Clinical trial NCT00699387: Population Pharmacokinetics of Benznidazole in Children With Chagas Disease
Official title: Population Pharmacokinetics Study of Benznidazole in Children With Chagas Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chagas Disease
Keywords: Chagas disease
Pediatrics
benznidazole
population pharmacokinetics
neglected diseases
parasitology
pediatric clinical pharmacology
Lead sponsor: Hospital de Niños R. Gutierrez de Buenos Aires
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
name: The Hospital for Sick Children
name: Fundacion Bunge y Born (Argentina)
name: Universidad Nacional de La Plata
name: Consejo de Investigacion en Salud Gobierno de Buenos Aires
First posted: 2008-06-18
Enrollment: 37
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Description of Population pharmacokinetics parameters of benznidazole (i.e. median population clearance, absorption and volume of distribution, and their respective inter-individual variabilities)
timeFrame: 2 months (treatment period)
Secondary outcomes:
measure: Adverse events
timeFrame: 2 months (treatment period)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Parasitology Division, Children's Hospital "R Gutierrez" of Buenos Aires
Study officials:
affiliation: Parasitology Service, Children's Hospital "R. Gutierrez" of Buenos Aires
name: Jaime Altcheh, MD
role: STUDY_DIRECTOR
affiliation: Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, University of Toronto
name: Facundo Garcia Bournissen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Epidemiology Service, Children's Hospital "R. Gutierrez" of Buenos Aires
name: Norberto Giglio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Clinical Pharmacology &Toxicology, Hospital for Sick Children, University of Toronto
name: Gideon Koren, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad Nacional de La Plata
name: Oscar Della Vedova
role: PRINCIPAL_INVESTIGATOR
affiliation: Facultad de Ciencias Exactas, Universidad Nacional de La Plata
name: Guido Mastrantonio
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.