Short-course Benznidazole Treatment to Reduce Trypanosoma Cruzi Parasitic Load in Women of Reproductive Age: A Non-inferiority Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 87
- 试验地点
- 5
- 主要终点
- The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg
研究概览
简要总结
The investigators 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). The investigators 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%. The investigators are planning to enroll 600 T. cruzi seropositive women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Written informed consent from the mother.
- •T. cruzi seropositivity confirmed by at least two positive tests.
- •Live birth.
排除标准
- •Women residing outside of the provinces of Chaco, Santiago del Estero, or Tucumán.
- •Previous trypanocide treatment (BZN or nifurtimox).
- •Female sterilization; no intention to use modern contraception methods during treatment.
- •Positive pregnancy test.
- •History of severe alcohol abuse within two years; renal insufficiency.
研究组 & 干预措施
30/150mg
The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). ELEA laboratories will prepare the placebo oral tablets, which will be identical to the drug tablets in aspect and taste. The investigators will purchase the drug and placebo at full cost.
Interventions: The BZN short course low dose scheme will be 150 mg per day for 30 days. The drug will be administered orally in two doses per day: the short course treatment will start with the active drug and then placebo oral tablet; one 100 mg tablet and one placebo tablet in the morning and one 50 mg tablet and one placebo tablet in the evening for the first 30 days. The last 30 days will be two placebo tablets in the morning and the evening.
干预措施: Placebo Oral Tablet (Drug)
60/300mg
The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). The investigators will purchase the drug at full cost.
Interventions: The standard 60d course will be 300 mg per day, which is similar to the dose used in the second phase of the BENEFIT trial. The drug will be administered orally in two doses per day: the standard course will be one 100mg and one 50mg tablet in the morning and in the evening for 60 days.
干预措施: Benznidazole (Drug)
30/150mg
The investigators will use a preparation of benznidazole (BZN) that is commercially available in Argentina: Abarax® 100mg and 50mg tablets from ELEA laboratories (Buenos Aires, Argentina). ELEA laboratories will prepare the placebo oral tablets, which will be identical to the drug tablets in aspect and taste. The investigators will purchase the drug and placebo at full cost.
Interventions: The BZN short course low dose scheme will be 150 mg per day for 30 days. The drug will be administered orally in two doses per day: the short course treatment will start with the active drug and then placebo oral tablet; one 100 mg tablet and one placebo tablet in the morning and one 50 mg tablet and one placebo tablet in the evening for the first 30 days. The last 30 days will be two placebo tablets in the morning and the evening.
干预措施: Benznidazole (Drug)
结局指标
主要结局
The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg
时间窗: 10 months from the end of the 60d treatment
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.
Frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg
时间窗: 30 days for the 30d course arm, and 60 days for the 60d course arm
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.
Global PCR (Conventional PCR and Real-time Quantitative PCR) Immediately After the End of Treatment.
时间窗: Immediately after the end of treatment: 30 days for the 30-day arm, and 60 days for the 60-day arm.
Number of participants with at least one of the four conventional and/or one of the four quantitative PCR tests positive.
Global PCR (Conventional PCR and Real-time Quantitative PCR) at 10 Months After the End of the 60-day Treatment Period.
时间窗: 10 months after the end of the 60-day treatment period.
Number of participants with at least one of the four conventional and/or one of the four quantitative PCR tests positive.
次要结局
- The frequency of serious adverse events leading to treatment interruption of BZN 30d/150mg compared to 60d/300mg immediately after BZN 30d/150mg(60 days after treatment initiation)
- Serious Adverse Events and/or Any Adverse Event Leading to Treatment Discontinuation.(Randomization until last visit (10 months after the end of treatment or early termination).)
- Median Parasitic Load by qPCR Immediately After the End of Treatment in Detectable Samples.(Immediately after the end of treatment.)
- Median Parasitic Load by qPCR at 10 Months From the End of the 60-day Treatment Period in Detectable Samples(10 months from the end of the 60-day treatment period.)