Home » Trials » SLCTR/2022/018


A cluster randomized, placebo control trial to evaluate the efficacy of a spatial repellent (Mosquito ShieldTM) against Aedes-borne virus infection among children >= 4–16 years of age in the Gampaha District, Sri Lanka

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SLCTR Registration Number

SLCTR/2022/018


Date of Registration

01 Jul 2022

The date of last modification

Jul 01, 2022



Application Summary


Scientific Title of Trial

A cluster randomized, placebo control trial to evaluate the efficacy of a spatial repellent (Mosquito ShieldTM) against Aedes-borne virus infection among children >= 4–16 years of age in the Gampaha District, Sri Lanka


Public Title of Trial

A cluster randomized, placebo control trial to evaluate the efficacy of a spatial repellent (Mosquito ShieldTM) against Aedes-borne virus infection among children >= 4–16 years of age in the Gampaha District, Sri Lanka


Disease or Health Condition(s) Studied

Aedes-borne Virus


Scientific Acronym

None


Public Acronym

AEGIS ABV RCT


Brief title

Spatial Repellents for Vector Control


Universal Trial Number

U1111-1275-3055


Any other number(s) assigned to the trial and issuing authority

P/121/09/2021:FM,UOK: WHO: ERC.0003619 UND IRB: UND # 21-05-6629


Trial Details


What is the research question being addressed?

Does Mosquito ShieldTM reduce the incidence of ABV infection, as measured by DENV specific neutralizing antibodies, in children >=4-16 years of age whose sero-status to dengue at baseline is seronegative, indicating they have never been exposed to dengue, or monotypic, indicating positive antibodies to a single DENV infection?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded : Participants, Investigators, Healthcare providers


Control

Placebo


Assignment

Parallel


Purpose

Prevention


Study Phase

Phase 3


Intervention(s) planned

The study will be conducted in clusters of households, who will be selected from three Medical Officer of Health (MOH) areas in the district of Gampaha: Negombo, Wattala and Kelaniya.

A total of 14,430 total subjects across 3,900 households will be enrolled for monitoring for active disease – labeled the ‘febrile surveillance cohort’. These households will form 30 clusters (15 allocated to intervention, 15 allocated to placebo control), each containing ~187 houses. A subset of this cohort, 3,570 (110-120 per cluster) subjects aged >=4-16 years that test seronegative (naïve) or positive to a previous single dengue virus (DENV) infection (monotypic) at baseline sampling will also be enrolled for measuring DENV infection based on laboratory-confirmed seroconversion – labeled the ‘longitudinal cohort’ All participating houses in each cluster will be monitored entomologically for adult Aedes aegypti surveys for 3 months before deployment of the spatial repellent (SR) intervention and monthly after the intervention is in place. Entomological surveys will include monitoring of indoor Ae. aegypti adult population densities and blood-fed status.

Mapping of the study area and census measurements: Prior to enrollment, all structures in the study area will be mapped using GPS coordinates and assigned a unique Household Identification Number (HIN). SR Intervention: The SR will be a new formulation of transfluthrin. This active ingredient (AI) is widely used in mosquito coils and other household pest control products worldwide. The new formulation is a passive emanator that will release the AI over a period of up to four weeks, Mosquito ShieldTM. The emanator will consist of a pre-treated piece of cellulose acetate or other medium, which will be positioned within consenting households according to manufacturer specifications of 2unit/9m2. A placebo product of matched design with inert ingredients will be applied similarly. Each Mosquito ShieldTM received directly from industry partner(s) will have a Unique Identifier Code (UIC) identifying the contents as having the AI or blank/placebo. Industry partners will ensure that the listing of UICs is accurate and kept strictly confidential. The intervention will be carried out for 24 months. Both SR and placebo interventions will be replaced every 4 weeks throughout the 24 months of follow up with intervention.

The external statistician serving on the Data Safety Monitoring Board (DSMB) will use a random number generator to assign clusters to SR or placebo treatment arm. All households within the intervention arm (randomly chosen) will be assigned active products with all houses within the control arm (randomly chosen) receiving blank/placebo. Both participants and study staff will be blinded as to whether a study cluster is receiving the active SR or placebo product.


Inclusion criteria

LONGITUDINAL SEROCONVERSION Individual Level Inclusion Criteria: >= 4 – 16 years of age Plans to stay in residence and/or study area for a minimum of 24 months Resident of household or frequent visitor (~20% of day hours in house / month)

FEBRILE SURVEILLANCE Household Level Inclusion Criteria: • Adult head of households agrees to census, health visits and logging resident symptoms when febrile (or in the case of suspected Zika in the absence of fever, presenting with rash, arthralgia, arthritis or non-purulent conjunctivitis). • Individuals spend a minimum of 4hrs per week during the daytime hours or sleep in the house.

