Intermittent Preventive Treatment of Malaria in Schoolchildren

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 3

Conditions: Malaria; Intermittent Preventive Treatment

Treatments: Drug: sulfadoxine-pyrimethamine; Drug: amodiaquine + sulfadoxine-pyrimethamine; Drug: dihydroartemisinin-piperaquine; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00852371

LSHTM Ethics 5197 (Other Identifier)

ITCRVG49

Details and patient eligibility

About

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.

Full 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.

Enrollment: 780 patients

Sex: All

Ages: 8 to 13 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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780 participants in 4 patient groups, including a placebo group

Combination of Amodiaquine +sulfadoxine-pyrimethamine

Active Comparator group

Description:

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

Treatment:

Drug: amodiaquine + sulfadoxine-pyrimethamine

Dihydroartemisinin-piperaquine

Active Comparator group

Description:

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)

Treatment:

Drug: dihydroartemisinin-piperaquine

Placebo

Placebo Comparator group

Description:

Placebo (had no active ingredients, produced by Cosmos Limited, Nairobi, Kenya)

Treatment:

Other: Placebo

Sulfadoxine-pyrimethamine alone

Active Comparator group

Description:

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

Treatment:

Drug: sulfadoxine-pyrimethamine