Efficacy and Safety of Artesunate-amodiaquine and Artemether-lumefantrine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Democratic Republic of the Congo: a Randomized Controlled Trial (TES2022)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,260
- 试验地点
- 7
- 主要终点
- PCR adjusted efficacy
研究概览
简要总结
Malaria remains a public health concern, despite efforts that are invested in the disease control. The Democratic Republic of the Congo (DRC) is one of the most affected countries in Sub Saharan Africa. Artemisinin-based combination treatments (ACTs) are recommended for the treatment of uncomplicated malaria. However, reported cases of mutations that confer to Plasmodium falciparum resistance to artemisinin (the main component of ACTs) constitute a threat to malaria control, particularly in Sub Saharan Africa. Therefore, the recommendation of the World Health Organization to conduct regularly test efficacy studies in endemic countries is paramount.
The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®) and artemether-lumefantrine (Coartem Dispersible®) at day 28 for the treatment of uncomplicated Plasmodium falciparum malaria in eight surveillance sites around DRC.
详细描述
This is a phase IV, randomized, open label, 2-arm trial. It will be performed in eight malaria sentinel sites around DRC. Children aged 6 to 59 months with confirmed Plasmodium falciparum uncomplicated malaria will be enrolled after informed consent granted by a parent or guardian. They will be randomized to receive either artesunate-amodiaquine or artemether lumefrantrine during 3 days (directly observed treatment) and then followed up until day 28. At each visit, clinical examination (including collection of safety data) will be done and malaria testing as well. Dried blood spots will also be prepared whenever microscopy is performed, in order to assess resistance markers and perform the genotyping of the parasite for PCR-adjusted efficacy. Hemoglobin level will be measured on the recruitment day and then every two weeks until day 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •children aged 6 to 59 months
- •monoinfection with Plasmodium falciparum with asexual parasite count of 2,000 to 200,000/µL
- •axillary temperature ≥ 37.5 °C
- •ability to swallow oral medication
- •ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule;
- •informed consent from a parent or a guardian
- •living within the study catchment area
- •absence of severe manutrition
- •absence of infectious diseases that can be responsible of fever
- •absence of allergy to the study drugs
排除标准
- •presence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO;
- •body weight < 5kg
- •hemoglobin level < 5g/ dL or hematocrit < 15%
- •presence of severe malnutrition
- •presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
- •regular medication, which may interfere with antimalarial pharmacokinetics;
- •malaria treatment within 2 days prior to recruitment
- •history of hypersensitivity reactions or contraindications to any of the medicines being tested or used as alternative treatment;
- •body weight below 5 kg
研究组 & 干预措施
Artesunate-amodiaquine
tablets of ASAQ Winthrop®
干预措施: Artesunate-amodiaquine (Drug)
Artemether-lumefantrine
tablets of Coartem Dispersible®
干预措施: Artemether-lumefantrine (Drug)
结局指标
主要结局
PCR adjusted efficacy
时间窗: day 28
Absence of fever and negative blood smear during the follow-up until day 28 or new infection occurred during the follow-up.
次要结局
- Prevalence of HRP2 deletion(Baseline)
- Quantification of Lumefantrine(day 7)
- Proportion of adverse events and serious adverse events(day 28)
- Prevalence of resistance markers at baseline(Baseline)
研究者
Prof. Gauthier Mesia Kahunu
Professor
Ministry of Public Health, Democratic Republic of the Congo