苯硝唑和泊沙康唑消除无症状 T. cruzi 携带者寄生虫：STOP-CHAGAS 试验。
Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers: The STOP-CHAGAS Trial.
机构信息
McMaster University, Population Health Research Institute, Hamilton, Ontario, Canada.
Merck Sharp and Dohme Corporation, Kenilworth, New Jersey.
出版信息
J Am Coll Cardiol. 2017 Feb 28;69(8):939-947. doi: 10.1016/j.jacc.2016.12.023.
BACKGROUND
Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers.
OBJECTIVES
The purpose of this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers.
METHODS
A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days.
RESULTS
Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole.
CONCLUSIONS
Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480).
背景
苄硝唑被推荐用于治疗恰加斯病感染。尚未在克氏锥虫携带者中测试苄硝唑和泊沙康唑联合治疗的效果。
目的
本研究旨在确定泊沙康唑单药治疗或联合苄硝唑治疗是否优于苄硝唑单药治疗，通过实时聚合酶链反应（RT-PCR）在无症状的恰加斯病携带者中消除克氏锥虫寄生虫。
方法
在拉丁美洲和西班牙的 120 名受试者中进行了一项前瞻性、多中心、随机安慰剂对照研究，他们被随机分为 4 组：泊沙康唑 400 mg，每日两次（bid）；苄硝唑 200 mg+安慰剂 bid；苄硝唑 200 mg bid+泊沙康唑 400 mg bid；或安慰剂 10 mg bid。通过 RT-PCR 在 30、60、90、120、150、180 和 360 天检测克氏锥虫脱氧核糖核酸。主要疗效终点是第 180 天持续阴性 RT-PCR 的受试者比例；次要终点是 360 天的阴性 RT-PCR。
结果
接受泊沙康唑治疗的患者中只有 13.3%，接受安慰剂治疗的患者中只有 10%达到了主要终点，而接受苄硝唑+泊沙康唑治疗的患者中则有 80%，接受苄硝唑单药治疗的患者中则有 86.7%（p<0.0001 对比泊沙康唑/安慰剂）。泊沙康唑单药治疗或联合苄硝唑治疗在治疗期间均实现了较高的 RT-PCR 转化率（30 天，93.3%和 88.9%，60 天，90%和 92.3%），与苄硝唑（89.7%和 89.3%）相似；均优于安慰剂或泊沙康唑（10%和 16.7%，p<0.0001）。但在 360 天观察时并未观察到这一点；苄硝唑+泊沙康唑和苄硝唑单药治疗（均为 96%）对比安慰剂（17%）和泊沙康唑（16%，p<0.0001）。严重不良事件很少见（6 例），发生在接受苄硝唑治疗的患者中。共有 19 名（31.7%）接受苄硝唑单药或联合泊沙康唑治疗的患者永久停药。
结论
泊沙康唑在治疗期间表现出杀锥虫活性，但在无症状克氏锥虫携带者中长期无效。苄硝唑单药治疗优于泊沙康唑，在 1 年内持续保持较高的 RT-PCR 转化率。副作用导致 32%的患者停药。与苄硝唑单药治疗相比，联合治疗并未显示出任何优势。
Zotero 插件