Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 2,100
- 试验地点
- 7
- 主要终点
- The primary endpoint will be the PCR-corrected and parasitological response (PCR corrected ACPR) at days 28 and 42. Change in this outcome measure will be assessed.
研究概览
简要总结
Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria. The Ministry of Health, Division of Malaria Control (DOMC) rolled out the use of artemether-lumefantrine as the first line treatment for uncomplicated malaria in 2006.The development of the ACTs and its derivatives are the most rapidly acting of all the current antimalarial drugs and recognition of their potential role as a component of combination therapy have led to several large trials aimed at assessing different combinations of existing drugs, and to the specific development of new combination drugs.
This proposal aims to (1) evaluate the efficacy of artemisinin-based anti-malaria combination drugs in different sites across Kenya (2) elucidate the markers of resistance to ACTs through molecular genetics and in this process further strengthen capacity in the proposed study sites as well as improve links between research and control ultimately to influence malaria treatment policy and practice.
Five groups in East Africa will conduct a multi-centre, randomised, two arm trial to assess the efficacy of dihydroartemisin-piperaquine with artemether-lumefantrine as the comparative drug. The network will determine antimalarial drug efficacy using standardised protocols and collate clinical responses and adverse events. Molecular markers to artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles in drug failure cases. Recrudescence or re-infections will be differentiated by analysis of the MSP1, MSP2 and GLURP genes and assess transmission dynamics post treatment. Data from these studies will be captured into a database developed by the network. The latter offers several advantages including
- Working towards the standardization of methodologies and common protocols as a way of comparing data across sites
- Pulling together datasets and conduct a multi-centre analysis
- Sharing and coordinating quality assurance mechanisms
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
- Single (Care Provider)
入排标准
- 年龄范围
- 6 Months 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 6 months - 5 years (in high endemic areas); 6 months to 10 years (in low endemic areas) inclusive.
- •Presence of axillary temperature > 37.5oC or rectal / tympanic temp > 38.0oC, or history of fever in the last 24 hours.
- •Monoinfection with Plasmodium falciparum with parasitaemia, asexual parasitemia between 2,000 - 200,000 p/µl (in areas of high transmission); 1,000-100,000p/ µl (in areas of low to moderate malaria transmission)
- •Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
- •Signed informed consent form by the parents or legal guardian.
排除标准
- •Presence of clinical danger signs: not able to drink or breast-feed, vomiting (>twice in 24 hours), recent history of convulsions (>1 in 24h), unconscious state, unable to sit or stand;
- •Mixed or mono-infection with another Plasmodium species detected by microscopy;
- •Presence of co-morbid infection (e.g. acute lower respiratory tract infection, severe diarrhoea with dehydration, Severe Anaemia) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases,Epilepsy, HIV/AIDS);
- •History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).
研究组 & 干预措施
Artemether lumefantrine
Tablets, 1-4 tablets (weight calculated dose), BD, at hr 0, 8, 24, 36, 48 and 60.
干预措施: Artemether lumefantrine (Drug)
Dihydroartemisinin piperaquine
Tablets, 2 paediatric tablets/1 adult tablet, OD, every 24 hours for 48 hours
干预措施: Dihydroartemisinin piperaquine (Drug)
结局指标
主要结局
The primary endpoint will be the PCR-corrected and parasitological response (PCR corrected ACPR) at days 28 and 42. Change in this outcome measure will be assessed.
时间窗: Day 28 and day 42
ACPR is defined as the absence of parasitaemia on day 42 irrespective of the temperature without previously meeting any of the criteria of early treatment failure or late clinical or parasitological failure. Patients with late asexual parasite reappearance will be considered ACPR if the CR analyses shows a new infection rather than a recrudescence (through PCR genotyping). The total treatment failure is defined according to the WHO criteria as the sum of early and late treatment failures.
次要结局
- Heart rate(Up to day 42)
- Respiratory rate(Up to day 42)
- Crude (PCR uncorrected) ACPR ratio at day 28 (PCR uncorrected ACPR)(Day 28)
- Fever Clearance Time (FCT)(0 to 48 hours)
- Comparison between adverse events related to artemether lumefantrine and dihydroartemisinin piperaquine(Up to day 42)
- Temperature(Up to day 42)
- Oxygen saturation(Up to day 42)
- Cure ratios at day 28, 42, (PCR corrected and PCR uncorrected). Change in this outcome measure will be assessed.(Day 28 and day 42)
- Changes of haemoglobin (Hb) concentration from day 0 to days 28, and 42(Day 0, day 28 and day 42)
- Number of participants with adverse events(Up to day 42)
- Asexual parasite clearance time (PCT)(Day 0 to day 28, upto day 42)
- Gametocyte carrier rates and geometric mean densities (excluding negatives) will be compared on days 7, 14, 28 and 42. Change in this outcome measure will be assessed.(Day 7, 14, 28 and 42)
研究者
Sabah Ahmed Omar
Centre Director of KEMRI CGMR-C and Study Principal Investigator
KEMRI-Wellcome Trust Collaborative Research Program