Cutaneous reactions during treatment with Nifurtimox or Benznidazole among Trypanosoma cruzi seropositive adults without symptomatic cardiomyopathy: A safety sub analysis of a placebo-controlled randomised trial.

Abstract

Objectives: To determine, in a randomised placebo-controlled trial, if cutaneous adverse reactions during treatment (CARDT) with Benznidazole occur as often as with Nifurtimox, and whether the dose and duration of treatment change that frequency.

Methods: We conducted the EQUITY trial (NCT02369978), allocating Trypanosoma cruzi seropositive adults with no apparent clinical disease to a 120-day, blinded treatment with Benznidazole, Nifurtimox, or Placebo (ratio 2:2:1). Active treatment groups included either 60-day conventional-dose (60CD) regimens (Benznidazole 300 mg/day or Nifurtimox 480 mg/day, followed or preceded by, 60 days of placebo) or 120-day half-dose (120HD) regimens (Benznidazole 150 mg/day or Nifurtimox 240 mg/day). CARDT had blinded adjudication as moderate to severe during the follow-up visits.

Results: Among 307 participants, 42 CARDT (17.1%, 95% confidence interval [CI] 12.6-22.4) occurred in 246 receiving active treatment, compared to two CARDT (3.3%, 95% CI 0.0-11.3) in 61 participants receiving placebo. In 122 patients treated with Benznidazole, there were 31 CARDT (25.4%, including eight severe), compared to 11 CARDT (8.9%, including four severe) in 124 individuals treated with Nifurtimox (p < 0.001). Among the 125 participants assigned to the 120HD regimen, there were 26 CARDT (20.8%, including six severe), compared to 16 CARDT (13.2%, including six severe) among 121 in the 60CD group (p = 0.005). The agent-regime interaction was not significant (p = 0.443). Eleven participants (25%) with CARDT did not complete their treatment.

Conclusion: CARDT occurred more frequently with Benznidazole treatment, particularly with longer exposure despite the half-dose regimen. Clinicians should consider these differences when discussing treatment options with patients receiving nitro derivative agents.