Efficacy, Safety, and Pharmacokinetics of Sulphadoxine-pyrimethamine-amodiaquine (SP-AQ), SP-AQ Plus Primaquine, Dihydroartemisinin-piperaquine (DP), DP Plus Methylene Blue for Preventing Transmission of P. Falciparum Gametocytes in Mali
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Mosquito infectivity assessed through membrane feeding assays
研究概览
简要总结
The purpose of this study is to determine the most efficacious transmission blocking drug regimen for seasonal malaria chemoprophylaxis in Mali. The primary outcome measure will be the proportion of mosquitoes infected pre and post-treatment, assessed through membrane feeding and measured by oocyst prevalence in mosquitoes dissected on day 7 post feed. Primary endpoint will be a within group comparison between the mean of the pretreatment infectivity (Day 0) and infectivity at 7 days post first dose.
详细描述
Protocol will be shared on request.
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 (Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 50 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Glucose-6-phosphate dehydrogenase (G6PD) normal defined by CareStart™ G6PD rapid diagnostic test (RDT) or the OSMMR2000 G6PD semi-qualitative test
- •Absence of symptomatic falciparum malaria, defined by fever upon enrollment
- •Presence of P. falciparum gametocytes on thick blood film at a density >30 gametocytes/µL (i.e. ≥2 gametocytes recorded in the thick film against 500 white blood cells)
- •No allergies to study drugs
- •No self-reported use of antimalarial drugs over the past 7 days (as reported by the participant)
- •Hemoglobin ≥ 10 g/dL
- •Individuals weighing <80 kg
- •No evidence of severe or chronic disease
- •Written, informed consent
排除标准
- •Age < 5 years or > 50 years
- •Female gender
- •Blood thick film negative for sexual stages of malaria
- •Previous reaction to study drugs/known allergy to study drugs
- •Signs of severe malaria, including hyperparasitemia, defined as asexual parasitemia > 100,000 parasites / µL)
- •Signs of acute or chronic illness, including hepatitis
- •Use of other medications (with the exception of paracetamol and/or aspirin)
- •Consent not given
研究组 & 干预措施
SP-AQ only
Subjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days.
干预措施: Sulphadoxine-pyrimethamine (Drug)
SP-AQ only
Subjects will receive sulphadoxine-pyrimethamine (SP) as single dose and administered in combination with amodiaquine (AQ), which will be given once daily for 3 days.
干预措施: Amodiaquine (Drug)
SP-AQ plus PQ
Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
干预措施: Sulphadoxine-pyrimethamine (Drug)
SP-AQ plus PQ
Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
干预措施: 0.25 mg/kg primaquine (Drug)
SP-AQ plus PQ
Participants in this arm will receive SP-AQ in combination with a single low dose of primaquine at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
干预措施: Amodiaquine (Drug)
DP only
Participants in this arm will be treated with dihydroartemisinin-piperaquine (DP), which will be administered once a day for three days.
干预措施: Dihydroartemisinin-piperaquine (Drug)
DP plus MB
Study participants in this arm will receive DP as described above combined with once-daily methylene blue (MB) for 3 days, at 15 mg/kg/day (45 mg/kg total over 3 days).
干预措施: Methylene blue (Drug)
结局指标
主要结局
Mosquito infectivity assessed through membrane feeding assays
时间窗: 7 day
Infectivity will be measured by oocyst prevalence in dissected mosquitoes. Primary endpoint will be a comparison between mean of pretreatment infectivity (day 0) and infectivity at days 2 and 7 post first dose.
次要结局
- Safety measurements including hemoglobin and signs of hemolysis(42 days)
- Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine(24 hours)
- Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine(24 hours)
- Asexual parasite prevalence and density(42 days)
- Peak plasma concentration (Cmax) of primaquine(24 hours)
- Peak plasma concentration (Cmax) of methylene blue(24 hours)
- Area under the concentration curve (AUC) of methylene blue(24 hours)
- Elimination half-life (t1/2) of sulphadoxine-pyrimethamine(24 hours)
- Elimination half-life (t1/2) of dihydroartemisinin-piperaquine(24 hours)
- Elimination half life (t1/2) of primaquine(24 hours)
- Elimination half life (t1/2) of methylene blue(24 hours)
- Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine(24 hours)
- Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine(24 hours)
- Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms(1 hour)
- Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods.(42 days)
- Area under the concentration curve (AUC) of primaquine.(24 hours)