting capacity).

Exclusion Criteria:

  • Patients with a history of hypersensitivity to benznidazole or any of the drug excipients
  • Immunocompromised patients
  • Altered hepatic function (increase in AST/ALT x3 or bilirubin x3) or altered renal function (increase in creatinine x3)
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00699387

Locations
Argentina
Parasitology Division, Children's Hospital "R Gutierrez" of Buenos Aires
Buenos Aires, Argentina, 1425
Sponsors and Collaborators
Hospital de Niños R. Gutierrez de Buenos Aires
Thrasher Research Fund
The Hospital for Sick Children
Fundacion Bunge y Born (Argentina)
Universidad Nacional de La Plata
Consejo de Investigacion en Salud Gobierno de Buenos Aires
Investigators
Study Director: Jaime Altcheh, MD Parasitology Service, Children's Hospital "R. Gutierrez" of Buenos Aires
Principal Investigator: Facundo Garcia Bournissen, MD Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, University of Toronto
Principal Investigator: Norberto Giglio, MD Epidemiology Service, Children's Hospital "R. Gutierrez" of Buenos Aires
Principal Investigator: Gideon Koren, MD Division of Clinical Pharmacology &Toxicology, Hospital for Sick Children, University of Toronto
Principal Investigator: Oscar Della Vedova Universidad Nacional de La Plata
Principal Investigator: Guido Mastrantonio Facultad de Ciencias Exactas, Universidad Nacional de La Plata
  More Information

No publications provided by Hospital de Niños R. Gutierrez de Buenos Aires

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Jaime Altcheh, Servicio de Parasitología, Hospital de Niños "R Gutiérrez" de Buenos Aires
ClinicalTrials.gov Identifier: NCT00699387     History of Changes
Other Study ID Numbers: CHAGAS-CHILDREN-POPPK
Study First Received: June 16, 2008
Last Updated: July 29, 2011
Health Authority: Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by Hospital de Niños R. Gutierrez de Buenos Aires:
Chagas disease
Pediatrics
benznidazole
population pharmacokinetics
neglected diseases
parasitology
pediatric clinical pharmacology

Additional relevant MeSH terms:
Chagas Disease
Trypanosomiasis
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 August 20, 2014