Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women With Malaria
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3,428
- 试验地点
- 6
- 主要终点
- Treatment Failure (PCR adjusted)
研究概览
简要总结
Malaria is the most important human parasitic disease and is responsible of high morbidity and mortality in resource-poor countries. Pregnant women, who are a high-risk group, are almost always excluded from clinical trials; thus, the investigators lack sufficient information on the safety and efficacy of most antimalarials in pregnancy. The recommendation of the World Health Organization to use artemisinin combination therapy (ACT) in the 2nd and 3rd trimester is already implemented in several African countries, however documentation of their efficacy and safety in pregnancy is still limited. Thus, the investigators propose to evaluate the efficacy and safety of 4 ACT(artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate and dihydroartemisinin-piperaquine), when used to treat pregnant women with P. falciparum malaria; the results will help to recommend the optimal therapy for this high-risk group in Africa.
详细描述
Malaria is the most important human parasitic disease. Although pregnant women are a high-risk group, they are almost systematically excluded from clinical trials, for fear of teratogenicity and embryotoxicity; thus, we generally lack sufficient information on the safety and efficacy of most antimalarials in pregnancy, as well as evidence-based recommendations for the prevention and treatment of malaria during pregnancy.
The WHO recommendation to use artemisinin combination therapy (ACT) in the 2nd and 3rd trimester is already implemented in several African countries. However, the documentation of their efficacy and safety in pregnancy is still limited, especially concerning the African contexts.
Therefore, we propose to test 4 fixed-dose combinations (artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate and dihydroartemisinin-piperaquine), to evaluate their efficacy and safety when administered to pregnant women (2nd and 3rd trimester) infected with P. falciparum. Explanatory variables will be collected for treatment failure (PCR-corrected) and for recurrent parasitaemia. The primary hypothesis tested will be the clinical equivalence (pair-wise non-inferiority) of the 4 treatment regimens with clinical equivalence defined as difference in treatment failure rates (PCR corrected) of 5% or less.
In addition, an attempt will be done to carry out in vitro testing at the time of recurrent infection. However, the success of the test will depend on the parasite density. In addition, blood samples collected on filter paper at day 0 and at day of recurrent parasitaemia will be genotyped for the search of known molecular markers related to drug resistance. Not all samples will be analyzed; rather these will be selected according to the therapeutic response so that the prevalence of molecular markers will be compared between treatment successes, true treatment failures and new infections.
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Gestation of at least 16 weeks and <37 weeks;
- •P. falciparum monoinfection of any density, with or without symptoms
- •Hb equal or higher than 7 g/dL;
- •At least 15 years old;
- •Residence within the health facility catchment's area;
- •Willing to deliver at the health facility;
- •Willing to adhere to study requirements (including in Zambia and Malawi, HIV VCT)
- •Ability to provide written informed consent; if the woman is minor of age/not emancipated, the consent must be given by a parent or legal guardian according to national law (however, in this case, the investigator is responsible to check that the woman herself is also freely willing to take part in the study, and the woman will be asked to sign for "assent").
排除标准
- •History of allergic reactions to the study drugs;
- •History of known pregnancy complications or bad obstetric history such as repeated stillbirths or eclampsia;
- •History or presence of major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis;
- •Current cotrimoxazole prophylaxis or ARV treatment;
- •Any significant illness at the time of screening that requires hospitalization, including severe malaria;
- •Intent to move out of the study catchment area before delivery or deliver at relative's home out of the catchment area.
- •Prior enrollment in the study or concurrent enrollment in another study.
- •Unable to take oral medication
- •Clear evidence of recent (1 week) treatment with antimalarials or antimicrobials with antimalarial activity (clindamycin; azythromycin; etc.)
研究组 & 干预措施
DHAPQ
Three-day treatment with dihydroartemisinin-piperaquine
干预措施: Dihydroartemisinin-piperaquine (Drug)
MQAS
Three-day treatment with mefloquine artesunate
干预措施: Artesunate-mefloquine (Drug)
AQAS
Three-day treatment with artesunate-amodiaquine
干预措施: Artesunate-amodiaquine (Drug)
AL
Three day treatment with artemether-lumefantrine (Coartem(R)
干预措施: Artemether-lumefantrine (Drug)
结局指标
主要结局
Treatment Failure (PCR adjusted)
时间窗: Day 63
Safety profiles including significant changes in relevant laboratory values
时间窗: Until delivery
次要结局
- Time to failure(Case by case)
- PCR unadjusted treatment failure(Day 63)
- Gametocyte carriage (gametocyte-weeks)(Case by case)
- Gametocytaemia (prevalence and density)(Day 7, 14, 21, 28 and 63 after treatment)
- Haemoglobin changes(Days 14, 28, 42 and 63)
- The presence of acute, chronic or past infection of the placenta (prevalence)(Delivery)
- Mean birth weight and prevalence of low birth weight newborns(Delivery)
- In vitro vitro and search of molecular markers related to drug resistance(At the time of recurrent infection)
- Determination of the PK profile of MQ, AQ and PQ (on 120 women/treatment)(Case by case)
- Asexual parasite clearance time(Days to 2 consecutive negative blood slides.)