Applying Wolbachia to Eliminate Dengue (AWED)

June 5, 2020 updated by: Riris Andono Ahmad, Gadjah Mada University

Applying Wolbachia to Eliminate Dengue (AWED): A Non-blinded Cluster Randomised Controlled Trial to Assess the Efficacy of Wolbachia-infected Mosquito Deployments to Reduce Dengue Incidence in Yogyakarta, Indonesia

This cluster randomised trial will evaluate the efficacy of Wolbachia-infected Aedes aegytpi mosquitoes in reducing dengue cases in Yogyakarta City, Indonesia

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Primary objective:

To assess the efficacy of community-based deployments of Wolbachia-infected Aedes aegypti mosquitoes in reducing the incidence of symptomatic, virologically-confirmed dengue cases of any severity in Yogyakarta residents aged 3-45 years in release areas, relative to non-release areas.

Secondary objectives:

  • To measure the efficacy of the Wolbachia method against each of the four DENV serotypes.
  • To measure the efficacy of the Wolbachia method in reducing the incidence of symptomatic virologically confirmed Zika virus and chikungunya virus infection in release areas, relative to non-release areas
  • To quantify the level of human mobility within Yogyakarta City, and estimate the proportion of residents' exposure time that they spend outside the treatment arm to which they were randomised
  • To determine whether community-based deployment of Wolbachia-infected Ae. aegypti mosquitoes reduces the abundance of wild-type Ae. aegypti adults, or alternatively, alters the abundance of adults from Aedes species other than Ae. aegypti (e.g. Ae. albopictus)

Study setting:

The study will be conducted in Yogyakarta City and Bantul District, both located in the province of Yogyakarta Special Region, Indonesia.The study site is 26 km2 in size, including 24 km2 within Yogyakarta City, and 2km2 in the adjacent Bantul District. The total population of the study area is approximately 350,000.

Study design:

A cluster randomised trial with a test-negative design will be conducted. The study site will be divided into 24 clusters. The intervention will be allocated using constrained block randomisation with a parallel 1:1 assignment of intervention and control.

The intervention is the deployment of Wolbachia-infected Aedes aegypti mosquitoes. Wolbachia deployments will be conducted in intervention clusters with the aim of achieving Wolbachia establishment (>80% mean Wolbachia prevalence in trapped mosquitoes) throughout intervention areas within one year.

The impact of Wolbachia deployments on dengue incidence will be assessed by comparing the exposure distribution (probability of living in a Wolbachia-treated area) among virologically-confirmed dengue cases presenting to a network of public primary clinics (Puskesmas), against the exposure distribution among patients with febrile illness of non-arboviral aetiology presenting to the same network of clinics in the same temporal windows. Dengue cases and arbovirus-negative controls will be sampled concurrently from within the population of patients presenting with febrile illness to the study clinic network, with case or control status classified retrospectively based on the results of laboratory diagnostic testing.

A re-estimation of sample size requirements was conducted in January 2019 after one year of recruitment. The initial power calculation used 1000 dengue cases and 4000 non-dengue controls allocated to each cluster based on historical proportions of dengue cases and other febrile illnesses, assuming no variation in the proportion of cases by cluster. This method was found to overestimate power for small samples by not taking into account randomness in the sampling. The sample size re-estimation included power estimates for 200, 400, 600, 800 and 1000 dengue cases with 4 times as many controls allocated to each cluster by sampling from a multinomial distribution, which incorporated added randomness by allowing the proportion of cases allocated to each cluster to vary across simulations. The re-estimation found that 400 dengue cases plus four times as many controls would be sufficient to detect a 50% reduction in dengue incidence with 80% power.

Participant selection:

Participants will be enrolled from within the population of patients presenting with undifferentiated fever of 1-4 days duration, to one of the participating local health clinics (Puskesmas).

All patients meeting the inclusion criteria will be invited to participate in the study. From baseline historical data we expect approximately 5000 participants per annum to be enrolled.

Enrolment will continue for up to 36 months.

Analysis plan:

Permutation tests and standard regression models will be used to estimate the relative risk of dengue in Wolbachia-treated versus untreated clusters, accounting for the non-independence of study participants resident in the same intervention cluster, and temporal matching of dengue cases and test-negative controls.

The intention-to-treat analysis will consider Wolbachia exposure as binary depending on the allocation of the cluster of residence.

The per-protocol analysis will consider Wolbachia exposure as a continuous weighted index based on Wolbachia prevalence in trapped mosquitoes in the cluster of residence, either with or without weighting for time spent in other clusters visited during the ten days prior to illness onset.

Study Type

Interventional

Enrollment (Actual)

8173

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • DIY
      • Yogyakarta, DIY, Indonesia, 55281
        • Faculty of Medicine, Universitas Gadjah Mada

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Fever (either self-reported or objectively measured, e.g. (tympanic membrane temperature ≥38oC)) of 1-4 days duration, and where onset was prior to the day of presentation
  • Aged between 3-45 years old
  • Resided in the study area every night for the 10 days preceding illness onset

Exclusion Criteria:

  • Localising features suggestive of a specific diagnosis other than an arboviral infection e.g. severe diarrhea, otitis, pneumonia
  • Prior enrollment in the study within the previous 4 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention arm
Deployment of Wolbachia-infected Aedes aegypti mosquitoes
Biological: Wolbachia-infected Aedes aegypti mosquitoes
Deployment of Wolbachia-infected Aedes aegypti mosquitoes
Other: standard practice dengue control
standard practice dengue control activities conducted by dengue control program
Other: Comparison arm
Standard practice dengue control activities
Other: standard practice dengue control
standard practice dengue control activities conducted by dengue control program

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative risk of dengue in Wolbachia-treated versus untreated clusters
Time Frame: Up to 36 months participant enrolment
Symptomatic, virologically-confirmed dengue virus (DENV) infection of any severity
Up to 36 months participant enrolment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative risk of serotype-specific dengue in Wolbachia-treated versus untreated clusters
Time Frame: Up to 36 months participant enrolment
Symptomatic, virologically-confirmed serotype-specific DENV infection of any severity.
Up to 36 months participant enrolment
Relative risk of Zika in Wolbachia-treated versus untreated clusters
Time Frame: Up to 36 months participant enrolment
Symptomatic, virologically-confirmed Zika virus (ZIKV) infection of any severity.
Up to 36 months participant enrolment
Relative risk of Chikungunya in Wolbachia-treated versus untreated clusters
Time Frame: Up to 36 months participant enrolment
Symptomatic, virologically-confirmed Chikungunya virus (CHIKV) infection of any severity.
Up to 36 months participant enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gadjah Mada University

Collaborators

Monash University
The Tahija Foundation

Investigators

  • Principal Investigator: Adi Utarini, MD, PhD, Faculty of Medicine, Universitas Gadjah Mada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 8, 2017

Primary Completion (Actual)

March 18, 2020

Study Completion (Actual)

April 8, 2020

Study Registration Dates

First Submitted

February 14, 2017

First Submitted That Met QC Criteria

February 14, 2017

First Posted (Actual)

February 16, 2017

Study Record Updates

Last Update Posted (Actual)

June 9, 2020

Last Update Submitted That Met QC Criteria

June 5, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UGM_KE/FK/105/EC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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