A Phase III Cluster-randomized, Open-label, Clinical Trial to Study the Safety and Efficacy of Ivermectin Mass Drug Administration to Reduce Malaria Transmission in Two African Settings
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 48,145
- 试验地点
- 2
- 主要终点
- To determine the safety (in humans) and efficacy of ivermectin MDA, administered to humans, or humans and livestock simultaneously (only in Mozambique) for the prevention of malaria.
研究概览
简要总结
The BOHEMIA program consists of a combination of studies organized around a central community prevention mass drug administration protocol and four sub-studies (i.e.; social science, entomology, health economics, and environmental), each written as an individual protocol. The protocol is central but used in two separate, individually powered trials in Mozambique and Kenya. The trials have been powered on the efficacy outcome and designed to meet the requirements of World Health Organization's (WHO) preferred product characteristics (PPC) for endectocides.
详细描述
WHO's PPC states that the desired efficacy of an endectocide as stand-alone insecticide in areas of high to moderate transmission is at least 20% reduction in the incidence of clinical malaria (as primary outcome) and incidence of infection (as secondary outcome) in children under 5 years old (the highest incidence age-group in areas with high-transmission), lasting for at least 1 month following a single regimen. Assessing this effect requires a cluster-randomized design with meticulous follow-up of a cohort of children for efficacy and the whole exposed population for safety outcomes, which is the design selected for the BOHEMIA trials.
Two BOHEMIA cluster randomized trials will be carried out in Mozambique (Southern Africa) and Kenya (Eastern Africa). These sites encompass different transmission dynamics that increase the generalizability of results, namely: (a) a gradient of malaria transmission: moderate in Kenya and very high in Mozambique, (b) different species composition of vector population, (c) different rain patterns and environmental conditions, and (d) different livestock species and human/livestock ratios (in Mozambique).
Population:
Co-primary objectives are determined in different populations. Efficacy is primarily determined in a pediatric active cohort (children under 5 years of age in Mozambique and 5-15 years in Kenya), and safety is determined in anyone who receives the drug. Pregnant women and children under 15 kgs are not eligible for treatment.
Treatment Groups:
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
- None
盲法说明
Open label, assessor-blinded
入排标准
- 年龄范围
- 1 Week 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Albendazole
The albendazole group will receive a single dose of 400 mg, given once a month for three months. Generic products will be used in both countries, the final product will be GMP certified and fully bioequivalent with GSK's Albenza®. Bendex (CIPLA) in Mozambique and G-Abzole (Guilin) in Kenya.
干预措施: Albendazole Pill (Drug)
Ivermectin human
The ivermectin group will receive a single dose of 400 mcg/kg, given once a month for three months. Product to be used is Stromectol (Merck) in Mozambique and Ivermectin 3mg USP (Edenbridge) in Kenya.
干预措施: Ivermectin Pill (Drug)
Ivermectin human and livestock (Mozambique only)
The ivermectin group will receive a single dose of 400 mcg/kg, given once a month for three months. Product to be used is Stromectol (Merck). For livestock, locally registered veterinary injectable ivermectin at 1% will be used.
干预措施: Ivermectin Pill (Drug)
Ivermectin human and livestock (Mozambique only)
The ivermectin group will receive a single dose of 400 mcg/kg, given once a month for three months. Product to be used is Stromectol (Merck). For livestock, locally registered veterinary injectable ivermectin at 1% will be used.
干预措施: Ivermectin Injectable Product (Drug)
结局指标
主要结局
To determine the safety (in humans) and efficacy of ivermectin MDA, administered to humans, or humans and livestock simultaneously (only in Mozambique) for the prevention of malaria.
时间窗: 6 months
Safety: The safety endpoint is determined by anyone who receives the drug. Rate of adverse events (AEs) and serious adverse events (SAEs) and difference between ivermectin and albendazole.
次要结局
- To assess the relationship between malaria incidence in children (under 5 years in Mozambique and 5-15 years in Kenya) and community prevalence at the peak of the malaria season.(6 months)
- To assess the efficacy of the intervention using complementary methods (efficacy).(6 months)
- To assess the safety of the intervention with complementary methods (safety).(12 months)
- To assess the PK of the proposed ivermectin dose/regime in its relationship with efficacy and safety outcomes (efficacy and safety).(72 hours)
- To assess the impact of ivermectin MDA at the proposed regimen on the prevalence of selected ectoparasitic NTDs (efficacy on NTDs and acceptability).(6 months)
- To assess the relationship between active and passive surveillance for malaria at health facility (only Mozambique).(18 months)
- To assess the accuracy for malaria diagnosis of two the different malaria rapid diagnostic tests (RDTs) used in comparison to Polymerase Chain Reaction (PCR) (Mozambique).(6 months)
- To assess the accuracy for malaria diagnosis of two the different malaria rapid diagnostic tests (RDTs) used in comparison to PCR (Mozambique).(6 months)