Phase III Study to Study the Clinical Response to ACT Fixed Dose Combination in 42 Days in Uncomplicated Malaria in Cameroon
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 720
- 试验地点
- 2
- 主要终点
- Clinical Efficacy
研究概览
简要总结
To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in 720 children with acute uncomplicated P. falciparum malaria, in two different endemic ecological areas - Savanna and equatorial forest regions of Cameroon.
We have set as specific objectives:
- To assess the efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 14 and 28 days follow up period in children with acute uncomplicated P. falciparum malaria in two different endemic areas.
- To evaluate the safety of artesunate-amodiaquine, dihydroartemisinin-piperaquine, in comparison with artemether-lumefantrine during 42 days follow up period in children with acute uncomplicated P. falciparum malaria.
- To determine parasite clearance time (PCT) and fever clearance time (FCT) following the administration of the three trial regimens.
- To investigate the treatment response based on WHO criteria (WHO, 2003) in patients in all groups after trial.
- To investigate the Single Nucleotide Polymorphisms (SNPs) and microsatellite markers of genes associated with drug resistance
详细描述
Methodology Children of either gender, between 6 months (> 5kg) and 10 years of age, with acute uncomplicated P. falciparum infection, who fulfil all of the inclusion and have none of exclusion criteria will be enrolled in the study. They will be randomised to receive the three trial arms, i.e, Study Arm-A: artesunate-amodiaquine, Study Arm-B: dihydroartemisinin-piperaquine and Study Arm-C: artemether-lumefantrine at the ratio of 2:2:1 and will be hospitalised over a 3-day period to facilitate the supervised administration of the study drugs and full clinical and laboratory assessment and observation of early adverse effects. On discharge, participants will be required to report to the study clinic on days 7, 14, 21,28, 35 and 42 or at any other time when clinical sign(s)/symptom(s) of malaria is suspected. The number of participants is about 720 children
Inclusion Criteria
- Children of either gender, aged between 6 months (> 5kg) and 10 years.
- Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000 parasites/μl.
- Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in the preceding 24 hours.
- Able to ingest tablets orally (either suspended in water or uncrushed with food).
- Willing to participate in the study with written assent from parent/guardian. Parental authorization will be obtained for children less than 8 years old and documented assent of parents/guardians for children 8-10 years.
- Willing and able to attend the clinic on stipulated regular follow-up visits.
Exclusion Criteria
• Any of the following "danger signs of severe malaria": Not able to drink or breast feed Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within previous 24 hours) Lethargic/unconscious
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 6 Months 至 120 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children of either gender, aged between 6 months (> 5kg) and 10 years.
- •Suffering from acute uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density of 1,000 to 100,000 parasites/μl.
- •Presenting with fever (axillary temperature ≥ 37.5oC) or having a history of fever in the preceding 24 hours.
- •Able to ingest tablets orally (either suspended in water or uncrushed with food).
- •Willing to participate in the study with written assent from parent/guardian. Parental authorization will be obtained for children less than 8 years old and documented assent of parents/guardians for children 8-10 years.
- •Willing and able to attend the clinic on stipulated regular follow-up visits.
排除标准
- •Any of the following "danger signs of severe malaria": Not able to drink or breast feed Persistent vomiting (>2 episodes within previous 24 hours) Convulsions (>1 episode within previous 24 hours) Lethargic/unconscious
- •Signs/symptoms indicating severe/complicated malaria according to WHO criteria (WHO definition).
- •Concomitant illnesses, underlying chronic hepatic or renal disease, abnormal cardiac rhythm, hypoglycaemia, jaundice, respiratory distress,
- •Serious gastrointestinal disease, severe malnutrition (W/H < 70%) or severe anaemia (haemoglobin < 5 g/dl).
- •Known hypersensitivity to the study drugs.
研究组 & 干预措施
Artesunate-Amodiaquine
As a fixed-dose combination of artesunate-amodiaquine developed by Sanofi-Aventis (France). It has the advantage of being a 3-day regimen usable by all age groups and potentially low cost. tablets are administered per every day at dose of 25mg/67.5mg for those between 4,5kg and 9kg for 48H
干预措施: Artesunate-Amodiaquine (Drug)
Dihydroartemisinine_Piperaquine
As a fixed-dose combination of dihydroartemisinin-piperaquine which is produced by Fouley (China). It is a potentially low cost 2-day regimen that has been used in children between 5-10kg as half a tablet of 40mg/320mg every day for 48H
干预措施: Dihydroartemisinine-Piperaquine (Drug)
Artemeter-Lumefantrine
This is the active comparator as a fixed-dose combination of artemether and lumefantrine which is produced by Novartis (Switzerland). The drug will be used as the comparator because it is the only fixed-dose combination with artemether currently available. Administered in children as tablets containing Artemether-Lumefantrine at (20mg/120mg) for body weights of 5-10kg every 12H within 48H.
干预措施: Artemether-lumefantrine combination (Drug)
结局指标
主要结局
Clinical Efficacy
时间窗: 42 days
Patient's trial outcome will be classified according to the WHO guidelines (WHO 2003) with application as follows: Early Treatment Failure (ETF); Late Clinical Failure (LCF); Late Parasitological Failure (LPF); Adequate Clinical and Parasitological Response (ACPR) - Absence of parasitaemia on day 42 irrespective of temperature without previously meeting any of the criteria of early treatment failure or late clinical failure or late parasitological failure
次要结局
- Safety by measure of changes in Physiologic, Blood, Liver and Kidney functions to define AE & SAEs(42 days)
研究者
Wilfred F. Mbacham, ScD
PI
University of Yaounde 1