Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis - EQUITY): study protocol for a randomised controlled trial
Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis - EQUITY): study protocol for a randomised controlled trial
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DOI：
10.1186/s13063-019-3423-3
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发表时间：
2019-07-15
期刊：
影响因子：
2.5
通讯作者：
Hernandez, Yolanda
中科院分区：
文献类型：
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作者：
Carlos Villar, Juan;Mauricio Herrera, Victor;Hernandez, Yolanda
苯并咪唑（benznidazole，BZN）和硝呋莫司（nifurtimox，NFX）是治疗克氏锥虫感染的有效药物。尽管如此，从随机试验的支持性数据是有限的，以BZN在南锥体国家的LatinAmerica.MethodsThe目标，这个随机化，隐蔽，盲目，平行组试验是通知锥虫的疗效和安全性NFX和它的等效性BZN在个人与T。克氏阳性血清学（TC+）。符合条件的个体是TC+，20- 65岁，没有明显的心肌病症状/体征或不受控制的风险因素，并且再感染的风险可以忽略不计。接受NFX、BZN或匹配安慰剂（2：2：1比例）的120天BID盲法治疗的个体（遵守10天安慰剂导入期）。四个活性药物组包括（1）随机分配的60天常规剂量（60 CD）方案（BZN 300 mg/天或NFX 480 mg/天，比例1：1），随后或之前进行60天安慰剂治疗，或（2）120天半剂量（120 HD）方案（BZN 150 mg/天或NFX 240 mg/天，比例1：1）。主要疗效结局是随机化后12- 18个月，最多3次聚合酶链反应（PCR）检测（1+PCR）中至少1次检测阳性的受试者比例。复合安全性结局包括中度至重度不良反应、一致的血液标志物异常或放弃治疗。哥伦比亚以外的试验（预计招募至少60%的参与者）是务实的;它可能是开放标签的，不包括所有治疗组，但必须遵守随机化和数据管理系统，并保证盲态疗效结局评价。我们的主要比较包括NFX组与安慰剂组（优效性）、NFX组与BZN组和60 CD组与120 HD组（非劣效性），并检验药物-剂量和组-区域相互作用。假设安慰剂组中1+PCR >= 75%，BZN治疗组中高达25%，NFX的绝对差异高达>= 25%，以声称其杀锥虫作用，每组60-80名参与者（至少300名来自哥伦比亚）来检验我们的假设（80-90%功效;单侧α水平1%）.DiscussionThe EQUITY试验将告知杀锥虫效果和硝基衍生物剂NFX和BZN的等效性，特别是在南锥体国家以外。其结果可能会挑战目前的建议，并为这些代理商的选择提供信息。registrationClinicalTrials.gov于2015年2月24日注册。
BackgroundEither benznidazole (BZN) or nifurtimox (NFX) is recommended as equivalent to treat Trypanosoma cruzi infection. Nonetheless, supportive data from randomised trials is limited to individuals treated with BZN in southern cone countries of Latin America.MethodsThe goal of this randomised, concealed, blind, parallel-group trial is to inform the trypanocidal efficacy and safety of NFX and its equivalence to BZN among individuals with T. cruzi positive serology (TC+). Eligible individuals are TC+, 20-65years old, with no apparent symptoms/signs or uncontrolled risk factors for cardiomyopathy and at negligible risk of re-infection. Consenting individuals (adherent to a 10-day placebo run-in phase) receive a 120-day BID blinded treatment with NFX, BZN or matching placebo (2:2:1 ratio). The four active medication arms include (1) a randomly allocated sequence of 60-day, conventional-dose (60CD) regimes (BZN 300mg/day or NFX 480mg/day, ratio 1:1), followed or preceded by a 60-day placebo treatment, or (2) 120-day half-dose (120HD) regimes (BZN 150mg/day or NFX 240mg/day, ratio 1:1). The primary efficacy outcome is the proportion of participants testing positive at least once for up to three polymerase chain reaction (PCR) assays (1+PCR) 12-18months after randomisation. A composite safety outcome includes moderate to severe adverse reactions, consistent blood marker abnormalities or treatment abandons. The trial outside Colombia (expected to recruit at least 60% of participants) is pragmatic; it may be open-label and not include all treatment groups, but it must adhere to the randomisation and data administration system and guarantee a blinded efficacy outcome evaluation. Our main comparisons include NFX groups with placebo (for superiority), NFX versus BZN groups and 60CD versus 120HD groups (for non-inferiority) and testing for the agent-dose and group-region interactions. Assuming a 1+PCR >= 75% in the placebo group, up to 25% among BZN-treated and an absolute difference of up to >= 25% with NFX to claim its trypanocidal effect, 60-80 participants per group (at least 300 from Colombia) are needed to test our hypotheses (80-90% power; one-sided alpha level 1%).DiscussionThe EQUITY trial will inform the trypanocidal effect and equivalence of nitroderivative agents NFX and BZN, particularly outside southern cone countries. Its results may challenge current recommendations and inform choices for these agents.Trial registrationClinicalTrials.gov, NCT02369978. Registered on 24 February 2015.