A Five-arm Trial Comparing Artesunate-amodiaquine and Artemether-lumefantrine-amodiaquine With or Without Single-dose Primaquine to Reduce P. Falciparum Transmission in Mali
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in mosquito infection rate assessed through membrane feeding assays
研究概览
简要总结
The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine-amodiaquine (ALAQ) with and without a single dose of 0.25mg/kg primaquine (PQ). Outcome measures will include infectivity to mosquitoes at 2, 7 and 14 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
- •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
- •Haemoglobin ≥ 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, such as sudden high fevers, shaking or severe sore throat or ulcers in the mouth during treatment with Amodiaquine
- •Current eye disease with retinal damage
- •Signs of severe malaria, including hyperparasitaemia (defined as asexual parasitaemia > 100,000 parasites / µL)
- •Signs of acute or chronic illness, including hepatitis
- •The use of other medication (except for paracetamol and/or aspirin), including antacids, other medicines used to treat malaria, abnormal heart rhythm, depression or mental illness or HIV/AIDS, and medicines that have antibiotic/antifungal properties
- •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 or HIV/AIDS, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhoea 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 haematology values (laboratory guideline values for exclusion are haemoglobin < 10 g/dL, platelets < 50,000/μl, White Blood Cell count (WBC) < 2000/μl, serum creatinine >2.0mg/dL, or ALT more than 3 times the upper limit of normal for age.
- •Blood transfusion in the last 90 days.
- •Known Electrocardiogram (ECG) corrected QT interval of more than 450 ms
- •Documented or self-reported history of cardiac conduction problems
- •Documented or self-reported history of epileptic seizures
研究组 & 干预措施
artesunate-amodiaquine (ASAQ)
Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days.
干预措施: Artesunate-amodiaquine combination (Drug)
ASAQ with 0.25mg/kg primaquine (PQ)
Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ASAQ treatment.
干预措施: Artesunate-amodiaquine combination (Drug)
ASAQ with 0.25mg/kg primaquine (PQ)
Subjects will receive artesunate-amodiaquine (ASAQ) daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ASAQ treatment.
干预措施: Primaquine Phosphate (Drug)
Artemether-Lumefantrine (AL)
Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days.
干预措施: Artemether-lumefantrine (Drug)
Artemether-Lumefantrine-Amodiaquine (ALAQ)
Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days.
干预措施: Artemether-lumefantrine (Drug)
Artemether-Lumefantrine-Amodiaquine (ALAQ)
Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days.
干预措施: Amodiaquine (Drug)
Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)
Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ALAQ treatment.
干预措施: Primaquine Phosphate (Drug)
Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)
Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ALAQ treatment.
干预措施: Artemether-lumefantrine (Drug)
Artemether-Lumefantrine-Amodiaquine (ALAQ) with 0.25 mg/kg primaquine (PQ)
Subjects will receive artemether-lumefantrine (AL) and amodiaquine (AQ) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of ALAQ treatment.
干预措施: Amodiaquine (Drug)
结局指标
主要结局
Change in mosquito infection rate assessed through membrane feeding assays
时间窗: 2 days (days 0 and 2): 3 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 ASAQ, ASAQ-PQ, AL, ALAQ and ALAQ-PQ arms.
次要结局
- Sexual stage parasite circulation time(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Haemoglobin density(7 days (day 0, day 1, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Change in haemoglobin density(7 days (day 0, day 1, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Gametocyte infectivity(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Asexual/sexual stage parasite prevalence(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Sexual stage parasite area under the curve (AUC)(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Incidence of adverse events(7 days (day 0, day 1, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Mosquito infection rate assessed through membrane feeding assays(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Human infectivity to locally reared mosquitoes assessed through membrane feeding assays(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Mosquito infection density assessed through membrane feeding assays(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Asexual/sexual stage parasite density(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)
- Sexual stage parasite sex ratio(6 days (day 0, day 2, day 7, day 14, day 21, day 28): 28 day span)