Prospective Study of a Pediatric Nifurtimox Formulation for Chagas' Disease
Condition: Chagas Disease
MeSH terms: Chagas Disease
Intervention: Nifurtimox (Lampit, BAYA2502); Placebo
Intervention description: For pediatric subjects with body weight ≤ 40 kg: dosage 10 to 20 mg/kg/day in three divided doses.
For pediatric subjects with body weight > 40 kg: 8 - 10 mg/kg/day in three divided doses.
60 days of nifurtimox treatment; Matching placebo
Intervention MeSH terms: Nifurtimox
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 330.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The study consists of two parts. Part I (CHICO) was designed to develop a better
      understanding of the efficacy, safety and pharmacokinetics of nifurtimox in children with a
      diagnosis of Chagas' disease (Trypanosoma cruzi infection) using pediatric formulations. Part
      II (CHICO SECURE) was designed at request of the FDA to assess the incidence of sero-negative
      conversion in children with diagnosis of Chagas' disease treated with nifurtimox.
    

Eligibility criteria:

        Inclusion Criteria:

        Part 1:

          -  Male and female pediatric subjects aged 0 days to younger than 18 years

          -  Chagas' disease diagnosed/ confirmed for a) Subjects < 8 months of age at
             randomization must demonstrate direct observation of Trypanosoma cruzi by
             concentration test; b) Subjects ≥ 8 months to < 18 years of age at randomization must
             demonstrate a positive conventional ELISA result for both recombinant ELISA and total
             purified antigen ELISA

        Part 2:

        - Male and female subjects who were randomized and received at least one dose of their
        assigned 60- or 30-day regimen of nifurtimox treatment

        Exclusion Criteria:

        Part 1:

          -  Subjects aged 0 to 27 days who, at birth, were pre-term, weighed less than 2500 g, or
             had a maximum Apgar score < 7 at 5 minutes

          -  Known evidence of Chagas' disease-related cardiomyopathy/ Chagas' heart disease

          -  Known evidence of Chagas' disease-related gastrointestinal dysfunction (e.g.
             megaoesophagus, megacolon, or both) or Chagas' digestive disease

          -  Serious manifestations of acute Chagas' disease, including myocarditis,
             meningoencephalitis, or pneumonitis

          -  Known evidence of Chagas' disease-related damage to the peripheral nervous system or
             peripheral neuropathy

          -  Clinically significant psychiatric disorder (e.g. moderate to severe depression,
             severe anxiety, or psychosis) or epilepsy

          -  Subjects with contraindications/ warnings to nifurtimox administration, or with
             conditions that may increase the risk of the undesirable effects of nifurtimox

          -  Subjects who have had previous treatment with trypanocidal agents or an accepted
             indication for antiparasitic therapy (e.g. reactivation of Chagas' infection due to
             immunosuppression by several diseases or treatment with steroids)

          -  Subjects living in housing conditions where there is no active or effective vector
             control to Trypanosoma cruzi reinfection as determined by Ministry of Health
             guidelines in each country

        Part 2:

          -  Subjects with acute or chronic health conditions or congenital disorders which, in the
             opinion of the investigator, would make them unsuitable for participation in the
             clinical study

          -  Subjects living in housing conditions where there is no active or effective
             vector-control to Trypanosoma cruzi reinfection as determined by Ministry of Health
             guideline of the respective country

          -  Subjects with clinical manifestations of Chagas' disease-related gastrointestinal
             dysfunction or serious manifestations of acute Chagas' disease

          -  Immuno-compromised subjects (e.g. with human immunodeficiency virus or treated with
             immunosuppressive drugs)