Adjunctive Ivermectin Mass Drug Administration for Malaria Control on the Bijagos Archipelago of Guinea Bissau: A Cluster-randomized Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 入组人数
- 24,000
- 试验地点
- 1
- 主要终点
- Prevalence of infection with Plasmodium falciparum
研究概览
简要总结
This is a cluster-randomized placebo-controlled clinical trial to evaluate the additive benefit of Ivermectin (IVM) (or Placebo) mass drug administration (MDA) to dihydroartemisinin-piperaquine (DP) MDA for malaria control in a moderate to low malaria-endemic setting as an adjunctive strategy to existing programmatic malaria control measures. The regime of DP and IVM will target both human reservoirs of Plasmodium falciparum and the Anopheles gambiae vector respectively, with the aim of interrupting transmission. The trial will be conducted on the Bijagos Archipelago, where islands (clusters) will be randomised to receive seasonal DP and IVM or DP and Placebo MDA. The primary outcome will be the prevalence of infection with Plasmodium falciparum in all age groups detected by nucleic acid amplification testing during the peak malaria transmission season after two years of intervention.
详细描述
The objectives of this trial are
- To evaluate the impact of adjunctive IVM to DP MDA on malaria transmission in communities with high ITN coverage.
- To evaluate the impact of IVM MDA on An. gambiae population density and age-structure.
- To evaluate the impact of IVM MDA on the prevalence of co-endemic IVM-susceptible Neglected Tropical Diseases (lymphatic filariasis, soil transmitted helminths and scabies)
- To evaluate acceptability, feasibility and access to MDA as a strategy for malaria control and to identify the most acceptable way of achieving and sustaining high coverage MDA with IVM and DP.
This cluster-randomized placebo-controlled trial has two arms. A total of 24 clusters will be randomly assigned to receive DP + IVM MDA or DP+ Placebo MDA using computer-generated random numbers. To mitigate against contamination effects, the majority of clusters will be separate islands and will be separated by distances greater than 2km. On the two islands that are divided (each into two clusters), a buffer zone of 2km between each cluster will be ensured. The total population of the archipelago is 24,000. The investigators will ensure balance between trial arms with respect to population size, baseline Plasmodium falciparum prevalence and access to health care. All clusters will receive the standard programmatic malaria control interventions implemented by the National Malaria Control Programme which includes insecticide-treated nets (ITN), intermittent preventative treatment in pregnancy (IPTp), seasonal malarial chemoprophylaxis (SMC) for children aged 3-59 months and case diagnosis and treatment (CDT) with Artemether-lumefantrine.
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)
盲法说明
An independent statistician will randomize the clusters to DP+IVM or DP+Placebo. The Placebo is identical in size, shape and colour and packaging. An independent pharmacist at Medical Research Council Unit The Gambia @ London School of Hygiene and Tropical Medicine will label the IVM and Placebo according to the statistician's designation and maintain the masking from all other investigators. Specifically generated masking codes will be generated and saved in three separate encrypted locations securely. Only the statistician and the pharmacist will have access to the encryption key.
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age over six months to receive dihydroartemisinin-piperaquine
- •Height over 90cm or weight over 15kg to receive ivermectin or placebo
- •Willingness to adhere to trial procedures
- •Individual written, informed consent from the participant or parent/guardian in the case of participants below the age of 18 years (and assent in young people between the ages of 12 and 17 years of age)
排除标准
- •Known severe chronic illness (AIDS, Tuberculosis, chronic malnutrition)
- •Known hypersensitivity to either dihydroartemisinin-piperaquine or ivermectin
- •Pregnancy (any trimester) and breastfeeding (for ivermectin (or placebo)) and pregnancy (first trimester only) (for dihydroartemisinin-piperaquine)
- •Travel to a Loa loa endemic country (eg Central African Republic) (for ivermectin (or placebo))
- •Concomitant drugs that influence cardiac function or affect the corrected QT interval (for dihydroartemisinin-piperaquine)
研究组 & 干预措施
Ivermectin Mass Drug Administration
Ivermectin and Dihydroartemisinin-piperaquine MDA will be given to all eligible participants in each cluster (island) in addition to the standard national malaria control programme interventions.
干预措施: Ivermectin (Drug)
Ivermectin Mass Drug Administration
Ivermectin and Dihydroartemisinin-piperaquine MDA will be given to all eligible participants in each cluster (island) in addition to the standard national malaria control programme interventions.
干预措施: Dihydroartemisinin-piperaquine (Drug)
Placebo Mass Drug Administration
Placebo and Dihydroartemisinin-piperaquine MDA will be given to all eligible participants in each cluster (island) in addition to the standard national malaria control programme interventions.
干预措施: Placebo (Drug)
Placebo Mass Drug Administration
Placebo and Dihydroartemisinin-piperaquine MDA will be given to all eligible participants in each cluster (island) in addition to the standard national malaria control programme interventions.
干预措施: Dihydroartemisinin-piperaquine (Drug)
结局指标
主要结局
Prevalence of infection with Plasmodium falciparum
时间窗: 2 years
Prevalence of infection with Plasmodium falciparum in all age groups estimated using a cross-sectional survey sample conducted during peak transmission season after 2 years of intervention
次要结局
- Vector parous rate(7-14 days post-MDA)
- Incidence of clinical malaria (Active Case Detection)(For six months during the malaria transmission season)
- Prevalence of infection with Plasmodium falciparum(1 year)
- Vector density(For six months during the malaria transmission season)
- Incidence of clinical malaria (Passive Case Detection)(For six months during the malaria transmission season)
- Vector species composition(For six months during the malaria transmission season)
- MDA coverage estimates(During MDA in year 1 and year 2)
- Age-adjusted prevalence of recent exposure to Plasmodium falciparum(Peak transmission season at 1 year and 2 years)
- Prevalence of exposure to Anopheles exposure(Peak transmission season at 1 year and 2 years)
- Vector sporozoite rates(For six months during the malaria transmission season)
- Prevalence of Ivermectin-susceptible Neglected Tropical Diseases (NTDs)(2 years)
- Prevalence of resistance to artemisinin and partner drugs in humans(Peak transmission season at 1 year and at 2 years)