Intermittent Preventive Treatment of Malaria in School-age Children to Decrease Community Transmission (CRITICal)

Cluster Randomized Trial of Intermittent Preventive Treatment of Malaria in School-age Children to Improve the Health of Students and Decrease Community Transmission

The CRITICal study aims to estimate the effectiveness of intermittent preventive treatment in school children (IPTsc) with dihydroartemisinin-piperaquine (DP) for reducing community level malaria burden. Given that school-aged children are the primary drivers of transmission, the study hypothesis is that IPTsc will reduce this infectious reservoir and thus the burden of malaria in persons of all ages in surrounding communities.

Study Overview

• Status: Not yet recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: dihydroartemisinin-piperaquine

Detailed Description

The CRITICal study is an open label, phase IV, cluster-randomized trial to evaluate the effectiveness of IPTsc with DP administered approximately every 2 months to children attending primary school. Clusters are geographically defined target areas surrounding government-run health facilities previously established and referred to as Malaria Reference Centers (MRCs). A total of 24 clusters (MRCs) will be included in the study. These clusters were selected based on participation in an on-going sentinel site malaria surveillance network in areas with moderate-high malaria transmission intensity. Clusters will be randomized in a 1:1 ratio such that all primary schools serving the populations of each target area will either receive IPTsc or not receive IPTsc. The intervention will be delivered for 2 years and evaluations will continue for 1 additional year after the intervention is stopped. The primary outcome of the study will be malaria incidence within the population of the target areas. Secondary outcomes will include the the prevalence of parasitemia and molecular markers of DP resistance at the community level; the prevalence of parasitemia, anemia, and school attendance among children attending primary school; and estimates of the cost-effectiveness of IPTsc.

• Study Type: Interventional
• Enrollment (Estimated): 4800
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Grant Dorsey, MD, PhD; Phone Number: 415-310-0525; Email: grant.dorsey@ucsf.edu
• Study Contact Backup: Name: Tamara Clark, MHS; Phone Number: 415-517-3444; Email: tamara.clark@ucsf.edu

Study Locations

• Uganda
  • Kampala, Uganda
    • Infectious Diseases Research Collaboration
    • Contact: Joaniter Nankabirwa, MBChB, MSc, PhD; Email: jnankabirwa@yahoo.co.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Child currently attending the participating school.
• Agreement of parent/guardian to provide informed consent.
• Agreement of children aged 8-17 years to provide assent.

Exclusion Criteria:

• Missing school on three consecutive days of the school survey.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IPTsc; DP will be administered approximately every 2 months for two years to all eligible children enrolled in primary schools serving the target areas from clusters randomized to the interventional arm.	Drug: dihydroartemisinin-piperaquine; D-Artepp, is manufactured by Guilin Pharmaceutical Co Ltd, and is prequalified by the WHO and approved for use in Uganda by the National Drug Authority. Standard treatment doses of DP (once a day x 3 days) will be administered using weight-based guidelines targeting a total dose of 6.4 mg/kg dihydroartemisinin and 51.2 mg/kg of piperaquine as per manufacturer's instructions.; Other Names: D-Artepp
No Intervention: No IPTsc; No IPTsc (standard of care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of cases of laboratory-confirmed malaria diagnosed among patients residing in the target area during the period the intervention is implemented	malaria incidence: the number of cases of laboratory-confirmed malaria diagnosed at the MRC among patients residing in the target area, per unit time, divided by the total population of the target area in patients of all ages over the 24-month intervention period	24 months after intervention implemented

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of cases of laboratory-confirmed malaria diagnosed among patients residing in the target area after the intervention is competed	malaria incidence: the number of cases of laboratory-confirmed malaria diagnosed at the MRC among patients residing in the target area, per unit time, divided by the total population of the target area in patients of all ages 12 months after intervention is completed	12 months after intervention is completed
Parasite prevalence among community residents 12 months after the intervention is implemented	Proportion of blood smears positive for parasites by microscopy at the time of community cross-sectional surveys	12 months after the intervention is implemented
Parasite prevalence among community residents 24 months after the intervention is implemented	Proportion of blood smears positive for parasites by microscopy at the time of community cross-sectional surveys	24 months after the intervention is implemented
Parasite prevalence among community residents 12 months after the intervention is completed	Proportion of blood smears positive for parasites by microscopy at the time of community cross-sectional surveys	12 months after the intervention is completed
Prevalence of molecular markers of DP resistance from parasite positive samples from community surveys 12 months after the intervention is implemented	Proportion of parasite positive samples with molecular markers of DP resistance detected	12 months after the intervention is implemented
Prevalence of molecular markers of DP resistance from parasite positive samples from community surveys 24 months after the intervention is implemented	Proportion of parasite positive samples with molecular markers of DP resistance detected	24 months after the intervention is implemented
Prevalence of molecular markers of DP resistance from parasite positive samples from community surveys 12 months after the intervention is completed	Proportion of parasite positive samples with molecular markers of DP resistance detected	12 months after the intervention is completed
Parasite prevalence among schoolchildren 12 months after the intervention is implemented	Proportion of blood smears positive for parasites by microscopy at the time of school surveys	12 months after the intervention is implemented
Parasite prevalence among schoolchildren 24 months after the intervention is implemented	Proportion of blood smears positive for parasites by microscopy at the time of school surveys	24 months after the intervention is implemented
Parasite prevalence among schoolchildren 12 months after the intervention is completed	Proportion of blood smears positive for parasites by microscopy at the time of school surveys	12 months after the intervention is completed
Anemia prevalence among schoolchildren 12 months after the intervention is implemented	Proportion of children with anemia at the time of school surveys Anemia defined based on WHO criteria as: hemoglobin less than 11.5g/dl in children 5 - 11 years of age;; hemoglobin less than 12.0g/dl in children 12 - 14 years of age and non-pregnant girls 15 years and above; and; hemoglobin less than 13.0g/dl in boys 15 years and above) 12 and 24 months after the intervention is implemented and school attendance (defined as the number of days attending school / number of days school in session) over the 24-month intervention period	12 months after the intervention is implemented
Anemia prevalence among schoolchildren 24 months after the intervention is implemented	Proportion of children with anemia at the time of school surveys Anemia defined based on WHO criteria as: hemoglobin less than 11.5g/dl in children 5 - 11 years of age;; hemoglobin less than 12.0g/dl in children 12 - 14 years of age and non-pregnant girls 15 years and above; and; hemoglobin less than 13.0g/dl in boys 15 years and above) 12 and 24 months after the intervention is implemented and school attendance (defined as the number of days attending school / number of days school in session) over the 24-month intervention period	24 months after the intervention is implemented
Anemia prevalence among schoolchildren 12 months after the intervention is completed	Proportion of children with anemia at the time of school surveys Anemia defined based on WHO criteria as: hemoglobin less than 11.5g/dl in children 5 - 11 years of age;; hemoglobin less than 12.0g/dl in children 12 - 14 years of age and non-pregnant girls 15 years and above; and; hemoglobin less than 13.0g/dl in boys 15 years and above) 12 and 24 months after the intervention is implemented and school attendance (defined as the number of days attending school / number of days school in session) over the 24-month intervention period	12 months after the intervention is completed

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Ministry of Health, Uganda; Infectious Diseases Research Collaboration, Uganda
• Investigators: Principal Investigator: Grant Dorsey, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: dihydroartemisinin-piperaquine; intermittent preventive treatment; school children
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria
• Other Study ID Numbers: CRITICAL; U01AI186861 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No