Priotto Gerardo, Fogg Carole, Balasegaram Manica, Erphas Olema, Louga Albino, Checchi Francesco, Ghabri Salah, Piola Patrice
PLoS Clin Trials. 2006 Dec 8;1(8):e39. doi: 10.1371/journal.pctr.0010039.
Our objective was to compare the efficacy and safety of three drug combinations for the treatment of late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense.
This trial was a randomized, open-label, active control, parallel clinical trial comparing three arms.
The study took place at the Sleeping Sickness Treatment Center run by Médecins Sans Frontières at Omugo, Arua District, Uganda
Stage 2 patients diagnosed in Northern Uganda were screened for inclusion and a total of 54 selected.
Three drug combinations were given to randomly assigned patients: melarsoprol-nifurtimox (M+N), melarsoprol-eflornithine (M+E), and nifurtimox-eflornithine (N+E). Dosages were uniform: intravenous (IV) melarsoprol 1.8 mg/kg/d, daily for 10 d; IV eflornithine 400 mg/kg/d, every 6 h for 7 d; oral nifurtimox 15 (adults) or 20 (children <15 y) mg/kg/d, every 8 h for 10 d. Patients were followed up for 24 mo.
Outcomes were cure rates and adverse events attributable to treatment.
Randomization was performed on 54 patients before enrollment was suspended due to unacceptable toxicity in one of the three arms. Cure rates obtained with the intention to treat analysis were M+N 44.4%, M+E 78.9%, and N+E 94.1%, and were significantly higher with N+E (p = 0.003) and M+E (p = 0.045) than with M+N. Adverse events were less frequent and less severe with N+E, resulting in fewer treatment interruptions and no fatalities. Four patients died who were taking melarsoprol-nifurtimox and one who was taking melarsoprol-eflornithine.
The N+E combination appears to be a promising first-line therapy that may improve treatment of sleeping sickness, although the results from this interrupted study do not permit conclusive interpretations. Larger studies are needed to continue the evaluation of this drug combination in the treatment of T. b. gambiense sleeping sickness.
我们的目的是比较三种药物组合治疗由布氏冈比亚锥虫引起的晚期人类非洲锥虫病的疗效和安全性。
本试验是一项随机、开放标签、活性对照、平行的临床试验，比较三个治疗组。
该研究在乌干达阿鲁阿区奥穆戈无国界医生组织运营的昏睡病治疗中心进行。
对在乌干达北部诊断出的2期患者进行筛选以纳入研究，共选择了54名患者。
将三种药物组合随机分配给患者：美拉胂醇-硝呋莫司（M+N）、美拉胂醇-依氟鸟氨酸（M+E）和硝呋莫司-依氟鸟氨酸（N+E）。剂量统一：静脉注射美拉胂醇1.8mg/kg/天，共10天；静脉注射依氟鸟氨酸400mg/kg/天，每6小时一次，共7天；口服硝呋莫司15（成人）或20（15岁以下儿童）mg/kg/天，每8小时一次，共10天。对患者进行24个月的随访。
观察指标为治愈率和治疗相关不良事件。
在因三个治疗组之一出现不可接受的毒性而暂停入组前，对54名患者进行了随机分组。意向性分析得到的治愈率为：M+N组44.4%，M+E组78.9%，N+E组94.1%，N+E组（p=0.003）和M+E组（p=0.045）的治愈率显著高于M+N组。N+E组的不良事件发生频率更低、严重程度更轻，导致治疗中断更少且无死亡病例。服用美拉胂醇-硝呋莫司的4名患者死亡，服用美拉胂醇-依氟鸟氨酸的1名患者死亡。
N+E组合似乎是一种有前景的一线治疗方法，可能改善昏睡病的治疗，尽管这项中断的研究结果不允许得出确定性的解释。需要进行更大规模的研究，以继续评估这种药物组合治疗布氏冈比亚锥虫昏睡病的效果。
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