Clinical trial NCT06894901: Impact of IIT-SIT on Dengue Clusters
Official title: Assessing the Efficacy of Incompatible Insect Technique Coupled with Sterile Insect Technique (IIT-SIT) to Manage Large Dengue Clusters: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dengue
Lead sponsor: National Environment Agency, Singapore
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Health, Singapore
First posted: 2025-03-25
Enrollment: 900
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized controlled trial aims to evaluate the efficacy of Wolbachia-infected male mosquitoes combined with sterile insect technique (IIT-SIT) to mitigate active dengue transmission in Singapore.

Detailed description: Aedes-borne diseases are expected to increase in geographical coverage and intensity due to climate change and rapid urbanization. It has been demonstrated that Wolbachia-mediated incompatible insect technique coupled with sterile insect technique (IIT-SIT) is highly effective in suppressing Aedes populations and subsequently reducing dengue risk. However, the efficacy of the tool in mitigating ongoing transmission is unknown.

The researchers outline a randomized controlled trial to be conducted in high-rise public housing estates in Singapore to assess the efficacy of IIT-SIT to mitigate active dengue transmission. Specifically, the study will determine whether the release of male Wolbachia-infected Aedes aegypti mosquitoes can curtail the growth of dengue clusters, defined operationally by the Singapore National Environment Agency (NEA) as two or more reported dengue cases within a 150-meter radius and with illness onset dates within 14 days of each other. This study will randomize eligible clusters into intervention/control arms in real-time. Clusters assigned to the intervention arm will receive IIT-SIT treatment until cluster extinction (i.e. when no further cases are linked to the cluster). This trial closely mimics how IIT-SIT could be used as an additional tool for outbreak management, by treating areas with active dengue transmission in real-time. Conventional vector control measures will be carried out as per NEA's usual outbreak management practices in both intervention and control clusters. The intervention efficacy will be estimated through two primary endpoints: (1) probability of cluster extinction, as estimated from the time-to-cluster extinction among intervention versus control clusters; and (2) final size of the dengue cluster, as estimated by the difference in the final number of dengue cases in intervention versus control clusters.

This study will provide evidence from a randomized controlled trial for the efficacy of IIT-SIT in curbing ongoing transmission and provide an epidemiological basis for integrating IIT-SIT into the existing arsenal of outbreak management tools. The trial will assess the technology's feasibility for operationalization, and identify difficulties in implementation prior to larger-scale use for outbreak control.

Eligibility criteria: Eligible dengue clusters will be limited to public housing estates and with at least 10 dengue cases comprising that dengue cluster before allocation into intervention or control arms. The selected clusters will be in areas with relatively high sector-level GAI of at least 0.2 at the time of the 10th reported case. Additionally, the first 10 cases must be reported within 30 days of the first case. Additionally, clusters must be in areas which have never experienced Wolbachia-Aedes releases and at least 700 m away from existing Wolbachia-Aedes release areas.

Primary outcomes:
measure: Impact of male Wolbachia-Aedes deployments on the time to cluster extinction
timeFrame: Up to 3 years
measure: Impact of male Wolbachia-Aedes deployments on final cluster size, as measured by the difference in final cluster size between arms
timeFrame: Up to 3 years
Secondary outcomes:
measure: Impact of male Wolbachia-Aedes deployments on the prevalence of Ae. aegypti/Ae. albopictus mosquitoes
timeFrame: Up to 3 years
measure: Impact of male Wolbachia-Aedes deployments on dengue risk in clusters, measured by odds ratio of Wolbachia exposure distribution among laboratory-confirmed reported dengue cases compared to test-negative controls
timeFrame: Up to 3 years
measure: Impact of male Wolbachia-Aedes deployments on the individual level reproduction number
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National Environment Agency
Study officials:
affiliation: Environmental Health Institute
name: Lee Ching Ng Group Director (Environmental Health Institute), PhD
role: PRINCIPAL_INVESTIGATOR
References: