A Four-arm Trial Comparing Artemether-lumefantrine With or Without Single-dose Primaquine and Sulphadoxine-pyrimethamine/Amodiaquine With or Without Single-dose Tafenoquine to Reduce P. Falciparum Transmission 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
- Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7)
研究概览
简要总结
The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artemether-lumefantrine (AL) with and without a single dose of 0.25mg/kg primaquine (PQ) and sulfadoxine-pyrimethamine with amodiaquine (SPAQ) with and without single dose of 1.66mg/kg tafenoquine (TQ). Outcome measures will include infectivity to mosquitoes at 2, 5 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.
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
- 10 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 10 years and ≤ 50 years
- •G6PD-normal defined by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test
- •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
- •Hemoglobin ≥ 10 g/dL
- •Individuals weighing < = 80 kg
- •No evidence of acute severe or chronic disease
- •Written, informed consent
排除标准
- •Women who are pregnant or lactating (tested at baseline). Urine and/or serum pregnancy testing (β-hCG) will be used.
- •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 (except for paracetamol and/or aspirin)
- •Use of antimalarial drugs over the past 7 days (as reported by the participant)
- •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.
- •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
Artemether-lumefantrine (AL)
Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days.
干预措施: Artemether-lumefantrine (Drug)
AL with 0.25mg/kg primaquine (PQ)
Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of AL treatment.
干预措施: Artemether-lumefantrine (Drug)
AL with 0.25mg/kg primaquine (PQ)
Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of AL treatment.
干预措施: Primaquine Phosphate (Drug)
Sulphadoxine-pyrimethamine with amodiaquine (SPAQ)
Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days.
干预措施: Sulphadoxine-pyrimethamine with amodiaquine (Drug)
SPAQ with 1.66mg/kg tafenoquine (TQ)
Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days and a single dose of 1.66mg/kg tafenoquine (TQ) on the first day of SPAQ treatment.
干预措施: Sulphadoxine-pyrimethamine with amodiaquine (Drug)
SPAQ with 1.66mg/kg tafenoquine (TQ)
Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days and a single dose of 1.66mg/kg tafenoquine (TQ) on the first day of SPAQ treatment.
干预措施: Tafenoquine (Drug)
结局指标
主要结局
Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7)
时间窗: 3 days (days 0, 2 and 7): 7 day span
Within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and AL-PQ arms, and day 7 post-treatment in the SPAQ and SPAQ-TQ.
次要结局
- Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Mosquito infection rate assessed through membrane feeding assays(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Mosquito infection density assessed through membrane feeding assays(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Asexual/sexual stage parasite prevalence(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Haemoglobin density(8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Human infectivity to locally reared mosquitoes assessed through membrane feeding assays(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Gametocyte infectivity(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Asexual/sexual stage parasite density(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Sexual stage parasite sex ratio(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Sexual stage parasite circulation time(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Sexual stage parasite area under the curve (AUC)(7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Change in haemoglobin density(8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Methaemoglobin density(8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28))
- Incidence of adverse events(8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)
- Change in methaemoglobin density(8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span)