Intermittent Preventive Treatment of Malaria in Schoolchildren

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

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.

Study Overview

• Status: Completed
• Conditions: Malaria; Intermittent Preventive Treatment
• Intervention / Treatment: Drug: amodiaquine + sulfadoxine-pyrimethamine; Drug: dihydroartemisinin-piperaquine; Other: Placebo; Drug: sulfadoxine-pyrimethamine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 780
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Combination of Amodiaquine +sulfadoxine-pyrimethamine; 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; Amodiaquine: 10 mg/kg po daily for 3 days (on days 0, 1, 2) SP: 25 mg/kg po once on day 0; Other Names: Fansidar, Roche; Camoquin, Pfizer
Active Comparator: Dihydroartemisinin-piperaquine; 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; 2.1/17.1 mg/kg daily for three days (on days 0, 1, 2); Other Names: Duocotexcin, Holley Cotec Pharmaceuticals
Placebo Comparator: Placebo; Placebo (had no active ingredients, produced by Cosmos Limited, Nairobi, Kenya)	Other: Placebo; dosed as for amodiaquine (10mg/kg po daily on days 1, 2); Other Names: No active ingredient
Active Comparator: Sulfadoxine-pyrimethamine alone; 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; 25 mg/kg po once on day 0; Other Names: Fansidar, Roche

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of Parasitaemia (Unadjusted by Genotyping)	Proportion of participants whose 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 Participants Who Were Parasitaemic at Enrollment	Proportion of participants whose 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 Participants	Proportion of participants whose 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 who were parasitaemia at enrollment, with subsequent fever and a positive thick blood smear for asexual parasites on the day of failure during follow-up	Over 42 days of follow-up
Mean Change in Haemoglobin	Haemoglobin measured in g/dL; Mean change in haemoglobin calculated as the difference in mean haemoglobin (g/dL) on Day 42 - Day 0, in children treated with the different antimalarial regimens	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
Acceptability of IPT Regimens	Perceived willingness to take study medication as routine preventive treatment	on day 7
Risk of Clinical Failure Due to Recrudescence (Adjusted by Genotyping) in Children Who Were Parasitaemic at Enrollment	Proportion of children who were parasitaemia at enrollment, with subsequent fever and a positive thick blood smear for asexual parasites on the day of failure during follow-up	after 42 days of follow-up

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Uganda Malaria Surveillance Project; Ministry of Health, Uganda
• Investigators: Principal Investigator: Sarah G Staedke, MD, London School of Hygiene and Tropical Medicine

Publications and helpful links

General Publications

• Nankabirwa J, Cundill B, Clarke S, Kabatereine N, Rosenthal PJ, Dorsey G, Brooker S, Staedke SG. Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren. PLoS One. 2010 Oct 19;5(10):e13438. doi: 10.1371/journal.pone.0013438.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: February 7, 2008
• First Submitted That Met QC Criteria: February 26, 2009
• First Posted (Estimated): February 27, 2009

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Malaria; Tolerability; Intermittent preventive treatment; Schoolchildren; Uganda
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Pyrimethamine; Piperaquine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine; Artenimol
• Other Study ID Numbers: ITCRVG49; LSHTM Ethics 5197 (Other Identifier: London School of Hygiene and Tropical Medicine)

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