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Intermittent Preventive Treatment of Malaria in Schoolchildren

Phase 3
Completed
Conditions
Intermittent Preventive Treatment
Malaria
Interventions
Registration Number
NCT00852371
Lead Sponsor
London School of Hygiene and Tropical Medicine
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
780
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Combination of Amodiaquine +sulfadoxine-pyrimethamineamodiaquine + sulfadoxine-pyrimethamineCombination 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
Dihydroartemisinin-piperaquinedihydroartemisinin-piperaquineDihydroartemisinin-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)
PlaceboPlaceboPlacebo (had no active ingredients, produced by Cosmos Limited, Nairobi, Kenya)
Sulfadoxine-pyrimethamine alonesulfadoxine-pyrimethaminesulfadoxine-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
Primary Outcome Measures
NameTimeMethod
Risk of Parasitaemia (Unadjusted by Genotyping)after 42 days of follow-up

Proportion of participants whose thick blood smears that are positive for asexual parasites

Secondary Outcome Measures
NameTimeMethod
Acceptability of IPT Regimenson day 7

Perceived willingness to take study medication as routine preventive treatment

Risk of Recrudescence (Adjusted by Genotyping) in Participants Who Were Parasitaemic at Enrollmentafter 42 days of follow-up

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

Risk of New Infection (Adjusted by Genotyping) in All Participantsafter 42 days of follow-up

Proportion of participants whose thick blood smears that are positive for new asexual parasites on day of failure at genotyping

Risk of Clinical Failure Due to Recrudescence (Adjusted by Genotyping) in Children Who Were Parasitaemic at Enrollmentafter 42 days of follow-up

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

Mean Change in HaemoglobinBetween day 0 to day 42

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

Risk of Serious Adverse Eventsover 42 days of follow-up

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

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