Population Pharmacokinetics of Benznidazole in Children With Chagas Disease

NCT00699387 | Completed DMC

• 1 other identifier: CHAGAS-CHILDREN-POPPK
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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

Keywords

Chagas disease; Pediatrics; benznidazole; population pharmacokinetics; neglected diseases; parasitology; pediatric clinical pharmacology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Adverse events

  2 months (treatment period)

Study Arms (1)

Benznidazole

EXPERIMENTAL

Treatment of pediatric Chagas disease with benznidazole

Drug: Benznidazole

Interventions

Benznidazole DRUG

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

Also known as: Children with Chagas Disease Treated with Benznidazole, Niños con Chagas en Tratamiento con Benznidazol

Benznidazole

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital de Niños R. Gutierrez de Buenos Aires: lead
• Thrasher Research Fund: collaborator
• The Hospital for Sick Children: collaborator
• Fundacion Bunge y Born (Argentina): collaborator
• Universidad Nacional de La Plata: collaborator
• Consejo de Investigacion en Salud Gobierno de Buenos Aires: collaborator

Study Sites (1)

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

Buenos Aires, Buenos Aires, 1425, Argentina

Location

Related Publications (1)

• 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.

  PMID: 24853169 DERIVED

MeSH Terms

Conditions

Chagas Disease; Neglected Diseases

Interventions

benzonidazole

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jaime Altcheh, MD

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

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 16, 2008
• First Posted: June 18, 2008
• Study Start: April 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: August 1, 2011

Record last verified: 2011-07

Locations

AR (1)