Efficacy and Safety of High-dose Ivermectin for Reducing Malaria Transmission: A Dose Finding Study (IVERMAL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 141
- 试验地点
- 1
- 主要终点
- Mosquito survival
研究概览
简要总结
In western Kenya the prevalence of malaria in <5 year olds has fallen from 70% in 1997 to 40% in 2008, where it has now stagnated. Innovative approaches are needed to continue towards elimination. Ivermectin is a broad spectrum antiparasitic endectocide widely used for the control of onchocerciasis and lymphatic filariasis at a dose of 150-200 mcg/kg. Ivermectin at this dose has a potent, but short-lived effect for 6-11 days on mosquito survival, egg-laying, and parasite sporogony. Higher doses are needed to prolong its mosquitocidal effects. Previous studies have shown ivermectin is very well tolerated and safe even up to 2,000 mcg/kg. This dose finding study will evaluate the transmission blocking effect of high-dose ivermectin to define the optimal dose for future use of ivermectin in combination with artemisinin-based combination therapy (ACT) for mass drug administration (MDA). It explores a research question of global relevance. A prolonged transmission blocking effect of ivermectin could have substantial consequences for malaria control in the next decades. The results are expected to inform national malaria control programs in malaria endemic countries, to inform WHO guidelines, and to contribute to the regulatory process.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic, uncomplicated Plasmodium falciparum infection
- •Positive malaria microscopy or malaria RDT (pLDH)
- •Age: 18-50 years
- •Provide written informed consent
- •Agree to be able to travel to clinic on days: 1, 2, 7, 10, 14, 21, and 28
排除标准
- •Signs or symptoms of severe malaria
- •Unable to provide written informed consent
- •For women: pregnancy or lactation
- •Hypersensitivity to ivermectin or DP
- •QTc >460 ms on ECG
- •Body Mass Index (BMI) below 16 or above 32 kg/m2
- •Haemoglobin concentration below 9 g/dL
- •Taken ivermectin in the last month
- •Taken dihydroartemisinin-piperaquine in the last 12 weeks
- •Loa loa as assessed by travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan
- •History and/or symptoms indicating chronic illness
- •Current use of tuberculosis or anti-retroviral medication
- •Previously enrolled in the same study
研究组 & 干预措施
placebo
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day.
干预措施: placebo (Drug)
placebo
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: placebo 600 mcg/kg/day.
干预措施: dihydroartemisinin-piperaquine (Drug)
ivermectin 300 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 300 mcg/kg/day and placebo 300 mcg/kg/day.
干预措施: ivermectin (Drug)
ivermectin 300 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 300 mcg/kg/day and placebo 300 mcg/kg/day.
干预措施: placebo (Drug)
ivermectin 300 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 300 mcg/kg/day and placebo 300 mcg/kg/day.
干预措施: dihydroartemisinin-piperaquine (Drug)
ivermectin 600 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day.
干预措施: ivermectin (Drug)
ivermectin 600 mcg/kg
Standard 3-day course of dihydroartemisinin-piperaquine, plus once a day for 3 days: ivermectin 600 mcg/kg/day.
干预措施: dihydroartemisinin-piperaquine (Drug)
结局指标
主要结局
Mosquito survival
时间窗: Survival of mosquitoes at 14 days after feeding on blood taking from study participants who started the 3-day ivermectin and DP regimen 7 days earlier.
次要结局
- Peak plasma Concentration (Cmax) of ivermectin(Up to day 28.)
- Peak plasma Concentration (Cmax) of piperaquine(Up to day 28.)
- Mosquito survival(Survival of mosquitoes at each day up to day 21 or 28 after each feeding experiments performed at 0, 2 day+4h, 10, 14, 21, 28 days after start of treatment.)
- Tolerability as assessed by adverse events reported in a general toxicity questionnaire(Up to day 28.)
- Area under the plasma concentration versus time curve (AUC) of ivermectin(Up to day 28.)
- CNS adverse events(Up to day 28.)
- Number of patients with malaria clinical and parasitological treatment response(Up to day 28.)
- Haemoglobin concentrations(Up to day 28.)
- Mydriasis quantitated by pupillometry(Up to day 28.)
- Area under the plasma concentration versus time curve (AUC) of piperaquine(Up to day 28.)
- Serious adverse events(Up to day 28.)
- QTc interval(At 52 hours.)