Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens.
Improving the radical cure of vivax malaria (IMPROV): a study protocol for a multicentre randomised, placebo-controlled comparison of short and long course primaquine regimens.
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DOI：
10.1186/s12879-015-1276-2
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发表时间：
2015-12-07
影响因子：
3.7
通讯作者：
IMPROV Study Group
中科院分区：
文献类型：
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作者：
IMPROV Study Group
间日疟原虫疟疾是发病的一个主要原因，并被认为是一些流行地区死亡的一个重要因素。目前推荐的根治间日疟原虫的治疗方案包括杀线虫抗疟药（通常为氯喹）联合伯氨喹14天方案。长期的治疗过程经常导致依从性和有效性差。疗程较短，每日剂量较高的伯氨喹有可能提高依从性，从而提高疗效，而不会影响安全性。拟议的多中心随机临床试验旨在提供证据，在各种地方性设置的安全性和有效性的高剂量短期伯氨喹葡萄糖-6-磷酸脱氢酶（G6 PD）正常患者。本研究设计为安慰剂对照、双盲、随机试验，在四个国家进行：印度尼西亚、越南、阿富汗和埃塞俄比亚。将诊断为间日疟的G6 PD正常患者随机接受7天或14天高剂量伯氨喹或安慰剂。将G6 PD缺陷（G6 PDd）患者分配至每周伯氨喹剂量，持续8周。直接观察所有治疗，复发性发作采用与入组时分配的治疗相同的治疗。每天对患者进行随访直至治疗完成，每周随访直至治疗开始后8周，然后每月随访直至治疗开始后1年。主要终点是12个月随访期间所有个体症状性复发间日疟原虫寄生虫血症的发生率（每人年），控制部位，比较7天与14天伯氨喹治疗组。次要终点是其他疗效指标，如不同时间点的发生率风险。其他终点是溶血和严重不良事件的风险。本研究已获得英国和澳大利亚以及所有参与国家的相关机构伦理委员会的批准。将通过同行评审的出版物和学术报告传播结果，为间日疟治疗政策提供信息。研究结果将有助于更好地了解伯氨喹的风险和益处，这对于说服政策制定者和临床医生根治间日疟的重要性至关重要，有助于减少传播和减少寄生虫库。ClinicalTrials.gov标识符：NCT 01814683。2013年3月18日注册本文的在线版本（doi：10.1186/s12879-015-1276-2）包含补充材料，授权用户可以使用。
Plasmodium vivax malaria is a major cause of morbidity and recognised as an important contributor to mortality in some endemic areas. The current recommended treatment regimen for the radical cure of P. vivax includes a schizontocidal antimalarial, usually chloroquine, combined with a 14 day regimen of primaquine. The long treatment course frequently results in poor adherence and effectiveness. Shorter courses of higher daily doses of primaquine have the potential to improve adherence and thus effectiveness without compromising safety. The proposed multicentre randomised clinical trial aims to provide evidence across a variety of endemic settings on the safety and efficacy of high dose short course primaquine in glucose-6-phosphate-dehydrogenase (G6PD) normal patients. This study is designed as a placebo controlled, double blinded, randomized trial in four countries: Indonesia, Vietnam, Afghanistan and Ethiopia. G6PD normal patients diagnosed with vivax malaria are randomized to receive either 7 or 14 days high dose primaquine or placebo. G6PD deficient (G6PDd) patients are allocated to weekly primaquine doses for 8 weeks. All treatment is directly observed and recurrent episodes are treated with the same treatment than allocated at the enrolment episode. Patients are followed daily until completion of treatment, weekly until 8 weeks and then monthly until 1 year after initiation of the treatment. The primary endpoint is the incidence rate (per person year) of symptomatic recurrent P. vivax parasitaemia over 12 months of follow-up, for all individuals, controlling for site, comparing the 7 versus 14-day primaquine treatment arms. Secondary endpoints are other efficacy measures such as incidence risk at different time points. Further endpoints are risks of haemolysis and severe adverse events. This study has been approved by relevant institutional ethics committees in the UK and Australia, and all participating countries. Results will be disseminated to inform P. vivax malaria treatment policy through peer-reviewed publications and academic presentations. Findings will contribute to a better understanding of the risks and benefits of primaquine which is crucial in persuading policy makers as well as clinicians of the importance of radical cure of vivax malaria, contributing to decreased transmission and a reduce parasite reservoir. ClinicalTrials.gov Identifier: NCT01814683. Registered March 18, 2013 The online version of this article (doi:10.1186/s12879-015-1276-2) contains supplementary material, which is available to authorized users.