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.项目摘要/摘要 恰加斯病，或美国锥虫病，是由寄生虫克氏锥虫引起的。这是一名少校 美洲心脏病的起因。据估计，目前有600万人感染，其中包括1人 100万育龄妇女。母亲可以在怀孕期间将克氏锥虫传播给她们的婴儿，并且 受感染的婴儿在以后的生活中有患慢性恰加斯病的风险。 回溯性观察研究表明，在年轻时接受治疗的妇女在以下情况下不会传播克氏锥虫 晚年怀孕的。寄生虫载量水平是先天传播的已知危险因素。苯硝唑 (BZN)是产前治疗的首选药物，以减少寄生虫负荷。与治疗相关的恐惧 副作用限制了使用BZN 300 mg/d的标准60天治疗的实施 产后期血清阳性的妇女，以防止在未来怀孕期间传播。一小段和 小剂量补肾宁治疗可减少主要副作用，提高依从性，但其降低T. 克鲁兹的寄生负荷与标准的60天疗程相比尚未确立。 我们建议进行一项双盲、非劣势的随机对照试验，比较短短30个月的 每日服用BZN 150 mg(30d/150 mg)与60天服用BZN 300 mg/天(60d/300 mg)。 我们将招募未经治疗的克雷伯氏旋毛虫血清阳性妇女，并在产后活产。 在阿根廷，在产后六个月对他们进行随机化，并跟进以下具体目标： 具体目标1：观察BZN 30d/150 mg与60d/300 mg孕前治疗的效果 用聚合酶链式反应阳性率(主要结果)和实时定量检测寄生虫量 治疗后即刻(特异靶1a)和10个月(特异靶1b)。 假设1a：聚合酶链式反应阳性的频率和感染后立即用定量聚合酶链式反应测量的寄生虫量 BZN 30d/150 mg将不比BZN差(PCR的非劣势[NI]差值：10%的绝对差值) 60d/300 mg。 假设1b：BZN后10个月用定量聚合酶链式反应检测阳性聚合酶链式反应的频率和寄生虫载量 30d/150 mg将不低于BZN 60d/300 mg(聚合酶链式反应的NI边际：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 30d/150 mg，60d/300 mg。 假设2：严重不良事件导致治疗中断的频率将降低50% BZN 30d/150 mg组优于BZN 60d/300 mg组。 计划在四家医院进行为期24个月的招募，2015年将有23,436名产妇出生，T。 CRUZI阳性者占1.5%至4.8%。我们计划招收600名血清阳性克雷伯氏杆菌 女人。

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