Single Low Dose Tafenoquine to Reduce P. Falciparum Transmission in Mali (NECTAR2)
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
- Change in mosquito infectivity assessed through membrane feeding assays (day 7)
研究概览
简要总结
The purpose of this study is to assess the gametocytocidal and transmission reducing activity of dihydroartemisinin-piperaquine (DP) with and without various low doses of tafenoquine (TQ; 1.66mg/kg, 0.83mg/kg, or 0.415mg/kg). Outcome measures will include infectivity to mosquitoes at 2 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density.
详细描述
Full protocol available 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)
盲法说明
This is a single blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded, but no placebo will be used. The study pharmacist will be unblinded and responsible for randomisation and treatment administration.
入排标准
- 年龄范围
- 12 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 12 years and ≤ 50 years
- •Glucose 6 phosphate dehydrogenase (G6PD) normal status defined by Carestart rapid diagnostic test or the G6PD qualitative test (OSMMR2000)
- •Absence of symptomatic falciparum malaria, defined by fever on enrolment
- •Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/µL (i.e. ≥ gametocytes recorded in the thick film against 500 white blood cells)
- •Absence of other non-P. falciparum species on blood film
- •No allergies to study drugs
- •No 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 acute severe or chronic disease
- •Written, informed consent
排除标准
- •Age < 12 years or > 50 years
- •Women who are pregnant or lactating
- •Blood thick film negative for sexual stages of malaria
- •Detection of a non-P. falciparum species by microscopy
- •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
- •The use of other medication (with the exception of paracetamol and/or aspirin)
- •Consent not given
- •G6PD-deficiency by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test
- •Use of antimalarial drugs over the past 7 days (as reported by the participant)
- •The use of other medication (with the exception of paracetamol and/or aspirin)
- •Clinically significant illness (intercurrent illness e.g. pneumonia, pre-existing condition e.g. renal disease, malignancy or conditions that may affect absorption of study medication e.g. severe diarrhea or any signs of malnutrition as defined clinically)
- •Signs of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child Pugh stage B or C)
- •Signs, symptoms or known renal impairment
- •Clinically significant abnormal laboratory values as determined by history, physical examination or routine blood chemistries and hematology values (laboratory guideline values for exclusion are hemoglobin < 10 g/dL, platelets < 50,000/μl, White Blood Cell count (WBC) < 2000/μl, serum creatinine >2.0mg/dL, or ALT or AST more than 3 times the upper limit of normal for age.
- •Family history of diseases leading to QT prolongation or recent treatment with drugs linked to QT prolongation
- •Blood transfusion in the last 90 days.
- •Consistent with the long half-life of tafenoquine, effective contraception should be continued for 5 half-lives (3 months) after the end of treatment.
- •History of psychiatric disorders
研究组 & 干预措施
Dihydroartemisinin-Piperaquine (DP)
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a low dose of 1.66mg/kg, 0.83mg/kg, or 0.415mg/kg. Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Dihydroartemisinin/Piperaquine (Drug)
DP with 0.415mg/kg Tafenoquine (TQ)
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a single dose of 0.415mg/kg Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Dihydroartemisinin/Piperaquine (Drug)
DP with 0.415mg/kg Tafenoquine (TQ)
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a single dose of 0.415mg/kg Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Tafenoquine 100mg [Arakoda] (Drug)
DP with 0.83 mg/kg TQ
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a single dose of 0.83mg/kg Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Dihydroartemisinin/Piperaquine (Drug)
DP with 0.83 mg/kg TQ
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and a single dose of 0.83mg/kg Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Tafenoquine 100mg [Arakoda] (Drug)
DP with 1.66mg/kg TQ
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and single dose of 1.66mg/kg Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Dihydroartemisinin/Piperaquine (Drug)
DP with 1.66mg/kg TQ
Subjects will receive Dihydroartemisinin-Piperaquine (DP) once daily for 3 days, and single dose of 1.66mg/kg Tafenoquine (TQ) on the first date of DP treatment.
干预措施: Tafenoquine 100mg [Arakoda] (Drug)
结局指标
主要结局
Change in mosquito infectivity assessed through membrane feeding assays (day 7)
时间窗: 2 days (Days 0 & 7): 7 day span
The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 7 post feed, compared to baseline
次要结局
- Mosquito infection density assessed through membrane feeding assays(4 days (Days 0, 2, 7 & 14): 14 day span)
- Mosquito infection prevalence assessed through membrane feeding assays(4 days (Days 0, 2, 7 & 14): 14 day span)
- Haemoglobin density(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Blood creatinine level(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Asexual/sexual stage parasite prevalence(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Change in mosquito infectivity assessed through membrane feeding assays (days 2 and 14)(3 days (Days 0, 2, & 14): 14 day span)
- Human infectivity assessed through membrane feeding assays(4 days (Days 0, 2, 7 & 14): 14 day span)
- Methmoglobin density(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Asexual/sexual stage parasite density(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Asexual/sexual stage parasite circulation time(28 days)
- Incidence of adverse events(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Aspartate transaminase (AST)/alanine transaminase (ALT) ratio(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)
- Asexual/sexual stage parasite area under the curve (AUC)(28 days)
- Sexual stage parasite sex ratio(7 days (Days 0, 1, 2, 7, 14, 21 & 28): 28 day span)