Confirmation of Artemisinin Tolerance in Malaria Parasites Trial in Kilifi
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 175
- 试验地点
- 3
- 主要终点
- The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate
研究概览
简要总结
The purpose of this study is to determine whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs.
详细描述
Artemisinin-based combination therapies (ACT) are the treatment of choice for episodes of uncomplicated P. falciparum malaria in all endemic countries. Rapid clearance of pathogenic blood stage malaria parasites by artemisinins is associated with swift recovery from mild malaria and reduced mortality from severe forms of the disease. In Kenya, and most malaria endemic sub-saharan Africa, artemether-lumefantrine has been introduced as first-line treatment in the public health care sector in 2006. Alarmingly, despite the short time since the introduction of ACTs artemisinin-resistant P. falciparum malaria has already emerged in South-East Asia, an area that has historically been the cradle of global spreads of drug-resistant malaria parasites.
In a previous study in Kilifi we have observed a significant drop in early response rates to treatment with two ACTs from 2005 to 2008. Conventional markers of potential changes in anti-parasitic host immunity, drug exposure, or baseline parasite biomass could not account for the observed time-dependent change in response rates.
This protocol aims to establish with reasonable confidence whether P. falciparum infections in Kilifi District have developed tolerance to the artemisinin class of drugs. We propose to study treatment response rates to an established 7-day regimen of artesunate alone in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 10 years, at the KEMRI study site in Pingilikani, Kilifi District, Kenya. The study will also assess (i) pharmacokinetic parameters of artesunate; (ii) ex vivo and in vitro chemosensitivity of parasite isolates to DHA; (iii) genetic determinants of altered in vivo and in vitro responses to DHA; and (iv) ex vivo expression profiles in normally vs. slowly responding P. falciparum infections before and during treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •aged between 6 months to 10 years, inclusive
- •mono-infection with P. falciparum detected by microscopy;
- •parasitaemia of 10,000-300,000/µl asexual forms;
- •presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h;
- •ability to swallow oral medication;
- •ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
- •informed consent from a parent or 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 severe acute malnutrition defined as weight for height <70% of the median NCHS/WHO (Appendix 2);
- •presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
- •regular medication, which may interfere with antimalarial pharmacokinetics or pharmacodynamic assessments (e.g., antibiotics with known antimalarial activity); and
- •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
Artesunate
Confirmation of artemisinin tolerance
干预措施: Artesunate (Drug)
结局指标
主要结局
The primary endpoint of this study will be the re-infection-adjusted day 28 failure rate
时间窗: Day 0-28
Cure is defined as clearance of asexual P. falciparum parasitemia until day 7 and no recrudescence of asexual P. falciparum parasitemia until day 28. Re-infections are defined by genetic fingerprinting methods as newly emerging parasite clones during follow-up.
次要结局
- The proportion of patients with positive malaria smears(24hr, 48hr, 72hr)
- The percentage reduction of parasitaemia from baseline(24hr, 48hr, 72hr)
- The mean time to parasite clearance(Up to day 7)
- The mean time to fever clearance(Up to day 7)
- To estimate the rates for late clinical and parasitological failure rates(Days 28 and 42)