Evaluation of 4 Artemisinin-based Combinations for Treating Uncomplicated Malaria in African Children
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 4,112
- 试验地点
- 8
- 主要终点
- PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.
研究概览
简要总结
The main objective is to compare the safety and efficacy of 4 artemisinin-based combinations (ACT) [amodiaquine-artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and chlorproguanil/dapsone plus artesunate] for single and repeat treatments of uncomplicated malaria in children. Safety will be determined by registering adverse events and grading, laboratory, and vital signs evaluations. Their incidence will be compared between the different study arms.
TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities. The leading EC approved the amendment on 2nd June 2008.
TO BE NOTED: since the batches of the study drug DHAPQ expire at the end of October 2008, and because of the unavailability of a new batch of DHAPQ from the manufacturer, the recruitment in the DHAPQ arm had to be discontinued on 30th October 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.
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
- •Males and Females aged between 6 months and 59 months inclusive. In the sites where CDA is tested all recruited children will be aged between 12 months and 59 months inclusive (this arm was discontinued on 17th February 2008). This criterion applies only for the recruitment in the first follow up. For the second follow up, children having been included in the first follow up are eligible, regardless of their age.
- •Body weight of 5 Kg and above.
- •Microscopically confirmed, monoinfection of Plasmodium falciparum (parasitaemia ≥ 2,000/μL to 200,000/μL).
- •Fever (axillary temperature at ≥ 37.5°C) or history of fever in the previous 24 hours.
- •Haemoglobin value ≥ 7.0 g/dl;
- •Signed (or thumb-printed whenever parents/guardians are illiterate) informed consent by the parents or guardians. Note the informed consent will be asked only at recruitment and will cover the whole period of the study, including second active follow up and passive case detection.
- •Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the trial.
排除标准
- •Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
- •Known hypersensitivity to the study drugs.
- •Severe malaria.
- •Danger signs: not able to drink or breast-feed, vomiting (> twice in 24hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand.
- •Presence of intercurrent illness or any condition (cardiac, renal, hepatic diseases) which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency.
- •Severe malnutrition (defined as weight for height <70% of the median NCHS/WHO reference).
- •Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carinii pneumonia in children born to HIV+ women.
研究组 & 干预措施
3
AL
干预措施: artemether-lumefantrine (AL) (Drug)
1
AS-AQ
干预措施: amodiaquine-artesunate (ASAQ) (Drug)
2
DHAPQ
TO BE NOTED: since the batches of the study drug DHAPQ expire at the end of October 2008, and because of the unavailability of a new batch of DHAPQ from the manufacturer, the recruitment in the DHAPQ arm had to be discontinued on 30th October 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.
干预措施: dihydroartemisinin-piperaquine (DHAPQ) (Drug)
4
Lapdap + AS
TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.The leading EC approval was obtained on 2nd June 2008.
干预措施: Lapdap (Chlorproguanil-Dapsone) + artesunate (AS) (Drug)
结局指标
主要结局
PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.
时间窗: Day 28
PCR adjusted treatment failure up to day 28 (TF28A): all early failures before day 14 plus the recurrent parasitaemias detected at day 14 or later and classified by genotyping as recrudescence.
时间窗: Day 28
次要结局
- PCR unadjusted treatment failure up to day 63 (TF63U): TF28U plus all cases of recurrent parasitaemia (symptomatic or asymptomatic) detected between day 29 and day 63 by passive follow up, regardless of genotyping(Day 63)
- PCR adjusted treatment failure for the whole period of passive surveillance (TFAPS): TF28A plus all episodes of recurrent parasitaemia identified as recrudescence by genotyping.(Day 28)
- Clinical malaria after first active follow-up;(28 Days)
- TF second clinical episode (D28 and D63);(63 days)
- Hb changes day 3, 7, 14 and 28 (first and second follow up);(28 days)
- Changes in the frequency of mutations in the dihydrofolate reductase (DHFR) gene at day 0 first follow-up and day re-appearance of parasitaemia (for patients treated with CDA - NOTE that CDA arm was discontinued on 17.02.2008).
- Fever clearance time.
- Asexual parasite clearance time.
- Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment (for both active follow-ups);(28 days)
- Clinical malaria after second active follow-up;(Up to seven months)
- Safety profiles including significant changes in relevant laboratory values.(Up to seven months)