Evaluation of the Efficacy and Safety of Primaquine for Clearance of Gametocytes in Uncomplicated Falciparum Malaria in Uganda
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 468
- 试验地点
- 1
- 主要终点
- Mean number of days to gametocyte clearance (gametocyte clearance time, GCT)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of lower doses of primaquine compared to the dose recommended by the WHO for reducing P. falciparum gametocytes in the infected human host to prevent transmission of falciparum malaria to the anopheles mosquito vector.
详细描述
A single dose of 0.75mg/kg primaquine base is recommended by the WHO to block transmission of falciparum malaria from infected humans to mosquitoes by clearing gametocytes. However, the optimal dose for safety and efficacy has not been evaluated. Dose-finding data is important because primaquine has a dose-dependent risk of causing haemolysis (destruction of blood cells) in pre-disposed individuals, such as those with G6PD deficiency. G6PD deficiency is most prevalent in malaria-endemic areas. Therefore, it is essential that data on primaquine's safety is available in such areas.
The investigators hypothesise that lower doses of primaquine have a lower risk of adverse effects compared to the WHO-recommended dose, but retain the transmission-blocking efficacy.
The investigators propose to test this hypothesis in a four-arm clinical trial with a non-inferiority design to evaluate the efficacy and a superiority design to evaluate the safety of the WHO dose (0.75mg/kg) and lower doses of primaquine for clearance of P. falciparum gametocytes in children in Uganda. The study will include a pharmacokinetic analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >/= 1 year and </= 10 years
- •Weight over 10kg
- •Fever >38 degrees C (tympanic) or history of fever in the last 24 hours
- •P. falciparum parasitaemia <500 000/µl
- •Normal G6PD enzyme function
排除标准
- •Enrolled in another study
- •Evidence of severe illness/ danger signs
- •Known allergy to study medications
- •Haemoglobin < 8g/dL)
- •Started menstruation
- •Pregnancy or breastfeeding
- •Primaquine taken within the last 4 weeks
- •Blood transfusion within the last 90 days
- •Non-falciparum malaria co-infection
研究组 & 干预措施
Placebo
Non-active drug
干预措施: Primaquine (Drug)
Low dose primaquine (PQ1)
Lowest experimental dose of primaquine base: 0.1mg/kg
干预措施: Primaquine (Drug)
Intermediate dose primaquine (PQ2)
Intermediate experimental dose of primaquine base: 0.4mg/kg
干预措施: Primaquine (Drug)
Reference dose primaquine (PQ-R)
WHO-recommended dose of primaquine base: 0.75mg/kg
干预措施: Primaquine (Drug)
结局指标
主要结局
Mean number of days to gametocyte clearance (gametocyte clearance time, GCT)
时间窗: 14 days
Mean number of days per treatment arm for gametocytes to become undetectable using sub-microscopic molecular testing methods (real-time nucleic acid sequence-based amplification, QT-NASBA)and interpolated from measured data points.
Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up
时间窗: 28 days
Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up
次要结局
- Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up(14 days)
- Requirement for blood transfusion(28 days)
- Follow-up day of Hb nadir(28 days)
- Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug(28 days)
- Incidence of gastrointestinal symptoms after taking study drug(6 days)