Population Pharmacokinetics of Benznidazole in Children With Chagas Disease

NCT ID: NCT00699387

Last Updated: 2011-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2011-05-31

Brief Summary

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.

Conditions

Chagas Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Benznidazole

Treatment of pediatric Chagas disease with benznidazole

Group Type: EXPERIMENTAL

Benznidazole

Intervention Type: DRUG

benznidazole (RADANIL®, Roche) 5-8 mg/kg/d bid PO for 60 days

Interventions

Benznidazole

benznidazole (RADANIL®, Roche) 5-8 mg/kg/d bid PO for 60 days

Intervention Type: DRUG

Other Intervention Names

Children with Chagas Disease Treated with Benznidazole; Niños con Chagas en Tratamiento con Benznidazol

Eligibility 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: collaborator

Fundacion Bunge y Born (Argentina)

UNKNOWN

Sponsor Role: collaborator

Universidad Nacional de La Plata

OTHER

Sponsor Role: collaborator

Consejo de Investigacion en Salud Gobierno de Buenos Aires

OTHER

Sponsor Role: collaborator

Hospital de Niños R. Gutierrez de Buenos Aires

OTHER

Sponsor Role: lead

Responsible Party

Servicio de Parasitología, Hospital de Niños "R Gutiérrez" de Buenos Aires

Principal Investigators

Jaime Altcheh, MD

Role: STUDY_DIRECTOR

Parasitology Service, Children's Hospital "R. Gutierrez" of Buenos Aires

Facundo Garcia Bournissen, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, University of Toronto

Norberto Giglio, MD

Role: PRINCIPAL_INVESTIGATOR

Epidemiology Service, Children's Hospital "R. Gutierrez" of Buenos Aires

Gideon Koren, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Clinical Pharmacology &Toxicology, Hospital for Sick Children, University of Toronto

Oscar Della Vedova

Role: PRINCIPAL_INVESTIGATOR

Universidad Nacional de La Plata

Guido Mastrantonio

Role: PRINCIPAL_INVESTIGATOR

Facultad de Ciencias Exactas, Universidad Nacional de La Plata

Locations

Parasitology Division, Children's Hospital "R Gutierrez" of Buenos Aires

Buenos Aires, Buenos Aires, Argentina

Countries

Argentina

References

Altcheh J, Moscatelli G, Mastrantonio G, Moroni S, Giglio N, Marson ME, Ballering G, Bisio M, Koren G, Garcia-Bournissen F. Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults. PLoS Negl Trop Dis. 2014 May 22;8(5):e2907. doi: 10.1371/journal.pntd.0002907. eCollection 2014 May.

Reference Type: DERIVED

PMID: 24853169 (View on PubMed)

Other Identifiers

CHAGAS-CHILDREN-POPPK

Identifier Type: -

Identifier Source: org_study_id