Safety and Effectiveness of Artemisinin-based Combination Therapies (ACTs) With Repeated Treatments for Uncomplicated Falciparum Malaria Over a Three-year Period

Study Overview
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Brief Summary
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A community-based, open-label, cluster-randomised longitudinal study in which children are randomized according to village health worker catchment areas comparing the safety and effectiveness of repeated treatments with artemether-lumefantrine (AL) over a 3-year period in children 4-48 months to that of repeated treatment with dihydroartemisinin-piperaquine (DHA-PPQ).

Official Title
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Programmatic Implementation of ACTs in Malawi: Safety and Effectiveness of Combination Therapies With Repeated Treatments for Uncomplicated P. Falciparum Malaria Over a Three-year Period

Conditions
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Malaria

Intervention / Treatment
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* Drug: Artemether-lumefantrine combination


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Aged between 4 months and 11 months at the time of randomization Bodyweight ≥ 5 kg at the time of randomization Provision of informed consent by parent or guardian Intention to stay in the study area for the time of the study Exclusion criteria Ongoing participation into another clinical study involving ongoing or scheduled treatment with medicinal products Intent to reside outside of catchment area during the course of the study Known hypersensitivity to the study drug randomized to Known pre-existing hearing problem or neurological impairment Known need at the time of randomization for concomitant prohibited medication Suspected non-compliance with the follow-up schedule

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 48 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artemether-lumefantrine<br>Children in this study arm will be treated with artemether-lumefantrine during a three year follow-up period each time a child develops uncomplicated malaria. | Drug: Artemether-lumefantrine combination<br> <br> |
| Active Comparator: Dihydroartemisinin-piperaquine<br>Children in this study arm will be treated with dihydroartemisinin-piperaquine during a three year follow-up period each time a child develops uncomplicated malaria. | Drug: Artemether-lumefantrine combination<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of ototoxicity at 18 months and 36 months of enrolment. |  | At 18 mo and 36 month of follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical malaria during 18 months and 36 months of follow-up |  | 18 and 36 months of follow up |