Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.
Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.
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DOI：
10.1016/s0140-6736(08)61734-1
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发表时间：
2009-02-14
期刊：
影响因子：
168.9
通讯作者：
White, N. J.
中科院分区：
文献类型：
--
作者：
Gomes, M. F.;Faiz, M. A.;Gyapong, J. O.;Warsame, M.;Agbenyega, T.;Babiker, A.;Baiden, F.;Yunus, E. B.;Binka, F.;Clerk, C.;Folb, P.;Hassan, R.;Hossain, M. A.;Kimbute, O.;Kitua, A.;Krishna, S.;Makasi, C.;Mensah, N.;Mrango, Z.;Olliaro, P.;Peto, R.;Peto, T. J.;Rahman, M. R.;Ribeiro, I.;Samad, R.;White, N. J.
大多数疟疾死亡发生在农村地区。从疾病到死亡的快速发展可以通过及时有效的药物治疗来中断。抗疟疾治疗不能挽救绝症患者，但如果早期给予可能有效。如果不能口服治疗的患者距离注射设施有几个小时的路程，可以在转诊前给予直肠青蒿琥酯，并迅速对寄生虫起作用。我们调查了这种干预是否降低了死亡率和永久性残疾。在孟加拉国、加纳和坦桑尼亚，无法口服治疗的疑似严重疟疾患者被随机分配到一个青蒿琥酯栓剂（n=8954）或安慰剂栓剂（n=8872），服用下一个编号的盒子，然后转诊到可以注射的诊所。随机分组前接受抗疟药注射或血涂片阴性的患者被排除，留下12068例患者（青蒿琥酯6072例，安慰剂5996例）进行分析。 主要终点是7-30天后评估的死亡率和定期重新评估的永久性残疾。所有研究者均对分组设盲。该研究在所有三个国家注册，编号为ISRCTN 83979018、46343627和76987662。青蒿琥酯组6072例中有154例死亡，安慰剂组5996例中有177例死亡（2.5% vs 3.0%，p= 0.1）。2例与13例（0.03%与0.22%，p= 0.0020）永久性残疾;总死亡或残疾：156例与190例（2.6%与3.2%，p= 0.0484）。早期死亡率没有降低（6 h内死亡56例vs 51例;中位数为2 h）。在6小时内（中位数3小时）到达诊所的患者中，转诊前青蒿琥酯对6小时后死亡或永久性残疾无显著影响（71/4450 [1.6%] vs 82/4426 [1.9%]，风险比0.86 [95%CI 0.63 - 1.18]，p= 0.35）。然而，在超过6小时后仍不在诊所的患者中，超过15小时后仍有一半患者不在诊所，转诊前直肠青蒿琥酯显著降低了死亡或永久性残疾（29/1566 [1.9%] vs 57/1519 [3.8%]，风险比0.49 [95%CI 0.32 - 0.77]，p= 0.0013）。如果严重疟疾患者无法口服治疗，注射需要几个小时，在转诊时服用一粒廉价的青蒿琥酯栓剂可大大降低死亡或永久残疾的风险。儿童基金会/开发计划署/世界银行热带病研究和训练特别方案;卫生组织全球疟疾方案;萨尔家庭基金会;欧洲联盟（QLRT-2000-01430）;联合王国医学研究理事会;美援署;爱尔兰援助署;卡罗林斯卡医学院;牛津大学临床试验服务股。
Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7–30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2·5% vs 3·0%, p=0·1). Two versus 13 (0·03% vs 0·22%, p=0·0020) were permanently disabled; total dead or disabled: 156 versus 190 (2·6% vs 3·2%, p=0·0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1·6%] vs 82/4426 [1·9%], risk ratio 0·86 [95% CI 0·63–1·18], p=0·35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1·9%] vs 57/1519 [3·8%], risk ratio 0·49 [95% CI 0·32–0·77], p=0·0013). If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).