LLIN Evaluation in Uganda Project

Malaria Clinical Trial

— LLINEUP2  

Official title:

Impact of Long-lasting Insecticidal Nets (LLINs) Treated With Pyrethroid Plus Pyriproxyfen vs LLINs Treated With Pyrethroid Plus Piperonyl Butoxide on Malaria Incidence in Uganda: a Cluster-randomised Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04566510
• Other study ID #: LLINEUP2
• Secondary ID: U19AI089674
• Status: Completed
• Phase: N/A
• Start date: October 17, 2020
• Est. completion date: March 31, 2023

Study information

• Verified date: May 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In Uganda, the National Malaria Control Division (NMCD) and implementing partners plan to deliver long-lasting insecticidal nets (LLINs) nationwide in 2020-21, through a mass distribution campaign supported by generous contributions from international donors. LLINs will be distributed free-of-charge to all Ugandan households, aiming to achieve universal coverage. The Against Malaria Foundation has agreed to provide LLINs treated with a pyrethroid insecticide plus pyriproxyfen (PPF) (Royal Guard, Disease Control Technology) and LLINs treated with a pyrethroid insecticide plus piperonyl butoxide (PBO) (PermaNet 3.0, Vestergaard), presenting an opportunity to rigorously evaluate and compare these two LLINs at scale across Uganda. In collaboration with the MOH, the investigators propose to embed a cluster-randomised trial to compare the impact of LLINs with PPF to LLINs with PBO into Uganda's 2020 LLIN distribution campaign. The primary objective of the study is: To evaluate the impact of LLINs treated with a pyrethroid insecticide plus pyriproxyfen (PPF LLINs), as compared to LLINs treated with a pyrethroid plus piperonyl butoxide (PBO LLINs), on malaria incidence in Uganda. The study will test the hypothesis that malaria incidence will be lower in intervention clusters (randomised to receive PPF LLINs) than in control clusters (randomised to receive PBO LLINs).

Description:

This rigorous, cluster-randomised trial will evaluate the impact of long-lasting insecticidal nets (LLINs) distributed in Uganda through the 2020-21 national universal coverage campaign. A cluster has been defined as the catchment area of a Malaria Reference Centre (MRC). A total of 64 clusters have been included in the study, covering 32 high malaria burden districts in Uganda where IRS is not being implemented. Clusters have been randomised in a 1:1 ratio in blocks of two by district to receive one of two types of LLINs: (1) pyriproxyfen (PPF) LLINs (Royal Guard) [n=32] and (2) piperonyl butoxide (PBO) LLINs (PermaNet 3.0) [n=32].

The intervention, including delivery of the LLINs and social and behaviour change communication (SBCC), will be led by the Ugandan National Malaria Control Division (NMCD) and other stakeholders. Currently, LLINs are scheduled to be delivered in the study areas from October 2020 to January 2021. The evaluation will include health facility surveillance at the MRCs to generate continuous estimates of malaria incidence for each MRC catchment area, cross-sectional community surveys at baseline (if additional resources are available), and at 12- and 24-months after LLIN distribution to gather information on net survivorship and use, and parasite prevalence in children 2-10 years of age, entomology surveys, and assessment of net durability and efficacy. The primary outcome of the trial will be malaria incidence as estimated using the health facility surveillance.

For each cluster the study will use a 'fried egg' approach for delivering the intervention ('egg white') and measuring our outcomes ('egg yolk'). The 'white' of the egg will include one sub-county per cluster, where the MRC is located. PPF LLINs and PBO LLINs will be distributed to the designated sub-county, as allocated in the randomisation. The 'yolk' of the egg will be the catchment area directly surrounding each MRC, where care-seeking at the MRC is expected to be high (i.e. if someone within the catchment area develops malaria, they are likely to seek care at the MRC). To determine the population of the MRC catchment areas, and to generate a sampling frame for the community surveys, the investigators will do the following: (1) define the catchment area of each MRC before the onset of the trial using data on village of residence from patients attending the MRCs, (2) map and enumerate all households within the MRC catchment areas before the 12-month community survey, and (3) conduct a census survey within each MRC catchment area to generate an accurate estimate of the study population in which study outcomes will be measured concurrently with the 12-month community survey.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217086
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

