A Double Blind Randomized Controlled Trial of Dihydroartemisinin-piperaquine Alone and in Combination With Single Dose Primaquine to Reduce Post-treatment Malaria Transmission.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Gametocyte prevalence on day 7 after initiation of treatment
研究概览
简要总结
Primaquine (PQ) is currently the only available drug that can clear the mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. A major caveat to the use of primaquine in mass adminsitrations for the reduction of malaria transmission is that metabolism of the drug in individuals with glucose-6 phosphate dehydrogenase (G6PD) deficiency can lead to transient haemolysis. The haemolytic side effect of PQ is dose-related. Haemolysis is more commonly observed after prolonged PQ treatment but has also been observed in African populations following a single dose of PQ. This haemolysis was self-limiting, largely restricted to G6PD deficient individuals and did not lead to clinical symptoms. Nevertheless, any drug-induced haemolysis is reason for concern and the World Health Organization has therefore reduced the recommended dose of single low dose primaquine from 0.75mg/kg to 0.25mg/kg. This dosage is deemed safe without prior G6PD or Hb screening. However, there is limited direct evidence on the extent to which this dosage of PQ prevents malaria transmission to mosquitoes.
In the current study, the investigators will assess the efficacy of DP in combination with low-dose PQ to prevent onward malaria transmission. The investigators will perform the investigators study in individuals aged 5-15 years who are carry microscopically detectable densities of P. falciparum gametocytes. This age group is chosen because asexual parasite carriage and gametocyte carriage are common in this age group. All enrolled individuals will receive a full three-day course of DP, and will be randomized to receive a dose of primaquine or placebo with their third dose. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For all individuals, the effect of treatment on infectivity to mosquitoes will be assessed by membrane feeding assays at two time points.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Microscopically detectable P. falciparum gametocyte carriage
排除标准
- •Age < 5 years or > 15 years
- •Non-falciparum malaria co-infection
- •Malaria parasite density ≥ 200,000 parasites/µL
- •Clinical symptoms indicating severe malaria
- •Axillary temperature ≥ 39°C
- •Body Mass Index (BMI) below 16 or above 32 kg/m2
- •Haemoglobin concentration below 9.5 g/dL
- •Anti-malarials taken in last 2 days
- •For women: Pregnancy (assessed by clinical examination and urine pregnancy test) or lactation
- •Known hypersensitivity to DP or PQ
- •History and/or symptoms indicating chronic illness
- •Current use of tuberculosis or anti-retroviral medication
- •Unable to give written informed consent
- •Unwillingness to participate in two membrane feeding assays
- •Travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, - Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan
- •Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
- •Taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride
- •Known disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia
- •Taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine)
- •Blood transfusion within last 90 days
研究组 & 干预措施
Dihydroartemisínin-piperaquine (Artekin)
Dihydroartemisínin-piperaquine combination alone
干预措施: Dihydroartemisinin-piperaquine combination (Artekin) (Drug)
Dihydroartemisinin-piperaquine, Primaquine
Dihydroartemisinin-piperaquine with single-dose 0.25mg/kg Primaquine
干预措施: Dihydroartemisinin-piperaquine combination (Artekin) (Drug)
Dihydroartemisinin-piperaquine, Primaquine
Dihydroartemisinin-piperaquine with single-dose 0.25mg/kg Primaquine
干预措施: Primaquine (Drug)
结局指标
主要结局
Gametocyte prevalence on day 7 after initiation of treatment
时间窗: day 7 of follow-up
Gametocyte prevalence on day 7 after initiation of treatment is measured by molecular methods.
次要结局
- Haematological recovery(14 days during follow-up)
- Gametocyte carriage during follow-up(14 days during follow-up)
- Gametocyte sex-ratio(14 days of follow-up)
- Transmission to Anopheles gambiae mosquitoes(Day 3 and 7 during follow-up)