FEBRILE SURVEILLANCE Individual Level Inclusion Criteria: • >= 6mo of age. • Fever at the time of presentation or report of feverishness within the previous 24 hours or presenting with a rash, arthralgia, arthritis or non-purulent conjunctivitis (suspicion of ZIKA determined by project physician) • Individual who spends a minimum of 4 hours per week within the household or sleeps in the house.

ENTOMOLOGICAL MONITORING Household Level Inclusion Criteria: • Adult head of household agrees to surveys. • Properties where study personnel do not identify a security risk (i.e., site where abusive substances are sold, residents are always drunk or hostile).

SPATIAL REPELLENT INTERVENTION Household Level Inclusion Criteria: • Adult head of households agrees to have intervention applied inside the home and to provide access to team member at 4-week intervals to change products. • Properties where study personnel do not identify a security risk (i.e., site where abusive substances are sold, residents are always drunk or hostile).


Exclusion criteria

LONGITUDINAL SEROCONVERSION Individual Level Exclusion Criteria: • < 4 and > 16 years of age • Plans to leave residence and/or study area within next 24 months • Temporary visitor to household (<20% of day hours in house/ month)

FEBRILE SURVEILLANCE Household Level Exclusion Criteria: • Adult head of households does not agree to census, health visits or logging symptoms of residents. • Households where study personnel identify a security risk (i.e., site where abusive substances are sold, residents are always drunk or hostile). • Sites where no residents spend time during the day (i.e. work 7d a week outside the home).

FEBRILE SURVEILLANCE Individual Level Exclusion Criteria: • < 6mo of age. • No fever at time of presentation or report of feverishness within the previous 24 hours or not reporting with a rash, arthralgia, arthritis or non-purulent conjunctivitis • Individuals who have spent less than 4 hours in the household during the week prior to illness.

ENTOMOLOGICAL MONITORING Household Level Exclusion Criteria: • Adult head of household does not agree to surveys. • Properties where study personnel identify a security risk (i.e., site where abusive substances are sold, residents are always drunk or hostile).

SPATIAL REPELLENT INTERVENTION Household Level Exclusion Criteria: • Adult head of household does not agree to Mosquito ShieldTM deployment or study team access. • Properties where study personnel identify a security risk (i.e., site where abusive substances are sold, residents are always drunk or hostile



Primary outcome(s)

1.

Incidence of Aedes-borne virus (ABV) infection assessed by serologic testing of scheduled longitudinal blood samples

Seroconversion to dengue from baseline (pre-intervention) and follow-up (post-intervention) samples as well as ABV active disease rates will be compared between active intervention and placebo (control) clusters.

The primary endpoint is the fraction of monotypic or seronegative individuals who seroconvert to an arbovirus during the follow-up period post randomization with intervention. Here, the intervention follow-up period is 2 years after initial deployment of SR or placebo.

[

There will be 3 blood samplings from longitudinal cohort participants for measure of seroconversion: one for baseline serostatus characterization (T0), a second at 12 months (T1) and a third at 24 months (T2) from time of initial placement of intervention.

]

Secondary outcome(s)

1.

Clinically apparent laboratory confirmed cases of Aedes-borne virus (ABV) disease. Compare laboratory confirmed Aedes-borne virus infection rates in subjects residing in households with active and placebo product, receiving standard entomological surveillance and control procedures by the Ministry of Health of Sri Lanka, as an indicator for ABV disease.

Clinically apparent is defined as an acute infection that causes overt symptoms (fever, rash, etc.) indicating virus circulation in the blood.

[

For the longitudinal cohort participants, acute and convalescent blood sampling based on time of health facility visit when febrile throughout the intervention period.

For other household members participating in febrile surveillance, case definition measured and reported whenever they visit designated health facilities throughout the intervention period.

]
2.

Adult female Aedes aegypti indoor abundance.

Compare adult female Aedes aegypti indoor abundance in households using Procopak mosquito aspiration with active and placebo product as an indicator for reduced mosquito house entry due to effect of product

[

Indoor mosquito collections in enrolled households once every 28 days during intervention

]
3.

Adult female Aedes aegypti blood fed rate.

Compare adult female Aedes aegypti blood fed rate in households using direct abdominal observation by microscopy from Procopak mosquito aspiration sample with active and placebo product as an indicator for reduced mosquito human contact due to effect of product.