A) Primary outcome: All patients who present to the outpatient departments of the MRCs

B) Community surveys for secondary outcomes:

Inclusion Criteria:

• At least one adult aged 18 years or older present

• Adult is a usual resident who slept in the sampled household on the night before the survey

• Agreement of the adult resident to provide informed consent for the household survey

Exclusion Criteria:

• Dwelling destroyed or not found

• Household vacant

• No adult resident home on more than 3 occasions

Related Conditions & MeSH terms

• Malaria

Intervention

Other:
• long lasting insecticidal nets with alpha-cypermethrin + pyriproxyfen (PPF LLIN, Royal Guard))
Next-generation bed net combining insecticides with different modes of action
• long lasting insecticidal nets with deltamethrin + piperonyl butoxide (PBO LLIN, PermaNet 3.0))
Next-generation bed net combining an insecticide with a synergist

Behavioral:
• Social behaviour change communication
SBCC activities will use digital and other platforms, similar to those used for the COVID-19 response, including the following: (1) LLIN launch on television and radio; (2) regional advocacy meetings on Zoom; (3) mass media platforms (for advertisements, mini skits, DJ mentions, radio spots, interactive talks); (4) social media platforms; (5) VHTs; (6) operation hotlines and toll-free call centres; (7) community mobilisation (megaphones); and (8) use of appropriate information, education, and communication materials. Communication will include messages about COVID-19, malaria, and use, care, repair and repurposing of LLINs.

Locations

Country	Name	City	State
Uganda	Infectious Diseases Research Collaboration	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Malaria incidence	Number of cases of laboratory-confirmed malaria diagnosed at the MRC among patients residing in the catchment areas per unit time/the population of the catchment areas	24 months following LLIN distribution
Secondary	Prevalence of parasitaemia	Proportion of blood smears positive for parasites by microscopy in children aged 2-10 years at the time of cross-sectional surveys	12 months following LLIN distribution
Secondary	Prevalence of parasitaemia	Proportion of blood smears positive for parasites by microscopy in children aged 2-10 years at the time of cross-sectional surveys	24 months following LLIN distribution
Secondary	Prevalence of anaemia	Proportion of children aged 2-4 years with haemoglobin < 11 g/dL at the time of cross-sectional surveys	12 months following LLIN distribution
Secondary	Prevalence of anaemia	Proportion of children aged 2-4 years with haemoglobin < 11 g/dL at the time of cross-sectional surveys	24 months following LLIN distribution
Secondary	Proportion of households that owned at least one LLIN	Proportion of households with at least one LLIN at the time of cross-sectional surveys	12 months following LLIN distribution
Secondary	Proportion of households that owned at least one LLIN	Proportion of households with at least one LLIN at the time of cross-sectional surveys	24 months following LLIN distribution
Secondary	Proportion of households that owned at least one LLIN for every two occupants	Proportion of households with at least one LLIN per every two occupants at the time of cross-sectional surveys	12 months following LLIN distribution
Secondary	Proportion of households that owned at least one LLIN for every two occupants	Proportion of households with at least one LLIN per every two occupants at the time of cross-sectional surveys	24 months following LLIN distribution
Secondary	Proportion of household residents who slept under an LLIN the previous night	Proportion of households residents who report sleeping under LLIN the previous night at the time of cross-sectional surveys	12 months following LLIN distribution
Secondary	Proportion of household residents who slept under an LLIN the previous night	Proportion of households residents who report sleeping under LLIN the previous night at the time of cross-sectional surveys	24 months following LLIN distribution
Secondary	Incremental cost-effectiveness ratios	USD per disability-adjusted life year adverted and per malaria case adverted	24 months following LLIN distribution