Efficacy of Amodiaquine-Artesunate and Artemether-Lumefantrine for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Pweto, Democratic Republic of Congo, 2008
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Epicentre
- 入组人数
- 301
- 试验地点
- 1
- 主要终点
- PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population
研究概览
简要总结
In the Democratic Republic of Congo (DRC), malaria is an important cause of morbidity and mortality. It is estimated that malaria is responsible for 30% of admissions to hospital averaged throughout the country and for 25-30% mortality in children under five.
In 2005, DRC adopted artesunate and amodiaquine (ASAQ) as first-line anti-malarial treatment. As WHO recommended that the efficacy of antimalarial drugs was monitored regularly to avoid an upsurge of mortality and morbidity due to continued use of ineffective drugs, a randomized, non-inferiority open-label trial was conducted in Katanga, in order to compare the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine (AL),
Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolledand randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed.
Between April 2008 and March 2009, 301 childrenwere included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131) in the ASAQ group and 15.2% (19/125) in the AL group). After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8) in the ASAQ group and 99.1% (95%CI, 94.9-99.9) in the AL group (difference -0.7%, one sided 95%CI -3.1). Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated.
Both ASAQ and AL are highly effective and currently adequate as the first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces.
详细描述
Study design and site An open randomized study was conducted to test the hypothesis that the risk of recurrent parasitaemia after 42 days is not inferior in the group receiving artesunate and amodiaquine (ASAQ) regimen compared to the group receiving artemether-lumefantrine (AL) regimen.
The patients were recruited from the outpatient department of the general reference hospital of Pweto, health district of Pweto, province of Katanga, Democratic Republic of Congo (DRC), between April 2008 and March 2009.
Procedures Children aged between six and 59 months and with a body weight ≥ 5kg were eligible for enrolment if they had P. falciparum infections (density threshold at inclusion between 2,000 and 200,000/µl), fever or history of fever in the previous 24 hours, no signs of severe malaria, no reported hypersensitivities of the studied drugs, and no serious concomitant febrile illness.
The children included were randomized in one of the two treatment arms, in a 1:1 ratio without any stratification. The randomization list was generated by a computer in blocks of six. Treatment allocations were kept in sealed and numbered opaque envelopes. Participants were enrolled in the same order in which they were diagnosed.
ASAQ (ASAQ Winthrop®, Sanofi-Aventis) was administered once daily for three days, as follows: one tablet of artesunate 25mg/amodiaquine 67.5 mg for children between 5 to 8.9 kg, artesunate 50mg/amodiaquine 135 mg for children between 9 to 17.9 kg. One tablet of artemether 20 mg/lumefantrine 120 mg; (Coartem® Novartis Pharma, Basel, Switzerland) was administered twice daily for three days to children with a body weight of 5 to 14.9 kg and two tablets were administered twice daily for three days to children with a body weight of 15 to 24.9 kg. All doses of drugs were administered under direct observation for the three days. Full doses of drugs were re-administered if a patient vomited within 30 min after receipt. Patients who vomited more than twice were excluded from the study.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Artesunate and Amodiaquine (ASAQ)
children receiving fixed-dose combination of artesunate and amodiaquine
干预措施: ASAQ Winthrop® Sanofi Aventis (Drug)
Arthemeter and Lumefantrine (AL)
children receiving fixed-dose combination of arthemeter and lumefantrine
干预措施: Coartem®, Novartis (Drug)
结局指标
主要结局
PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population
时间窗: 42 days
Outcomes were classified according to 2009 WHO guidelines as adequate clinical and parasitological response, early treatment failure, late clinical failure, late parasitological failure or follow-up interrupted. The per protocol population comprised only the patients who were followed throughout the protocol, defined follow-up period and in whom a clear treatment outcome can be determined. The risk of failure for each treatment group was calculated as the proportion of patients classified as failure divided by the number of patients in the evaluable population.
次要结局
- PCR-unadjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined in the per-protocol population(42 days)
- PCR-unadjusted clinical and parasitological cure rate up to day 28 of the follow-up period determined in the per protocol population(28 days)
- PCR-adjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined by a survival analysis(42 days)
- PCR-unadjusted clinical and parasitological cure rate up to day 42 of the follow-up period determined by a survival analysis(42 days)
- PCR-adjusted clinical and parasitological cure rate up to day 28 of the follow-up period determined in the per protocol population(28 days)