Institut für Tropenmedizin, Universität Tübingen, Germany.
J Infect Dis. 2012 Jan 15;205(2):312-9. doi: 10.1093/infdis/jir724. Epub 2011 Dec 15.
We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria.
This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed.
In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008).
Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children.
NCT00522132.
我们比较了经验衍生的常规方案与重症疟疾中简化的青蒿琥酯静脉注射方案。
这是一项随机、双盲、安慰剂对照比较，旨在评估简化的 3 剂方案（分别在 0、24 和 48 小时给予）与传统的 5 剂方案（分别在 0、12、24、48 和 72 小时给予）在患有恶性疟原虫疟疾的非洲儿童中的非劣效性，预设差值为 0.2。每组青蒿琥酯的总剂量为 12 mg/kg。主要终点是 24 小时时清除≥99%入院寄生虫血症的儿童比例。还分析了安全性数据、次要疗效终点和药代动力学。
在 171 名儿童（按方案）中，3 剂组有 78%（95%置信区间[CI]，69%-87%）的患儿在治疗开始后 24 小时达到≥99%的寄生虫清除率，而接受常规方案的患儿有 85%（95% CI，77%-93%）（治疗差异，-7.2%；95% CI，-18.9%至 4.4%）。接受高剂量 3 剂方案的儿童中双氢青蒿素清除速度略慢（对于 13 公斤的儿童，7.4 升/小时对 8.8 升/小时；P<0.008）。
药效动力学分析表明，3 剂青蒿琥酯治疗儿童重症疟疾并不劣于 5 剂。
NCT00522132。
