Efficacy and Safety of Artesunate-amodiaquine, Artemether-lumefantrine and Dihydroartemisinine-piperaquine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Democratic Republic of Congo: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,615
- 试验地点
- 6
- 主要终点
- PCR-adjusted efficacy
研究概览
简要总结
The Democratic Republic of the Congo (DRC) is among the countries most affected by malaria in Sub-Saharan Africa. Condidering its size and the geographic position, the DRC is meant to play a major role in the malaria control in the region. The National Malaria Control program recommends artemisinin-based combination treatments (ACTs), in particular artesunate-amodiaquine or artemether-lumefrantrine for the treatment of uncomplicated malaria. Previous studies indicated that ACTs are still effective, with efficacy above the required threshold of 90%. It is required to assess regularly the efficacy of antimalarial drugs, in order to ascertain the relevance of treatment guidelines such that, in case of increasing failure rates, alternative options can be decided ontime.
The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®), artemether-lumefantrine (Coartem Dispersible®) and dihydro-artemisinin-piperaquine (Eurartesim®) at day 42 in the treatment of uncomplicated Plasmodium falciparum malaria in six surveillance sites around DRC.
详细描述
This is a phase 4, randomized, open labelled clinical trial, aiming to assess efficacy and safety of 3 ACTs in the treatment of uncomplicated malaria in the Democratic Republic of the Congo. Children diagnosed with uncomplicated Plasmodium falciparum uncomplicated malaria will be randomized and followed-up during 42 days.
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
- •axillary temperature ≥ 37.5 °C or history of fever during the 24 h before recruitment
- •monoinfection with Plasmodium falciparum with asexual parasite count of 2,000 to 200,000/µL
- •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/guardian
- •absence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO (2000)
- •absence of severe malnutrition according to WHO child growth standards
- •absence of febrile condition 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 or hepatic diseases, HIV/AIDS)
- •absence of regular medication, which might interfere with antimalarial pharmacokinetics
- •absence of history of hypersensitivity reactions or contraindication to any medicine being tested or used as alternative treatment
排除标准
- •presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to the definitions of WHO
- •body weight < 5kg
- •hemoglobin level < 5g/ dL
- •mixed or monoinfection with another Plasmodium species detected by microscopy
- •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;
- •history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)
研究组 & 干预措施
artesunate-amodiaquine
Tablets containing 25 mg of artesunate and 67.5 mg of amodiaquine: one tablet daily for three days children weighing 4.5 to 8 kg, and tablets containing 50 mg of artesunate and 135 mg of amodiaquine: one tablet daily for three days for children weighing 9 to 17 kg.
干预措施: artesunate-amodiaquine (Drug)
artemether-lumefantrine
Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine. Each dose to be taken with high-fat food or drinks (for example milk).
One tablet twice daily for children weighing 5 to <15 kg, two tablets twice daily for those weighing 15 to <25 kg and three tablets twice daily for those weighing 25 to < 35 kg, for three days.
干预措施: artemether-lumefantrine (Drug)
Dihydroartemisinine-piperaquine
Tablets containing 20 mg of dihydroartemisinine and 160 mg of piperaquine. Half a tablet once daily for children weighing 5 to <7 kg, one tablet once daily for those weighing 7 to <13 kg, and two tablets once daily for those weighing 13 to <24 kg, for three days.
干预措施: Dihydroartemisinine-piperaquine (Drug)
结局指标
主要结局
PCR-adjusted efficacy
时间窗: day 42
the proportion of children with PCR adequate clinical and parasitological response
次要结局
- PCR-unadjusted efficacy(day 42)
- K-13 propeller polymorphisms(day 42)
- incidence of adverse events(day 42)
研究者
Prof. Gauthier Mesia Kahunu
Professor
Ministry of Public Health, Democratic Republic of the Congo