Population Pharmacokinetics of Benznidazole in Children With Chagas Disease

Study Overview
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Brief Summary
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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.

Official Title
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Population Pharmacokinetics Study of Benznidazole in Children With Chagas Disease

Conditions
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Chagas Disease

Intervention / Treatment
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* Drug: Benznidazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Benznidazole<br>Treatment of pediatric Chagas disease with benznidazole | Drug: Benznidazole<br>* benznidazole (RADANIL®, Roche) 5-8 mg/kg/d bid PO for 60 days<br>* Other names: Niños con Chagas en Tratamiento con Benznidazol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of Population pharmacokinetics parameters of benznidazole (i.e. median population clearance, absorption and volume of distribution, and their respective inter-individual variabilities) |  | 2 months (treatment period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | 2 months (treatment period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chagas disease, Pediatrics, benznidazole, population pharmacokinetics, neglected diseases, parasitology, pediatric clinical pharmacology