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青蒿琥酯与奎宁治疗重症恶性疟的随机对照试验

Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.

作者信息

Dondorp Arjen, Nosten François, Stepniewska Kasia, Day Nick, White Nick

机构信息

Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

出版信息

Lancet. 2005;366(9487):717-25. doi: 10.1016/S0140-6736(05)67176-0.

Abstract

BACKGROUND

In the treatment of severe malaria, intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance, is safer, and is simpler to administer, but whether it can reduce mortality is uncertain.

METHODS

We did an open-label randomised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh, India, Indonesia, and Myanmar. We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus (n=730) at 0, 12, and 24 h, and then daily, or intravenous quinine (20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2-8 h three times a day; n=731). Oral medication was substituted when possible to complete treatment. Our primary endpoint was death from severe malaria, and analysis was by intention to treat.

FINDINGS

We assessed all patients randomised for the primary endpoint. Mortality in artesunate recipients was 15% (107 of 730) compared with 22% (164 of 731) in quinine recipients; an absolute reduction of 34.7% (95% CI 18.5-47.6%; p=0.0002). Treatment with artesunate was well tolerated, whereas quinine was associated with hypoglycaemia (relative risk 3.2, 1.3-7.8; p=0.009).

INTERPRETATION

Artesunate should become the treatment of choice for severe falciparum malaria in adults.

摘要

背景

在重症疟疾的治疗中,就疟原虫清除而言,静脉注射青蒿琥酯比静脉注射奎宁起效更快,更安全,给药也更简便,但它能否降低死亡率尚不确定。

方法

我们在孟加拉国、印度、印度尼西亚和缅甸对因重症恶性疟原虫疟疾入院的患者进行了一项开放标签随机对照试验。我们将患者分为两组,一组静脉注射青蒿琥酯,剂量为2.4毫克/千克体重,分别在0、12和24小时推注一次(n = 730),然后每日注射一次;另一组静脉注射奎宁(负荷剂量为20毫克盐/千克,4小时内输注完毕,然后每天三次,每次10毫克/千克,2 - 8小时内输注完毕;n = 731)。尽可能用口服药物替代以完成治疗。我们的主要终点是重症疟疾导致的死亡,分析采用意向性分析。

结果

我们评估了所有随机分组以确定主要终点的患者。接受青蒿琥酯治疗的患者死亡率为15%(730例中的107例),而接受奎宁治疗的患者死亡率为22%(731例中的164例);绝对降低率为34.7%(95%置信区间18.5 - 47.6%;p = 0.0002)。青蒿琥酯治疗耐受性良好,而奎宁与低血糖有关(相对风险3.2,1.3 - 7.8;p = 0.009)。

解读

青蒿琥酯应成为成人重症恶性疟原虫疟疾的首选治疗药物。

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