[

Samples from indoor mosquito collections in enrolled households once every 28 days during intervention.

]
4.

Diversion of Aedes aegypti mosquitoes into untreated houses. Compare adult female Aedes aegypti abundance using Procopak mosquito aspiration in untreated households adjacent to treatment clusters (with active product) to untreated households adjacent to placebo clusters as an indicator for mosquito diversion due to effect of product.

[

Indoor mosquito collections in enrolled households once every 28 days during intervention

]
5.

Overall incidence of Aedes-borne virus (ABV) infection. Seroconversion rates of all children enrolled in the trial, independent of order of infection (i.e., including tertiary and quaternary infections).

[

Based on blood samples taken for longitudinal seroconversion and febrile surveillance from time of initial placement of intervention.

]
6.

Adverse Events (AEs) and Serious Adverse Events (SAEs). Measured by solicited and unsolicited reports during the trial period. Mean, minimum and maximum frequency and percentage of AEs and SAEs across clusters among enrolled subjects will be summarized by treatment arm.

[

AEs and SAEs measured and reported for study participants as events occur throughout the trial period.

]
7.

Incidence of Aedes-borne virus (ABV) infection in subjects residing in households within treatment clusters but without SR product. Compare Aedes-borne virus infection rates between subjects residing in households with SR product in treatment clusters and subjects from the same clusters who did not agree to the SR application in their households but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect due to effect of product.

[

There will be 3 blood samplings from longitudinal cohort participants for measure of seroconversion/incidence: one for baseline serostatus characterization (T0), a second at 12 months (T1) and a third at 24 months (T2) from time of initial placement of intervention.

For other household members participating in febrile surveillance, case definition measured and reported whenever they visit designated health facilities throughout the intervention period.

]
8.

Clinically apparent laboratory confirmed cases of Aedes-borne virus (ABV) disease in subjects residing in households within treatment clusters but without SR product. Compare laboratory confirmed Aedes-borne virus infection rates between subjects residing in households with SR product in households in treatment clusters and individuals from the same clusters who did not agree to the SR application in their households but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect due to effect of product.

[

For the longitudinal cohort participants, acute and convalescent blood sampling based on time of health facility visit when febrile throughout the intervention period. For the whole duration of the trial.

For other household members participating in febrile surveillance, case definition measured and reported whenever they visit designated health facilities throughout the intervention period.

]
9.

Adult female Aedes aegypti indoor abundance using Procopak mosquito aspiration in households within treatment clusters but without SR product. Compare adult female Aedes aegypti indoor abundance in households with SR product in treatment clusters and households from the same clusters who did not agree to the SR application but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect to effect of product.

[

Indoor mosquito collections in enrolled households once every 28 days during intervention

]
10.

Adult female Aedes aegypti blood fed rate using Procopak mosquito aspiration in households within treatment clusters but without SR product. Compare adult female Aedes aegypti blood fed rate in households with SR product in treatment clusters and households from the same clusters who did not agree to the SR application but are receiving standard entomological surveillance and control procedures by the local ministry of health, as an indicator of community effect to effect of product.

[

Samples from indoor mosquito collections in enrolled households once every 28 days during intervention.

]
11.
[]

Target number/sample size

14,430 total subjects will be enrolled for febrile surveillance (7,215 per arm) across 3,900 households (1,950 per arm) that will form a total of 30 clusters.


Countries of recruitment

Sri Lanka


Anticipated start date

2022-08-01


Anticipated end date

2024-07-31


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Unitaid – Global Health Campus Chem. du Pommier 40, 1218 Le Grand-Saconnex, Switzerland


Regulatory approvals

Not Applicable



State of Ethics Review Approval


Status

Approved


Date of Approval

2022-01-11


Approval number

P/121/09/2021


Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Institutional Address:Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
Telephone:+94 11 2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr. Korelege Hasitha Aravinda Tissera
Consultant Epidemiologist
Epidemiology Unit, Ministry of Health, Sri Lanka
0094-11-2695112
0094-77-9169108

korelege@yahoo.co.uk

Contact Person for Public Queries

Dr. Korelege Hasitha Aravinda Tissera
Consultant Epidemiologist
Epidemiology Unit, Ministry of Health, Sri Lanka
0094-11-2695112
0094-77-9169108

korelege@yahoo.co.uk


Primary study sponsor/organization

University of Notre Dame

University of Notre Dame, Notre Dame, IN 46556, USA



Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description

N/A


Study protocol available

No


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results