Short-course Benznidazole Treatment to Reduce Trypanosoma cruzi Parasitic Load in Women of Reproductive Age: A Non-inferiorityRandomized Controlled Trial

7.项目概要/摘要 查加斯病，或美洲锥虫病，是由寄生虫克氏锥虫引起的。它是一个主要 是美洲心脏病的主要原因据估计，目前有600万人受到感染，其中包括一名 百万育龄妇女。母亲可以传播T。cruzi给她们的孩子在怀孕期间， 受感染的婴儿在以后的生活中有患慢性恰加斯病的危险。 回顾性观察研究表明，年轻时接受治疗的女性不会传播T。克鲁齐当 晚年怀孕。寄生负载水平是先天性传播的已知风险因素。苄硝唑 (BZN)是减少寄生虫负荷的孕前治疗的首选药物。治疗相关的恐惧 副作用限制了用BZN 300 mg/天的T进行标准60天治疗的实施。cruzi 在产后期间对血清反应呈阳性的妇女进行监测，以防止在今后怀孕期间传播。一个简短而 小剂量BZN治疗可减少主要副作用，提高依从性，但降低T. cruzi寄生负荷与标准60天疗程的比较尚未确定。 我们建议进行一项双盲、非劣效性随机对照试验， BZN 150 mg/d治疗30 d/150 mg，BZN 300 mg/d治疗60 d/300 mg。 我们将招募以前没有治疗过的T。产后活产的克氏血清反应阳性妇女 在阿根廷，在产后六个月时对她们进行随机分组，并按照以下具体目标进行随访： 具体目的1：测量BZN 30 d/150 mg与60 d/300 mg孕前治疗相比的效果 通过阳性PCR频率（主要结果）和实时定量 PCR（qPCR），治疗后立即（特异性目的1a）和10个月（特异性目的1b）。 假设1a：阳性PCR的频率和在接种后立即通过qPCR测量的寄生虫负荷 BZN 30 d/150 mg非劣效于BZN（PCR的非劣效性[NI]界值：10%绝对差异） 60d/300mg。 假设1b：BZN后10个月通过qPCR测量的阳性PCR频率和寄生虫负荷 30天/150 mg非劣效于（PCR的NI界值：9%绝对差异）BZN 60天/300 mg。 具体目的2：测量导致BZN治疗中断的严重不良事件的频率 30 d/150 mg与60 d/300 mg相比。 假设2：导致治疗中断的严重不良事件的频率将降低50%， BZN 30 d/150 mg组显著高于BZN 60 d/300 mg组。 计划在四家医院进行为期24个月的招募，2015年有23,436例分娩，T。 克氏血清反应阳性的妇女占1.5%至4.8%。我们计划招募600名T。克氏血清阳性 妇女

7. Project Summary/Abstract Chagas disease, or American trypanosomiasis, is caused by the parasite Trypanosoma cruzi. It is a major cause of cardiac disease in the Americas. An estimated six million persons are currently infected, including one million women of reproductive age. Mothers can transmit T. cruzi to their babies during pregnancy, and infected babies are at risk of developing chronic Chagas disease later in life. Retrospective observational studies suggest that women treated at a young age do not transmit T. cruzi when pregnant later in life. The level of parasitic load is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment-related side effects limits the implementation of the standard 60-day treatment with BZN 300 mg/day of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60-day course is not yet established. We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short 30- day treatment with BZN 150mg/day (30d/150mg) vs. a 60-day treatment with BZN 300 mg/day (60d/300mg). We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at six months postpartum, and follow them up with the following specific aims: Specific Aim 1: To measure the effect of BZN 30d/150mg compared to 60d/300mg preconceptional treatment on parasitic load measured by the frequency of positive PCR (primary outcome) and by real-time quantitative PCR (qPCR), immediately (Specific Aim 1a) and 10 months (Specific Aim 1b) after treatment. Hypothesis 1a: The frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg will be non-inferior (Non Inferiority [NI] margin for PCR: 10% absolute difference) to BZN 60d/300mg. Hypothesis 1b: The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg will be non-inferior (NI margin for PCR: 9% absolute difference) to BZN 60d/300mg. Specific Aim 2: To measure the frequency of serious adverse events leading to treatment interruption of BZN 30d/150mg compared to 60d/300mg. Hypothesis 2: The frequency of serious adverse events leading to treatment interruption will be 50% lower with BZN 30d/150mg than with BZN 60d/300mg. A 24-month recruitment period is planned in four hospitals with 23,436 deliveries in 2015 and frequencies of T. cruzi seropositive women varying from 1.5% to 4.8%. We are planning to enroll 600 T. cruzi seropositive women.