Clinical trial NCT04566510: LLIN Evaluation in Uganda Project
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Keywords: long-lasting insecticidal net
pyriproxyfen
piperonyl butoxide
alpha-cypermethrin
deltamethrin
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2020-09-28
Enrollment: 32895
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: cluster-randomised trial
Primary purpose: PREVENTION

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Malaria Incidence
timeFrame: 24 months following LLIN distribution
Secondary outcomes:
measure: Prevalence of Parasitaemia
timeFrame: 12 months following LLIN distribution
measure: Prevalence of Parasitaemia
timeFrame: 24 months following LLIN distribution
measure: Prevalence of Anaemia
timeFrame: 12 months following LLIN distribution
measure: Prevalence of Anaemia
timeFrame: 24 months following LLIN distribution
measure: Proportion of Households That Owned at Least One LLIN
timeFrame: 12 months following LLIN distribution
measure: Proportion of Households That Owned at Least One LLIN
timeFrame: 24 months following LLIN distribution
measure: Proportion of Households That Owned at Least One LLIN for Every Two Occupants
timeFrame: 12 months following LLIN distribution
measure: Proportion of Households That Owned at Least One LLIN for Every Two Occupants
timeFrame: 24 months following LLIN distribution
measure: Proportion of Household Residents Who Slept Under an LLIN the Previous Night
timeFrame: 12 months following LLIN distribution
measure: Proportion of Household Residents Who Slept Under an LLIN the Previous Night
timeFrame: 24 months following LLIN distribution
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Infectious Diseases Research Collaboration
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Sarah Staedke, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Infectious Diseases Research Collaboration
name: Moses Kamya, MBChB, MMed, PhD
role: PRINCIPAL_INVESTIGATOR
References: