Efficacy and Bio-availability of Artemether-Lumefantrine Fixed Combination in Severely Malnourished Children Compared to Non-severely Malnourished Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Epicentre
- 入组人数
- 399
- 试验地点
- 2
- 主要终点
- Proportion of adequate clinical and parasitological response after PCR correction
研究概览
简要总结
The general objective of the study is to answer to the question: "Is the current dose of AL less efficacious in the severely malnourished compared to the non-severely malnourished children, and is PK in cause?" We aim to assess whether the current treatment dose is adequate for children with severe acute malnutrition, and we hope results will guide further recommendations for malaria treatment in this specific population.
详细描述
Study hypothesis:
We hypothesize that AL efficacy might be impaired in severely malnourished children, due to impaired bio-availability of antimalarial drugs in this population.
Objectives:
The general objective of the study is to answer to the question: "Is the current dose of Artemether-Lumefantrine (AL) less efficacious in the severely malnourished compared to the non-severely malnourished children, because of impaired bio-availability?" We aim to assess whether the current treatment dose should be adjusted for this specific population.
The primary objective of the study is to compare the rates of treatment failure (after PCR correction) between severely malnourished and non-severely malnourished children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 6 and 59 months
- •Weight ≥ 5 kg
- •P. falciparum monoinfection confirmed on a thick blood film
- •Parasitic density between 1,000 and 200,000 asexual forms/µL of blood.
- •Measured axillary temperature ≥ 37.5 ° C or history of fever during the previous 24 hours
- •High probability of compliance with follow-up visits (no near-term travel plans)
- •Consent of a parent or guardian who is at least 18 years of age.
- •According to the group: in severely malnourished, weight-for-height z-score <-3 SD or MUAC <115 mm, and in non-severely malnourished, weight-for-height z-score ≥- 3 standard deviations (SD), and MUAC≥ 115 mm.
排除标准
- •General danger signs or signs of complicated malaria as defined by the WHO (Appendix 1)
- •Mixed or mono-infection with another Plasmodium species detected by microscopy
- •Severe anemia (hemoglobin <5 g / dL)
- •Known underlying chronic or severe disease (e.g. cardiac, renal or hepatic disease, tuberculosis, sickle cell)
- •Known HIV/AIDS infection
- •Known history of hypersensitivity or contra-indication to any of the study medications: artemether, lumefantrine (first-line medications), or artesunate, amodiaquine (rescue medications)
- •Presence of febrile conditions due to diseases other than malaria which could alter the outcome of the study
- •History of a full treatment course with AL in the past 14 days.
- •Height-for-age <-3 Z scores
- •Severe complications of malnutrition requiring hospitalization in intensive care or stabilization: Severe signs of kwashiorkor, Anorexia (failure to the appetite test), Hyperemesis, Severe acute infection, Hypothermia <35 ˚ C (axillary) or hypoglycemia, Diarrhea with dehydration, Lethargy, coma, Clinical signs of vitamin A deficiency (xerophthalmia)
研究组 & 干预措施
Artemether-Lumefantrine
All patients will receive Artemether-Lumefantrine and the endpoints will be compared between the two populations of severely malnourished and non-severely malnourished children
干预措施: Artemether-lumefantrine fixed combination (Drug)
结局指标
主要结局
Proportion of adequate clinical and parasitological response after PCR correction
时间窗: 28 days
Standard primary outcome as defined wy the WHO guidelines for assessing antimalarial efficacy
次要结局
- Bio-availability of lumefantrine(21 days)
- Type and frequency of adverse events(42 days)
- Percentage of adequate clinical and parasitological response corrected by PCR(42 days)
- Proportion of treatment failures by types (Early Treatment Failure, Late Clinical Failure, Late Parasitological Failure)(28 and 42 days)
- Proportion of reinfection and recrudescence(28 and 42 days)