Intermittent Preventive Treatment of Malaria in Schoolchildren

Study Overview
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Brief Summary
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This will be a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety and tolerability of antimalarial regimens in healthy schoolchildren. The primary objective of the study is to compare the efficacy of different combination antimalarial regimens, including amodiaquine + sulfadoxine-pyrimethamine (AQ+SP), dihydroartemisinin-piperaquine (DP), and placebo, to SP for intermittent preventive treatment (IPT) in schoolchildren, as measured by risk of parasitaemia (unadjusted by genotyping) after 42 days of follow-up. This will assess both the efficacy for treatment of asymptomatic infections and the efficacy for prevention of new infections.

Detailed Description
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The study will be carried out among children aged ≥ 8 to < 14 years (boys) and ≥ 8 to < 12 years (girls) attending primary schools in Tororo district. Schools will be selected using convenience sampling with the assistance of the district and the education sector. The target population includes children attending primary schools in Uganda. The accessible population includes the children attending the participating primary schools in classes 3-7 in Tororo district. Children who meet the selection criteria for participation in the study will be randomized to treatment with one of the four study regimens and will be followed for 42 days. Repeat evaluations will be performed on days 1, 2, 3, 7, 14, 28, and 42 (and any unscheduled day that a student is ill) and will include assessment for the occurrence of adverse events. Treatment efficacy outcomes will be assessed using revised WHO outcome classification criteria. Acceptability of treatment regimens will be assessed using a questionnaire administered to participating students on day 7. The primary outcome measure is risk of parasitaemia (unadjusted by genotyping) after 42 days of follow-up.

Official Title
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IPT in Schoolchildren: Comparison of the Efficacy, Safety, and Tolerability of Antimalarial Regimens in Uganda

Conditions
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Malaria, Intermittent Preventive Treatment

Intervention / Treatment
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* Drug: sulfadoxine-pyrimethamine
* Drug: amodiaquine + sulfadoxine-pyrimethamine
* Drug: dihydroartemisinin-piperaquine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 8 to < 14 years (boys), ≥ 8 to < 12 years (girls) Student enrolled at participating school in classes 3-7 Provision of informed consent from parent or guardian Provision of assent by student Exclusion Criteria: Known allergy or history of adverse reaction to study medications Onset of menstruation (girls) Fever (≥ 37.5°C axillary) or history of fever in the previous 24 hours Evidence of severe malaria or danger signs Haemoglobin < 7.0 gm/dL Parasite density > 10,000/ul

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 13 Years

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Combination of Amodiaquine +sulfadoxine-pyrimethamine<br>Combination of Amodiaquine (Camoquin, Parke-Davis, 200 mg tablets, 10 mg/kg on days 0 and 1, and 5 mg/kg on day 2) + sulfadoxine-pyrimethamine (Fansidar, Roche, 500 mg/25 mg tablets, 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine per treatment as a single dose) given as oral tablets | Drug: amodiaquine + sulfadoxine-pyrimethamine<br>* Amodiaquine: 10 mg/kg po daily for 3 days (on days 0, 1, 2) SP: 25 mg/kg po once on day 0<br>* Other names: Fansidar, Roche;|
| Active Comparator: Dihydroartemisinin-piperaquine<br>Dihydroartemisinin-piperaquine (Duocotexin, Holley Pharm, 40 mg dihydroartemisinin/320 mg piperaquine tablets targeting a total dose of 6.4 and 51.2 mg/kg of dihydroartemisinin and piperaquine, respectively, given in 3 equally divided daily doses to the nearest ¼ tablet) | Drug: dihydroartemisinin-piperaquine<br>* 2.1/17.1 mg/kg daily for three days (on days 0, 1, 2)<br>* Other names: Duocotexcin, Holley Cotec Pharmaceuticals;|
| Placebo Comparator: Placebo<br>Placebo (had no active ingredients, produced by Cosmos Limited, Nairobi, Kenya) | Other: Placebo<br>* dosed as for amodiaquine (10mg/kg po daily on days 1, 2)<br>* Other names: No active ingredient;|
| Active Comparator: Sulfadoxine-pyrimethamine alone<br>sulfadoxine-pyrimethamine (Fansidar, Roche, 500 mg/25 mg tablets, 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine per treatment as a single dose) given as oral tablets | Drug: sulfadoxine-pyrimethamine<br>* 25 mg/kg po once on day 0<br>* Other names: Fansidar, Roche;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of parasitaemia (unadjusted by genotyping) | Proportion of thick blood smears that are positive for asexual parasites | after 42 days of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of recrudescence (adjusted by genotyping) in children who were parasitaemic at enrollment | Proportion of thick blood smears that are positive with the same asexual parasites at baseline and on the day of failure at genotyping | after 42 days of follow-up | 
| Risk of new infection (adjusted by genotyping) in all children | Proportion of thick blood smears that are positive for new asexual parasites on day of failure at genotyping | after 42 days of follow-up | 
| Risk of clinical failure due to recrudescence (adjusted by genotyping) in children who were parasitaemic at enrollment | Proportion of children that have fever and a positive thick blood smear for asexual parasites on the day of failure | after 42 days of follow-up | 
| Risk of parasitological failure due to recrudescence (adjusted by genotyping) in children who were parasitaemic at enrollment | Proportion of children with a thick blood smear that is positive for asexual parasites but have no fever on the day of failure | after 42 days of follow-up | 
| Mean haemoglobin | Average hemoglobin concentration | at day 42 | 
| Mean change in haemoglobin | The mean change in hemoglobin measures | between day 0 to day 42 | 
| Risk of serious adverse events | Any untoward medical occurrence in a participant taking study medication after 14 and 42 days of follow up leading to death, disability, hospitalization or extended hospitalization | over 42 days of follow-up | 
| Risk of all adverse events | Any untoward medical occurrence in a participant taking study medication after 14 and 42 days of follow up | after 14 and 42 days of follow-up | 
| Acceptability of IPT regimens | Perceived willingness to take study medication as routine preventive treatment | on day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Intermittent preventive treatment, Efficacy, Safety, Tolerability, Schoolchildren, Uganda