Children discharged after inpatient care for severe anaemia or severe malaria in sub-Saharan Africa remain at elevated risk of death and hospital readmission. The risk is heightened in malaria-endemic areas where recurrent infections are frequent. Post-discharge malaria chemoprevention (PDMC) has shown large reductions in mortality and readmissions in prior work and is recommended by the World Health Organization. Despite this, there is limited evidence from West Africa on how best to deliver PDMC through existing health systems to achieve high adherence and improved clinical outcomes.
This trial protocol responds to the need to identify pragmatic PDMC delivery approaches that can be implemented at scale in routine health services and tailored to urban and rural settings.
Primary objective:
Secondary objectives:
This is a cluster-randomised implementation trial conducted in central and southern Benin. The study includes both urban and rural settings and is implemented within the catchment areas of two referral hospitals.
Clusters are defined geographically as villages within hospital catchment areas. The trial employs a three-arm parallel design with equal allocation (1:1:1) to the intervention arms.
Villages within the two referral hospital catchment areas serve as clusters. Clusters will be randomly assigned in a 1:1:1 ratio to one of the three study arms. The cluster design is intended to evaluate delivery strategies at the community level and to reduce contamination between different approaches.
Eligible participants are children under 10 years of age who were hospitalised with severe anaemia or severe malaria and are clinically stable at the time of discharge. Caregivers of eligible children are enrolled at discharge and children will be followed for 14 weeks post-discharge.
The source specifies these inclusion criteria; further operational details on exclusion criteria and screening procedures were not reported in the source.
Three PDMC delivery strategies are compared:
Arm A: Facility-based drug distribution — all PDMC courses are dispensed at hospital discharge and adherence support consists of community health worker (CHW) home visit reminders.
Arm B: Community-based monthly delivery — CHWs provide monthly community-based delivery of the PDMC courses combined with phone reminders.
Arm C (control): Full dispensing at discharge without adherence support — all courses are given to caregivers at discharge but no structured adherence support is provided.
The trial will evaluate which of these pragmatic delivery mechanisms leads to the highest completion of the PDMC regimen when implemented through routine health system channels.
All participants are to receive three courses of dihydroartemisinin–piperaquine at weeks 2, 6 and 10 after discharge. Each course comprises multiple doses such that the full PDMC regimen equals three courses or nine doses by the trial definition. Children will be followed for 14 weeks post-discharge to capture adherence and clinical events.
Primary endpoint:
Secondary endpoints include:
The source does not provide additional detail on endpoint adjudication or precise case definitions beyond those listed.
Quantitative outcomes will be analysed using mixed-effects regression models under an intention-to-treat framework, accounting for cluster randomisation. The analysis will compare rates of incomplete adherence and clinical endpoints across the three arms.
Complementary qualitative methods will be used to assess acceptability and feasibility of the delivery strategies among caregivers, providers and policymakers. The source indicates these mixed-methods assessments will inform implementation considerations but does not detail qualitative sample sizes or instruments.
Ethical approval was obtained from the institutional review boards of the Benin Institute of Applied Biomedical Sciences and the Liverpool School of Tropical Medicine. Trial findings will be disseminated to national and international stakeholders through meetings, peer-reviewed publications and major conferences, with specific engagement planned with the World Health Organization and major malaria funding partners to inform PDMC policy and scale-up.
Trial registration numbers provided in the source are ClinicalTrials.gov NCT06601712, registered on 14 September 2024, and Pan African Clinical Trials Registry PACTR202411682724094, registered on 5 November 2024. The source did not report timelines for completion, sample size, or interim monitoring details.