Comparing Chemoprevention Drugs for School-based Malaria Control

Study Overview
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Brief Summary
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This is an individually randomized, controlled, single blind three arm clinical trial of malaria chemoprevention strategies Arm 1: Intermittent preventive treatment with dihydroartemisinin-piperaquine (IPT-DP). Arm 2: Intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) plus chloroquine (CQ) (IPT-SPCQ). Arm 3: Control - students will receive standard of care (no preventive treatment). Outcomes include P. falciparum infection and parasite density, anemia, cognitive function and educational testing, as well as infection prevalence in young children sleeping student's households to assess the impact on transmission.

Detailed Description
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Students attending a single primary school in Machinga District, Malawi who were enrolled in NCT05244954 were offered enrollment in this follow-on study. The intervention will be conducted every 6-weeks during the two school terms which coincide with peak malaria transmission. Students in the IPT-DP arm will be treated with with dihydroartemisinin-piperaquine (DP) (females less than 10 years old and all males) or chloroquine (females 10 years old or older. Students in the IPT-SPCQ arm will be treated with sulfadoxine-pyrimethamine plus chloroquine (females less than 10 years old and all males) or chloroquine alone (females 10 years old or older).

Official Title
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Clinical Trial to Evaluate Intermittent Screening and Treatment and Intermittent Preventive Treatment of Malaria in Asymptomatic Schoolchildren to Decrease P. Falciparum Infection and Transmission: Phase 2 Comparing Drug Regimens

Conditions
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Malaria,Falciparum, Anemia in Children

Intervention / Treatment
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* Drug: Dihydroartemisinin-Piperaquine
* Drug: Chloroquine
* Drug: Sulfadoxine pyrimethamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Students (enrolled in the primary intervention) Previously enrolled in NCT05244954 Currently enrolled in the study school Plan to attend the study school for the remainder of the school year Parent/guardian available to provide written informed consent Younger children in participant households (enrolled in the Household Prevalence survey) Slept in the household for most nights in the last month Age 6-59 months Parent/guardian available to provide written informed consent Exclusion Criteria: Students (enrolled in the primary intervention) Current evidence of severe malaria or danger signs Known adverse reaction to the study drugs History of cardiac problems or fainting Taking medications known to prolong QT Family history of prolonged QT Taking trimethoprim-sulfamethoxazole aka Bactrim or Cotrimoxazole Epilepsy Psoriasis Household members (enrolled in the Household Prevalence survey) Household with more than one school-age child enrolled in the study Current evidence of severe malaria or danger signs

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Students were randomized to three arms in the original trial. In this follow-on study, students will remain in their study arms. Arm 1 which previously received intermittent screening-and-treatment will now receive intermittent preventive treatment with sulfadoxine-pyrimethamine plus chloroquine. Arm 2 which received intermittent preventive treatment with dihydroartemisinin-piperaquine will again receive intermittent preventive treatment with dihydroartemisinin-piperaquine. Arm 3 the control arm will continue as a control. Females 10 years and older (potentially post-menarche) in Arms 1 and 2 will receive chloroquine alone.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent Preventive Treatment with dihydroartemisinin-piperaquine (IPT-DP)<br>All students are treated at each intervention. Treatment will be with DP (females less than 10 years old and all males) or chloroquine (females 10 years old or older). | Drug: Dihydroartemisinin-Piperaquine<br>* Treatment will be with DP (females less than 10 years old and all males) or chloroquine alone (females 10 years old or older).<br>* Other names: Ridmal;Drug: Chloroquine<br>* Treatment of females 10 years old and older in Arm 1 and treatment of all participants in Arm 2.<br>* Other names: Lariago;|
| Experimental: Intermittent Preventive Treatment with sulfadoxine-pyrimethamine plus chloroquine (IPT-SPCQ)<br>All students are treated at each intervention. Treatment will be with SP + CQ (females less than 10 years old and all males) or chloroquine (females 10 years old or older). | Drug: Chloroquine<br>* Treatment of females 10 years old and older in Arm 1 and treatment of all participants in Arm 2.<br>* Other names: Lariago;Drug: Sulfadoxine pyrimethamine<br>* Treatment will be with SP and chloroquine (females less than 10 years old and all males) or chloroquine alone (females 10 years old or older).<br>* Other names: SP;|
| No Intervention: Control<br>Students will not receive preventive treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with P. falciparum infection | detected by polymerase chain reaction (PCR, binary) | 6-8 weeks after the last intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with anemia | World Health Organization age-sex definitions (binary) | 6-8 weeks after the last intervention | 
| Mean hemoglobin concentration | g/dL (continuous) | 6-8 weeks after the last intervention | 
| Total parasite density | log transformed (continuous) | 6-8 weeks after the last intervention | 
| Rate of clinical malaria | cumulative incidence | through study completions, approximately 6 months | 
| P. falciparum prevalence among children less than 5 years old living in households with study participants | detected by PCR | 6-8 weeks after the last intervention | 
| sustained attention | code transmission test score (continuous) | 6-8 weeks after the last intervention | 
| selective attention | selective attention test score (continuous) | 6-8 weeks after the last intervention | 
| Literacy skills | onetest reading test score (continuous) | 6-8 weeks after the last intervention | 
| Math skills | onetest math score (continuous) | 6-8 weeks after the last intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, school, chemoprevention, preventive treatment, education, cognitive function, adolescent, hemoglobin