New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: a Pilot Short-Term Follow-Up Study with Adult Patients
New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: a Pilot Short-Term Follow-Up Study with Adult Patients
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DOI：
10.1128/aac.00745-15
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发表时间：
2016-02-01
影响因子：
4.9
通讯作者：
Viottia, Rodolfo
中科院分区：
文献类型：
--
作者：
Gabriela Alvarez, Maria;Hernandez, Yolanda;Viottia, Rodolfo
临床上有必要测试新的苯硝唑给药方案，这些方案预计至少与目前的治疗方案一样有效，但更安全。本研究评估了一种新的苯硝唑给药方案，用于慢性恰加斯病患者。设计了一项试验性研究，苯硝唑的间歇剂量为5 mg/kg/d，每5天分两次每日给药，共60天。治疗结束前和治疗后1周定量聚合酶链式反应(QPCR)结果的比较为疗效的主要标准。安全性通过停药率和不良反应的严重程度进行评估。对20名患者进行了安全性分析，同时对其中17名患者进行了qPCR检测。平均年龄为43+/-7.9岁；55%为女性。65%的受试者在治疗前显示出可检测到的qPCR结果，每毫升血液的寄生虫当量(PAR)分别为1.45(0.63至2.81)和2.1(1.18至2.78)。Eq/ml)，分别为动塑性DNA(KDNA)和核重复序列卫星DNA(SatDNA)qPCR。1例患者在治疗结束时可检测到聚合酶链式反应(1/17)，治疗失败率为6%，而治疗前为11/17(65%)(P=0.01)。10/20(50%)患者出现不良反应，但仅有1例暂停治疗。8名患者表现出轻微的不良反应，而2名患者观察到中度反应并伴有肝酶升高。这项初步研究的主要成果是有希望的低治疗悬浮率。间歇应用苯硝唑是一种新的潜在的治疗方案，其疗效有待于治疗后的长期评估来证实。
There is a clinical need to test new schemes of benznidazole administration that are expected to be at least as effective as the current therapeutic scheme but safer. This study assessed a new scheme of benznidazole administration in chronic Chagas disease patients. A pilot study with intermittent doses of benznidazole at 5 mg/kg/day in two daily doses every 5 days for a total of 60 days was designed. The main criterion of response was the comparison of quantitative PCR (qPCR) findings prior to and 1 week after the end of treatment. The safety profile was assessed by the rate of suspensions and severity of adverse effects. Twenty patients were analyzed for safety, while qPCR was tested for 17 of them. The average age was 43 +/- 7.9 years; 55% were female. Sixty-five percent of treated subjects showed detectable qPCR results prior to treatment of 1.45 (0.63 to 2.81) and 2.1 (1.18 to 2.78) parasitic equivalents per milliliter of blood (par. eq/ml) for kinetoplastic DNA (kDNA) qPCR and nuclear repetitive sequence satellite DNA (SatDNA) qPCR, respectively. One patient showed detectable PCR at the end of treatment (1/17), corresponding to 6% treatment failure, compared with 11/17 (65%) patients pretreatment (P = 0.01). Adverse effects were present in 10/20 (50%) patients, but in only one case was treatment suspended. Eight patients showed mild adverse effects, whereas moderate reactions with increased liver enzymes were observed in two patients. The main accomplishment of this pilot study is the promising low rate of treatment suspension. Intermittent administration of benznidazole emerges a new potential therapeutic scheme, the efficacy of which should be confirmed by long-term assessment posttreatment.