Cardiovascular Health Investigation and Collaboration From Countries of America to Assess the Markers and Outcomes of Chagas Disease (CHICAMOCHA-3) - EQUITY (Equivalence of Usual Interventions for Trypanosomiasis)
试验速览
- 阶段
- 2 期
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Quantitative Polymerase Chain Reaction (qPCR) for Trypanosoma cruzi
研究概览
简要总结
This randomized, blind, parallel-group trial will evaluate the efficacy and safety of Nifurtimox (NFX) and Benznidazole (BZN), the two usual interventions to treat the parasite Trypanosoma cruzi.
The investigators will test whether NFX is an effective trypanocidal agent (by comparison with placebo) and equivalent to BZN (as active comparator) in terms of both parasite-related and safety outcomes.
Individuals found seropositive and without clinical signs of dilated cardiomyopathy will receive either of the active treatments or matching placebo. Participants allocated to NFX or BZN will receive either a 60-day (full-dose) or a 120-day (half-dose) active treatment, whereas the control group will receive placebo for 120 days. There will be thus four arms of active treatment (NFX60, NFX120, BZN60 and BZN120), and a fifth control arm receiving placebo (1:1:1:1:1 allocation ratio) where every participant in the trial will take 120 days of study drug (the groups receiving full-dose will complete a 120-day masked treatment with placebo).
The study plans to enroll 500 participants from Colombia (in two different geographical areas) and Argentina, in order to explore regional differences in the treatment effects.
详细描述
The specific aims of this multi-center randomized trial include:
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To evaluate the feasibility of conducting a multinational trial in terms of
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the ability to identify and recruit T. cruzi-infected individuals without clinical disease in a relatively short period
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the standardization of procedures to test the parasitic load using polymerase chain reaction (PCR)
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To evaluate, in the study population, the efficacy of a treatment with NFX using conventional (full) dose (8/mg/Kg/day) or half-dose for a variable duration (full-dose for 60 days versus half-dose for 120 days) in terms of the presence of positive PCR tests one year after treatment, as compared with placebo.
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To evaluate the equivalence (in terms of non-inferiority of its impact over the PCR testing) of two treatment schedules with NFX: a full-dose treatment for 60 days and a half-dose treatment for 120 days.
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To evaluate the equivalence of two treatment schedules with BZN: A conventional (full) dose of 5 mg/Kg/day) for 60 days, as compared with half-dose treatment for 120 days.
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To evaluate the equivalence of the treatment schedules with NFX as compared with those with BZN 5
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To evaluate the safety (in terms of reporting of mild symptoms, limitation of daily activities or hospitalizations, biochemical or blood abnormalities commonly reported by individuals taking these treatments) and adherence to the allocated treatments among individuals receiving NFX or BZN for varying duration and dose, as compared with placebo
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To explore differences in the impact of active treatments on the PCR among four subgroups of interest (geographical origin, T. cruzi discrete type unit found, parasitic load at baseline and age of participants).
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To explore, among individuals treated with placebo, the level of agreement in the tests of parasitic load at baseline and during the follow up.
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)
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Positive serology status to Trypanosoma cruzi
- •No clinical signs of dilated cardiomyopathy
排除标准
- •Unacceptable risk of re-infection, based on the investigators judgment
- •Previous treatment with NFX or BZN
- •History of peripheral neuropathy
- •Health condition limiting the mobility, cognitive function or life expectancy within two years of the enrollment visit
- •Pregnancy / Unwilling to use reliable contraceptive methods during childbearing age
研究组 & 干预措施
Nifurtimox (NFX)
60 days of active treatment with full-dose, or 120 days of active treatment with half-dose (allocation ratio 1:1). The 60-day group will receive active treatment in the first or second half of a 120-day treatment window, as per random allocation. The active treatment period will be followed/preceded by matching placebo (see placebo arm below)
干预措施: Nifurtimox (Drug)
Benznidazole (BZN)
60 days of active treatment with full-dose, or 120 days of active treatment with half-dose (allocation ratio 1:1). The 60-day group will receive active treatment in the first or second half of a 120-day treatment window, as per random allocation. The active treatment period will be followed/preceded by matching placebo (see placebo arm below)
干预措施: Benznidazole (Drug)
Placebo
120 days of treatment with matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Quantitative Polymerase Chain Reaction (qPCR) for Trypanosoma cruzi
时间窗: 12 - 18 months after starting therapy
Proportion of participants with at least one out of three positive tests (performed at least one week apart from each other)
次要结局
- T. cruzi positive serology status(12 months after starting therapy)
- Mean change in T. cruzi antibody titers(12 months after starting therapy)
研究者
Juan Carlos Villar, MD, PhD
Professor, Department of Medicine
Universidad Autónoma de Bucaramanga