Clinical trial NCT06155448: Perennial Malaria Chemoprevention (PMC) Effect Study
Official title: Perennial Malaria Chemoprevention (PMC) Effect Study: Nigeria Operational Feasibility and Effectiveness
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Malaria
Keywords: PMC
Chemoprevention
Malaria
Integrated delivery
Lead sponsor: Malaria Consortium
Sponsor class: OTHER
Collaborators: name: Nigerian Institute of Medical Research
name: London School of Hygiene and Tropical Medicine
name: Northwestern University
First posted: 2023-12-04
Enrollment: 2000
Sex: ALL
Minimum age (years): 10
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention arm will comprise PMC-plus: A 6-scheduled dose regimen administered to eligible children at 10 weeks, 14 weeks, 6 months, 9 months, 12 months and 15 months of age concurrently with EPI vaccinations DTP2/Penta2, DTP3/Penta3, vitamin A, and measles immunisation where appropriate. Eligible children attending the participating health facilities for other reasons beyond EPI would be invited to receive additional monthly doses between scheduled EPI-linked visits up until the child reaches 18 months of age
Primary purpose: PREVENTION

Brief summary: The Malaria Consortium Nigeria (MC) will coordinate a trial of PMC in Osun State, Nigeria with strategic support from the National Malaria Elimination Programme of the Government of Nigeria (NMEP) and financial support from the BMGF. The primary purpose of the study is to provide evidence of the impact of PMC on malaria burden and related clinical outcomes, and its operational feasibility for policy decision and the inclusion of PMC into upcoming programme and funding cycles for its National Malaria Control Strategic Plan. The objectives are:

1. To evaluate the impact of PMC in children aged 2-18 months on key child health outcomes including malaria burden, hospitalisations, and anaemia.
2. To describe indicators of operational feasibility of PMC by identification and measurement of key determinants of successful uptake and implementation of PMC.

Detailed description: Study Design and Procedures The impact of PMC will be evaluated in a two-arm cluster-randomised controlled trial and nested case control study. The primary impact outcomes are a comparison of the incidence of clinical malaria in children 2-18 months of age visiting selected sentinel primary care facilities in intervention arm and comparison (standard care) arm wards in the study site, and the protective effectiveness of SP in the 28 days following a dose in intervention arm wards. A ward, the lowest level of health services administration for the State, will be the cluster unit of randomisation. A single facility meeting study eligibility criteria will be selected in each ward as the sentinel facility in which study outcomes will be evaluated (bi-monthly extraction of data on confirmed malaria cases by the study team). Strengthened age recording (full age in months) of visiting children will be implemented in each sentinel facility. An identical programme of data collection will take place in secondary and tertiary hospitals which serve the study site and will include data on admissions of children with an address in a study ward.

Cross sectional household 'malariometric' surveys will be conducted in catchment area communities of ;in both arms at baseline, at 18 months following start of PMC implementation, and at 24 months once implementation ends. Data on coverage of PMC doses (main indicator of feasibility) will be collected from child health record cards or caregiver report for children in the age groups eligible to receive the doses in question. Additional data on malaria infection (RDT test) and anaemia prevalence will be collected during the cross sectional surveys.

Collection of malaria data from sentinel facilities for children aged 19 months and older who were eligible to receive PMC during the implementation period (but too old at the end of implementation) will continue for an additional 12 months following the end of implementation period. The potential rebound effects of the intervention will be assessed in this period by a comparison of incidence rates in control and intervention arm wards.

Sample size (impact): The expected reduction in incidence of malaria in children aged 2-18 months after 18 months of implementation is conservatively estimated to be between 18%-32% contingent on the level of coverage of PMC doses in the intervention arm; enrolling 40 wards in each arm (for a total of 80) will provide 90% power to detect an impact of 20% in this age group after 18 months of implementation, and 95% after 24 months of implementation. We will also recruit children aged 2-18m with clinical malaria from 8 of the 40 intervention arm sentinel facilities and match these to 2-4 controls to have 95% power to detect a protective effectiveness of 50% reduction in malaria in the 28 days following a dose of SP.

Sample size (feasibility): To estimate coverage for any dose of 50% with a margin of error of 8%, assuming a design effect of 2.44 based on an implied intra cluster correlation coefficient of 0.18 (Nigeria DHS) to account for the cluster sample strategy, and allowing for 10% non-response, 25 children aged 2-36 months will be required in each cluster (ward), for a total of 25x40=1,000 in each arm of the study and with a total of 2000 across both arms.

Follow-up period: The total follow-up period of implementation will be 24 months, starting April 2023 to March 2025. The primary evaluation of impact and feasibility will occur in the first 18 months of implementation (April 2023 - September 2024).

Description of intervention: Health facility staff will be trained to offer scheduled doses of SP linked to the EPI delivery platform in children aged 10 weeks to 15 months (six doses), plus additional 'pragmatic' monthly doses offered outside of the EPI schedule to children up to 18 months of age (up to eleven additional doses). Additional social mobilisation and social behaviour change (SBC) activities will be conducted throughout the implementation period to increase demand and uptake of vaccination and PMC services in the study population.

Pharmacovigilance: Spontaneous (passive) adverse event (AE) reporting will be implemented in all study facilities (both sentinel and non-sentinel facilities in study wards),and will include training of health facility staff to recognise and manage known potential side effects of SP, and the development of picture based AE cards and posters for families and facility staff. Children with severe AEs will be referred to secondary/tertiary facilities as appropriate. A programme of active AE monitoring in a cohort of children will be additionally implemented in 2 facilities in each intervention arm in order to collect more detailed data on timings and symptoms following PMC or EPI doses, and to compare AE reporting rates between arms.

Additional activities: Cross-sectional health facility surveys and stakeholder interviews will take place during the follow-up period to collect data on implementation outcomes, alongside qualitative data collection in focus group discussions and in-depth interviews.

Eligibility criteria: Inclusion Criteria:

* Aged 10 weeks to 24 months
* Healthy

Exclusion Criteria:

* severe acute malnutrition, or
* allergic to sulphur containing medication,
* HIV positive,
* taking cotrimoxazole as prophylaxis or treatment, or SP, or other sulphur-containing medication in the previous 4 weeks, and
* children with a positive malaria RDT

Primary outcomes:
measure: . Incidence rate of clinical malaria
timeFrame: 18 months
measure: Protective effectiveness of SP
timeFrame: 18 months
Secondary outcomes:
measure: Prevalence of malaria infection
timeFrame: 18 months
measure: Prevalence of anaemia
timeFrame: 18 months
measure: Incidence rate of all-cause hospitalisations
timeFrame: 18 months
measure: Incidence rate of clinical malaria (rebound period)
timeFrame: 12 months following implementation
measure: Coverage of scheduled SP doses
timeFrame: 18 months
measure: Coverage of vaccine or vitamin A doses
timeFrame: 18 months of implementation
measure: Acceptability of PMC
timeFrame: 18 month
measure: Integration of PMC into EPI delivery platform
timeFrame: 18 months
measure: Appropriateness of PMC
timeFrame: 18 months
measure: Fidelity of PMC delivery
timeFrame: 18months
measure: . Adoption of PMC by facilities
timeFrame: 18 months
Other outcomes:
Locations:
city: Oshogbo
country: Nigeria
facility: Ministry of Health
state: Osun
Study officials:
affiliation: Malaria Consortium
name: James Tibenderana, PhD
role: PRINCIPAL_INVESTIGATOR
References: