Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria:: A randomized controlled trial
Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria:: A randomized controlled trial
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DOI：
10.1086/430309
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发表时间：
2005-06-15
影响因子：
11.8
通讯作者：
Kremsner, PG
中科院分区：
文献类型：
--
作者：
Ramharter, M;Oyakhirome, S;Kremsner, PG
背景青蒿素类复方药物是非洲防治抗药性疟疾的主要手段。目前可用的包括青蒿素的抗疟复方药物在药代动力学上是无与伦比的，因此有可能增加疟疾传播率高的地区选择抗药突变体的风险。我们测试了以青蒿素为基础的联合疗法的潜在价值，其消除半衰期较短，用于治疗撒哈拉以南非洲地区单纯恶性疟原虫疟疾。我们进行了一项开放、随机、对照的临床试验，以评估每日两次口服青蒿琥酯-克林霉素治疗3天的疗效和耐受性（青蒿琥酯，2毫克/公斤，克林霉素，7毫克/公斤，每剂量），与标准的奎宁-克林霉素方案给予每日两次，共3天（奎宁，15毫克/公斤，克林霉素，7毫克/公斤，每剂），用于治疗100名3 - 12岁的加蓬儿童的无并发症恶性疟疾。研究的主要终点是符合方案人群的聚合酶链反应校正治愈率。在随访第28天的治愈率的符合方案分析中，青蒿琥酯-克林霉素的活性与奎宁-克林霉素的活性相当（87%对94%）。未报告严重不良事件，耐受性良好，两组相似。青蒿琥酯-克林霉素组的退热时间和寄生虫清除时间显著缩短。青蒿琥酯-克林霉素和其他血浆半衰期短的青蒿素类复方制剂值得进一步关注，以便在疟疾传播率高的地区使用。
Background. Artemisinin-based drug combinations are the mainstay in the fight against drug-resistant malaria in Africa. Currently available antimalarial drug combinations that include artemisinins are pharmacokinetically unmatched and are therefore potentially increasing the risk of selection of resistant mutants in areas in which the rate of transmission of malaria is high. We tested the potential value of artemisinin-based combination therapy with a short elimination half-life for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa.Methods. We conducted an open-label, randomized, controlled clinical trial to evaluate the efficacy and tolerability of oral artesunate-clindamycin therapy given twice daily for 3 days ( artesunate, 2 mg/kg, and clindamycin, 7 mg/ kg, per dose), compared with a standard quinine-clindamycin regimen given twice daily for 3 days ( quinine, 15 mg/ kg, and clindamycin, 7 mg/ kg, per dose), for the treatment of uncomplicated falciparum malaria in 100 Gabonese children aged 3 - 12 years. The primary end point of the study was the polymerase chain reaction corrected cure rate for the per-protocol population.Results. The activity of artesunate-clindamycin was comparable to that of quinine-clindamycin in the perprotocol analysis of cure rates at day 28 of follow-up (87% versus 94%). No serious adverse events were reported, and tolerability was good and was similar in both groups. Times to clearance of fever and clearance of parasites were significantly shorter in the artesunate-clindamycin group.Conclusions. Artesunate-clindamycin and other matching artemisinin-based combinations with a short plasma half-life merit further attention for use in regions in which the rate of transmission of malaria is high.