Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE)

• Published in: Antimicrobial agents and chemotherapy Vol. 67; no. 4; p. e0119322
• Main Authors: Altcheh, Jaime, Sierra, Victor, Ramirez, Teresa, Pinto Rocha, Jimy José, Grossmann, Ulrike, Huang, Erya, Moscatelli, Guillermo, Ding, Olivia
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 18.04.2023
• Subjects: Adolescent; Antimicrobial Chemotherapy; Body Weight; Chagas Disease - drug therapy; Child; Clinical Therapeutics; Follow-Up Studies; Historically Controlled Study; Humans; Nifurtimox - adverse effects; Nitroimidazoles - adverse effects; Prospective Studies; Treatment Outcome; Trypanocidal Agents - adverse effects; follow-up; treatment; nifurtimox; seronegative conversion; pediatrics; Chagas disease; Trypanosoma cruzi
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.01193-22

Nifurtimox is recommended for the treatment of Chagas disease; however, long-term follow-up data are scarce. This prolonged follow-up phase of the prospective, historically controlled, CHICO clinical trial evaluated seronegative conversion in pediatric patients aged <18 years with Chagas disease who were followed for 4 years after nifurtimox treatment. Patients were randomly assigned 2:1 to nifurtimox 60-day or 30-day regimens comprising 10 to 20 mg/kg/day for patients aged <12 years and body weight <40 kg, and 8 to 10 mg/kg/day for those aged ≥12 years and body weight ≥40 kg. Anti-Trypanosoma cruzi antibodies decreased during the study period, achieving seronegative conversion in 16 (8.12%) and 8 (8.16%) patients in the 60-day and 30-day nifurtimox regimens, respectively, with corresponding incidence rates per 100 patients/year of seronegative conversion of 2.12 (95% confidence interval [CI]: 1.21 to 3.45) and 2.11 (95% CI: 0.91 to 4.16). Superiority of the 60-day nifurtimox regimen was confirmed by the lower limit of the 95% CI being higher than that (0%) in a historical placebo control group. Children aged <2 years at baseline were more likely to reach seronegative conversion during the 4-year follow-up than older children. At any annual follow-up visit, >90% of evaluable patients had persistently negative quantitative PCR results for T. cruzi DNA. No adverse events potentially related to treatment or caused by protocol-required procedures were documented for either treatment regimen. This study confirms the effectiveness and safety of a pediatric formulation of nifurtimox administered in an age- and weight-adjusted regimen for 60 days to treat children with Chagas disease.