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

短期苯硝唑治疗减少育龄妇女克氏锥虫寄生负荷：非劣效性随机对照试验

• 批准号: 10429944
• 负责人: PIERRE BUEKENS
• 金额: $ 56.83万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10429944
• 关键词: Adverse event; Aftercare; Age; Americas; Animals; Argentina; Argentine; Benznidazole; Chagas Disease; Chronic; Clinical Trials; Dose; Double-Blind Method; Drug Kinetics; Enrollment; Frequencies; Fright; Future; Guidelines; Heart Diseases; Hospitals; Infection; Interruption; Life; Live Birth; Measures; Mothers; Observational Study; Overdose; Parasites; Patients; Persons; Pharmaceutical Preparations; Placebos; Population; Postpartum Period; Pregnancy; Public Health; Randomized; Randomized Controlled Trials; Research; Risk; Risk Factors; Serious Adverse Event; Source; Testing; Time; Treatment Failure; Treatment Side Effects; Trypanosoma cruzi; United States; Woman; chagasic cardiomyopathy; congenital infection; cost; placebo group; pregnant; prevent; primary outcome; recruit; reproductive; seropositive; side effect; transmission process; treatment duration; trial comparing

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.

7. 项目总结/摘要 恰加斯病或美洲锥虫病是由寄生虫克氏锥虫引起的。这是一个主要的 美洲心脏病的病因。目前估计有 600 万人被感染，其中包括 1 人 百万育龄妇女。母亲可以在怀孕期间将克氏锥虫传染给婴儿，并且 受感染的婴儿在以后的生活中面临患慢性恰加斯病的风险。 回顾性观察研究表明，年轻时接受治疗的女性在以下情况下不会传播克氏锥虫： 以后怀孕。寄生负荷水平是先天性传播的已知危险因素。苯并硝唑 (BZN) 是孕前治疗减少寄生虫负荷的首选药物。对治疗相关的恐惧 副作用限制了用 BZN 300 毫克/天克氏锥虫进行标准 60 天治疗的实施 产后血清反应呈阳性的妇女，以防止在未来怀孕时传播。一个简短的和 低剂量 BZN 治疗可能会减少主要副作用并提高依从性，但其减少 T. 与标准 60 天课程相比，cruzi 寄生负载尚未确定。 我们建议进行一项双盲、非劣效性随机对照试验，比较一项简短的 30- BZN 150mg/天的日治疗（30d/150mg）与 BZN 300mg/天的 60 天治疗（60d/300mg）。 我们将招募之前未接受过治疗的产后活产的克氏锥虫血清阳性女性 在阿根廷，在产后六个月对她们进行随机分组，并按照以下具体目标进行跟踪： 具体目标 1：比较 BZN 30d/150mg 与 60d/300mg 孕前治疗的效果 通过阳性 PCR 频率（主要结果）和实时定量测量寄生负载 治疗后立即（具体目标 1a）和 10 个月（具体目标 1b）进行 PCR (qPCR)。 假设 1a：阳性 PCR 的频率和 PCR 后立即通过 qPCR 测量的寄生负荷 BZN 30d/150mg 将不劣于 BZN（PCR 的非劣效 [NI] 裕度：10% 绝对差异） 60天/300毫克。 假设 1b：BZN 后 10 个月的阳性 PCR 频率和 qPCR 测量的寄生负荷 30d/150mg 不劣于 BZN 60d/300mg（PCR NI 裕度：9% 绝对差异）。 具体目标 2：测量导致 BZN 治疗中断的严重不良事件的频率 30 天/150 毫克与 60 天/300 毫克相比。 假设 2：导致治疗中断的严重不良事件的频率将降低 50% BZN 30d/150mg 与 BZN 60d/300mg 相比。 四家医院计划进行为期 24 个月的招募期，2015 年分娩次数为 23,436 例，T. 克鲁兹血清阳性女性的比例从 1.5% 到 4.8% 不等。我们计划招募 600 只血清呈阳性的克氏锥虫 女性。

项目成果

Including unpublished surveys in reviews on Chagas disease in Mexico.

• DOI: 10.1186/s40985-020-00140-7
• 发表时间: 2020-11-11
• 期刊: Public health reviews
• 影响因子: 5.5
• 作者: Buekens P;López-Cárdenas J;Dumonteil E;Padilla-Raygoza N
• 通讯作者: Padilla-Raygoza N

COVID-19: Implications for People with Chagas Disease.

• DOI: 10.5334/gh.891
• 发表时间: 2020-10-13
• 期刊: Global heart
• 影响因子: 3.7
• 作者: Zaidel EJ;Forsyth CJ;Novick G;Marcus R;Ribeiro ALP;Pinazo MJ;Morillo CA;Echeverría LE;Shikanai-Yasuda MA;Buekens P;Perel P;Meymandi SK;Ralston K;Pinto F;Sosa-Estani S
• 通讯作者: Sosa-Estani S