The Tolerability and Safety of Low Dose Primaquine for Transmission Blocking in Symptomatic Falciparum Infected Cambodians
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 109
- 试验地点
- 1
- 主要终点
- Haemoglobin concentration
研究概览
简要总结
In Cambodia, falciparum is becoming more difficult to treat because drugs are becoming less effective. The investigators can help to try to prevent the spread of this resistant malaria by adding a drug that will make it more difficult for the mosquito to drink up the malaria in people's blood. If the mosquito cannot drink up the malaria, then the malaria cannot develop in the mosquito so it will not be able to inject malaria back into people when it bites. The drug the investigators will use is called primaquine.
Primaquine commonly causes the red cells in the blood to break apart if they are weak. Red cells need enzymes to work properly and weak red cells have low amounts of an enzyme called glucose 6 phosphate dehydrogenase (G6PD). The investigators want to know if treating malaria with primaquine will be safe for the red cells. To do this study, the investigators need to know if a subject has low G6PD or not.
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
- None
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 1 year
- •Presentation with a confirmed fever (≥ 38⁰C axilla or ≥ 37.5⁰C aural) or history of fever in previous 48 hours +/- other clinical features of uncomplicated malaria
- •Plasmodium falciparum monoinfection ≥ 1 asexual form / 500 white blood cells
- •Informed consent (written/verbal) provided by patient or relative/legal guardian
- •Signed Assent form for children aged 12 to < 18 years
排除标准
- •Clinical signs of severe malaria or danger signs
- •Pregnant or breast feeding
- •Unable or unwilling to take a pregnancy test (for women of child-bearing age)
- •Women intending to become pregnant in the next 3 months
- •Allergic to primaquine or DHA PP
- •Patients taking drugs known to cause acute intravascular haemolytic anaemia (AIHA) in G6PD deficiency e.g. dapsone, nalidixic acid
- •Patients on treatment for a significant illness e.g. HIV, tuberculosis (TB) treatment, steroids
- •On drugs that could interfere with anti-malarial pharmacokinetics like antiretrovirals, cimetidine, ketoconazole, antiepileptic drugs, rifampicin
研究组 & 干预措施
DHA PP plus primaquine, G6PD deficiency
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children <18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.
干预措施: Dihydroartemisinin piperaquine (DHA PP) (Drug)
DHA PP plus primaquine, G6PD deficiency
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children <18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.
干预措施: Primaquine (Drug)
DHA PP plus primaquine, G6PD normal
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children <18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.
干预措施: Dihydroartemisinin piperaquine (DHA PP) (Drug)
DHA PP plus primaquine, G6PD normal
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
Target dose of 0.25mg/kg primaquine given orally with first dose only of DHA PP, dosing by weight for children <18 years and standard 15mg primaquine dose for all adults ≥18 years. Small children (<25kg) will receive a primaquine suspension, adults receive 7.5mg or 15mg primaquine tablets.
干预措施: Primaquine (Drug)
DHA PP alone, G6PD deficiency
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
干预措施: Dihydroartemisinin piperaquine (DHA PP) (Drug)
DHA PP alone, G6PD normal
Standard Dihydroartemisinin piperaquine (DHA PP) dosing according to national guidelines, oral administration of one dose per day for three consecutive days. Target dosing is 2-4 mg/kg for DHA and 20 mg/kg for PP. Children (<30kg) will receive tablets of 20mg DHA and 160mg PP, while adults will receive tablets of 40mg DHA and 320mg PP.
干预措施: Dihydroartemisinin piperaquine (DHA PP) (Drug)
结局指标
主要结局
Haemoglobin concentration
时间窗: Day 7
Compare haemoglobin concentrations in g/dL between the G6PD deficient arm given DHA PP plus primaquine, and the G6PD normal arm receiving the same regimen
次要结局
- Proportion patients with ≥25% change in haemoglobin as a marker of intravascular haemolysis(Change from Day 0 to Day 7)
- Plasma haemoglobin concentration as a marker of intravascular haemolysis(Day 7)
- Urine colour change as a marker of intravascular haemolysis(Change from Day 0 to Day 7)
- Fractional change in haemoglobin as a marker of intravascular haemolysis(Change from Day 0 to Day 7)
- Primaquine volume of distribution(Day 0-7)
- Clearance rate of piperaquine(Day 0-28)
- Piperaquine volume of distribution(Day 0-28)
- Peak plasma concentration (Cmax) of piperaquine(Day 0-28)
- Determine G6PD enzyme activity(Day 0)
- Assess usefulness of field adapted WHO haemoglobin colour card vs. Hemocue(Day 0)
- Assess usefulness of rapid test for G6PDd in predicting acute intravascular haemolysis(Day 0)
- Clearance rate of primaquine(Day 0-7)
- Half life of primaquine(Day 0-7)
- Half life of piperaquine(Day 0-28)
- Area under the plasma concentration versus time curve - piperaquine(Day 0-28)
- Peak plasma concentration (Cmax) of primaquine(Day 0-7)
- Time to primquine peak plasma concentration (Tmax)(Day 0-7)
- Time to piperaquine peak plasma concentration (Tmax)(Day 0-28)
- Area under the plasma concentration versus time curve - primaquine(Day 0-7)