Trials. 2022 Aug 9;23(1):640. doi: 10.1186/s13063-022-06555-8.
Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings.
METHODS/DESIGN: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a "fried-egg" design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5-14 years in Mali and 1-14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya.
Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic.
Zambia: ClinicalTrials.gov NCT04800055 . Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119 . Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565 . Registered on February 2, 2022.
长效杀虫蚊帐（LLINs）和室内滞留喷洒（IRS）针对夜间室内叮咬的蚊子，有效降低了非洲农村地区的疟疾传播，但需要额外的病媒控制工具来阻断传播。诱捕靶向糖饵（ATSBs）可诱捕并杀死蚊子，包括户外叮咬的蚊子。在马里，含有杀虫剂二噻农的诱捕靶向糖饵的部署与蚊子密度和寿命的大幅降低有关。这种有前景的干预措施对疟疾传播和发病率的影响现在需要在一系列传播环境中确定。
方法/设计：我们将在马里、肯尼亚和赞比亚进行三项类似的独立、开放标签、双臂、整群随机对照试验（cRCT），以确定诱捕靶向糖饵+普遍病媒控制与单独普遍病媒控制对临床疟疾的影响。试验将采用“煎蛋”设计，在每个群集的核心区域测量主要结局，以减少溢出效应。诱捕靶向糖饵群集的所有家庭结构都将收到两个诱捕靶向糖饵，但影响将在群集的核心区域进行测量。将采用受限随机化。主要结局是马里 5-14 岁儿童和肯尼亚和赞比亚 1-14 岁儿童的临床疟疾发病率。一个关键的次要结局是所有年龄段的疟疾寄生虫患病率。试验将包括 76 个群集（每组 38 个）在马里和每组 70 个（每组 35 个）在肯尼亚和赞比亚。试验旨在检测临床疟疾减少 30%，这需要在马里进行总共 3850 人年的随访，肯尼亚进行 1260 人年，赞比亚进行 1610 人年。这些样本量将使用马里的两个季节性 8 个月队列和赞比亚的两个季节性 6 个月队列来确定。在肯尼亚，全年都有传播，将使用四个 6 个月的队列（总共 24 个月的随访）。该设计允许在马里和赞比亚进行一次中期分析，在肯尼亚进行两次。
该设计的优势包括在具有不同传播模式和一系列病媒的多个研究地点使用，以提高外部有效性，每个试验点内有大量的群集，受限随机化，群集之间的分离以尽量减少研究臂之间的污染，以及适应性试验设计。内部有效性的威胁包括开放标签设计、研究臂之间污染的风险、研究臂之间协变量不平衡的风险、诱捕靶向糖饵站耐久性的变化以及 COVID-19 大流行可能导致的中断。
赞比亚：ClinicalTrials.gov NCT04800055. 于 2021 年 3 月 15 日注册。马里：ClinicalTrials.gov NCT04149119. 于 2019 年 11 月 4 日注册。肯尼亚：ClinicalTrials.gov NCT05219565. 于 2022 年 2 月 2 日注册。
