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Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial.
The Lancet ( IF 168.9 ) Pub Date : 2019-07-18 , DOI: 10.1016/s0140-6736(19)31285-1
Walter R J Taylor 1 , Kamala Thriemer 2 , Lorenz von Seidlein 3 , Prayoon Yuentrakul 1 , Thanawat Assawariyathipat 1 , Ashenafi Assefa 4 , Sarah Auburn 2 , Krisin Chand 5 , Nguyen Hoang Chau 6 , Phaik Yeong Cheah 1 , Le Thanh Dong 7 , Mehul Dhorda 8 , Tamiru Shibru Degaga 9 , Angela Devine 10 , Lenny L Ekawati 5 , Fahmi Fahmi 11 , Asrat Hailu 12 , Mohammad Anwar Hasanzai 13 , Tran Tinh Hien 14 , Htee Khu 1 , Benedikt Ley 2 , Yoel Lubell 1 , Jutta Marfurt 2 , Hussein Mohammad 4 , Kerryn A Moore 15 , Mohammad Nader Naddim 13 , Ayodhia Pitaloka Pasaribu 11 , Syahril Pasaribu 11 , Cholrawee Promnarate 8 , Awab Ghulam Rahim 16 , Pasathron Sirithiranont 1 , Hiwot Solomon 17 , Herawati Sudoyo 18 , Inge Sutanto 19 , Ngo Viet Thanh 6 , Nguyen Thi Tuyet-Trinh 20 , Naomi Waithira 1 , Adugna Woyessa 4 , Fazal Yamin Yamin 21 , Arjen Dondorp 1 , Julie A Simpson 22 , J Kevin Baird 23 , Nicholas J White 3 , Nicholas P Day 3 , Ric N Price 24
Affiliation  

BACKGROUND Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria. METHODS We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683). FINDINGS Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (-0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group). INTERPRETATION In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria. FUNDING UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).

中文翻译:

用于根治间日疟原虫疟疾的短期伯氨喹:一项多中心、随机、安慰剂对照的非劣效性试验。

背景 伯氨喹是唯一广泛使用的预防间日疟原虫疟疾复发的药物,但对标准 14 天方案的依从性很差。我们的目的是评估短期疗程(7 天)伯氨喹根治间日疟疾的疗效。方法 我们在八家医疗诊所(阿富汗、埃塞俄比亚、印度尼西亚和越南各两家)进行了随机、双盲、安慰剂对照、非劣效性试验。纳入了具有正常葡萄糖-6-磷酸脱氢酶 (G6PD) 且表现为无并发症的间日疟疾的患者(年龄≥6 个月)。患者接受标准血液杀裂虫治疗,并随机分配 (2:2:1) 接受 7 天受监督的伯氨喹(每天 1·0 mg/kg)、14 天受监督的伯氨喹(每天 0·5 mg/kg) , 或安慰剂。主要终点是在意向治疗人群中评估的 12 个月随访期间有症状的间日疟原虫寄生虫血症的发生率。与 14 天方案相比,每人年 0·07 次复发的边际被用于确定 7 天方案的非劣效性。该试验已在 ClinicalTrials.gov (NCT01814683) 上注册。2014 年 7 月 20 日至 2017 年 11 月 25 日期间,共有 2336 名患者入组。在 7 天伯氨喹组的 935 名患者中,有症状的复发性间日疟疾的发病率为每人每年 0·18(95% CI 0·15 至 0·21)次,0·16(0·13 至 0) ·18) 对于 14 天伯氨喹组的 937 名患者,差异为 0·02(-0·02 至 0·05,p=0·3405)。安慰剂组 464 名患者的复发率为每人年 0·96(95% CI 0·83 至 1·08)次。7 天组 935 名患者中有 9 名 (1·0%) 报告了在开始治疗后 42 天内可能与药物相关的严重不良事件,14 天组 937 名患者中有 1 名 (0·1%) 发生,无控制臂中的 464 个。严重不良事件中有四项是显着溶血(7 天组中有 3 项,14 天组中有 1 项)。解释 在 G6PD 正常的患者中,7 天伯氨喹的耐受性良好且不劣于 14 天伯氨喹。短期疗程可能会提高依从性,从而提高伯氨喹根治间日疟疾的有效性。通过联合全球健康试验计划 (MR/K007424/1) 和 Bill &
更新日期:2019-09-13
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