Preventing Malaria in School Children to Protect the Whole Community in Rural Blantyre District, Malawi

This is an individually randomized, controlled, single blind four 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: Intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) (IPT-SPAQ).Arm 4: 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 and disease incidence in young children sleeping student's households to assess the impact on transmission.

Study Overview

• Status: Not yet recruiting
• Conditions: Malaria,Falciparum; Anemia in Children
• Intervention / Treatment: Drug: Dihydroartemisinin-Piperaquine; Drug: Chloroquine; Drug: Sulfadoxine pyrimethamine; Drug: Sulfadoxine-pyrimethamine-amodiaquine

Detailed Description

Students attending primary school in rural Blantyre District, Malawi will be offered enrollment in this 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 13 years old and all males) or chloroquine (females 13 years old or older). Students in the IPT-SPCQ arm will be treated with sulfadoxine-pyrimethamine plus chloroquine (females less than 13 years old and all males) or chloroquine alone (females 13 years old or older). Students in the IPT-SPAQ arm will be treated with sulfadoxine-pyrimethamine plus amodiaquine (females less than 13 years old and all males) or chloroquine alone (females 13 years old or older). Students in the all arms will receive routine malaria education.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lauren M Cohee, MD MS; Phone Number: 00441513517674; Email: lauren.cohee@lstmed.ac.uk
• Study Contact Backup: Name: Ruth van Zalinge; Phone Number: 00441517029396; Email: lstmgov@lastmed.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Student Inclusion Criteria:

• 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

Student Exclusion Criteria:

• 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
• History of epilepsy or psoriasis
• Taking cotrimoxazole for long-term prophylaxis

Younger child Inclusion Criteria

• Slept in the household for most nights in the last month
• Age 6-59 months
• Parent/guardian available to provide written informed consent

Younger child Exclusion Criteria

- Current evidence of severe malaria or danger signs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Students will not receive preventive treatment.
Experimental: Intermittent Preventive Treatment with dihydroartemisinin-piperaquine (IPT-DP); All students are treated at each intervention. Treatment will be with DP (females less than 13 years old and all males) or chloroquine (females 13 years old or older).	Drug: Dihydroartemisinin-Piperaquine; Treatment will be with DP (females less than 13 years old and all males) or chloroquine alone (females 13 years old or older).; Other Names: Eurartesim; Artekin; Ridmal; DP; DuoCotecxin; D-Artepp; Drug: Chloroquine; Treatment will be with CQ alone if female and 13 years old or older in all study arms. Treatment in combination with SP in Arm 2 (females less than 13 years old and all males).; Other Names: Aralen; Hydroxychloroquine; Lariago
Experimental: Intermittent Preventive Treatment with sulfadoxine-pyrimethamine plus chloroquine (IPT-SPCQ); All students are treated at each intervention. Treatment will be with SP and CQ (females less than 13 years old and all males) or chloroquine (females 13 years old or older).	Drug: Chloroquine; Treatment will be with CQ alone if female and 13 years old or older in all study arms. Treatment in combination with SP in Arm 2 (females less than 13 years old and all males).; Other Names: Aralen; Hydroxychloroquine; Lariago; Drug: Sulfadoxine pyrimethamine; Treatment in combination with CQ in Arm 2 (females less than 13 years old and all males). Treatment in combination with AQ in Arm 3 (females less than 13 years old and all males).; Other Names: SP
Experimental: Intermittent Preventive Treatment with sulfadoxine-pyrimethamine plus amodiaquine (IPT-SPAQ); All students are treated at each intervention. Treatment will be with SP and AQ (females less than 13 years old and all males) or chloroquine (females 13 years old or older).	Drug: Chloroquine; Treatment will be with CQ alone if female and 13 years old or older in all study arms. Treatment in combination with SP in Arm 2 (females less than 13 years old and all males).; Other Names: Aralen; Hydroxychloroquine; Lariago; Drug: Sulfadoxine-pyrimethamine-amodiaquine; Treatment in Arm 3 (females less than 13 years old and all males).; Other Names: SPAQ; SPAQ-Co

What is the study measuring?

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
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
Number of participants with anemia	World Health Organization age-sex definitions (binary)	6-8 weeks after the last intervention
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
Rate of clinical malaria	cumulative incidence	through study completion (approximately 6 months), and 6 months following the intervention
Literacy skills	Early grade reading assessment	6-8 weeks after the last intervention
Math skills	Early grade math assessment	6-8 weeks after the last intervention
Rate of clinical malaria among children less than 5 years old living in households with study participants	cumulative incidence	through study completion (approximately 6 months)

Collaborators and Investigators

• Sponsor: Liverpool School of Tropical Medicine
• Collaborators: Kamuzu University of Health Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 9, 2023
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Chloroquine; Pyrimethamine; Hydroxychloroquine; Piperaquine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine; Artenimol
• Other Study ID Numbers: 23-048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data that underlie results in a publication
• IPD Sharing Time Frame: After publication
• IPD Sharing Access Criteria: Public access with registration to allow tracking
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No