Villar Juan Carlos, Saavedra María Fernanda, Bermúdez Pablo Andrés, Herrera Eliana Váquiro, Vásquez Skarlet Marcell, Arango Helena, Camacho Antonia, Olivera Mario Javier
Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia.
Centro de Investigaciones, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia.
Trop Med Int Health. 2025 Jul;30(7):673-684. doi: 10.1111/tmi.14123. Epub 2025 May 19.
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.
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.
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.
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.
在一项随机安慰剂对照试验中，确定使用苯硝唑治疗期间的皮肤不良反应（CARDT）是否与硝呋替莫一样常见，以及治疗剂量和疗程是否会改变该频率。
我们开展了EQUITY试验（NCT02369978），将无明显临床疾病的克氏锥虫血清阳性成人随机分配接受为期120天的苯硝唑、硝呋替莫或安慰剂盲法治疗（比例为2:2:1）。积极治疗组包括60天常规剂量（60CD）方案（苯硝唑300mg/天或硝呋替莫480mg/天，前后各加60天安慰剂）或120天半剂量（120HD）方案（苯硝唑150mg/天或硝呋替莫240mg/天）。在随访期间，CARDT经盲法判定为中度至重度。
在307名参与者中，接受积极治疗的246人中有42例CARDT（17.1%，95%置信区间[CI]12.6 - 22.4），而接受安慰剂的61名参与者中有2例CARDT（3.3%，9%CI 0.0 - 11.3）。在接受苯硝唑治疗的122名患者中，有31例CARDT（25.4%，包括8例重度），而在接受硝呋替莫治疗的124名个体中有11例CARDT（8.9%，包括4例重度）（p < 0.001）。在分配到120HD方案的125名参与者中，有26例CARDT（20.8%，包括6例重度），而60CD组的121名中有16例CARDT（13.2%，包括6例重度）（p = 0.005）。药物 - 方案交互作用不显著（p = 0.443）。11名有CARDT的参与者（25%）未完成治疗疗程。
苯硝唑治疗时CARDT发生更频繁，尤其是尽管采用了半剂量方案但暴露时间更长时。临床医生在与接受硝基衍生物药物治疗的患者讨论治疗方案时应考虑这些差异。
