Effectiveness and Safety of Intermittent Preventive Treatment for Malaria Using Either Dihydroartemisinin-piperaquine or Artesunate-amodiaquine in Reducing Malaria Related Morbidities and Improving Cognitive Ability in School-aged Children in Tanzania (InSMART-school)

National Institute for Medical Research, Tanzania

Status and phase: Completed; Phase 3

Conditions: Anemia; Malaria,Falciparum

Treatments: Drug: Dihydroartemisinin-piperaquine; Drug: Artesunate-amodiaquine

Study type: Interventional

Funder types: Other

Identifiers

NCT03640403

TEAM VERSION3

Details and patient eligibility

About

Background:

In high-transmission settings, up to 70% of school-aged children harbour malaria parasites which is mostly asymptomatic, thus, from an epidemiological point of view, they contribute significantly as reservoir to onward malaria transmission to others. In endemic areas, malaria accounts for around 50% of the mortality, 13-50% of all school absenteeism, and causes anaemia in approximately 85 million school-aged children of sub Saharan Africa that also impairs the cognitive development of children. Intermittent preventive treatment (IPT) of pregnant women as well as seasonal malaria chemoprevention in children under the age of five have been implemented in several sub-Saharan countries and have proven to be very effective. However, none of these IPT strategies is targeting school children. A clinical trial is being conducted to expand the IPT by testing effectiveness and safety of two antimalarial drugs Dihydroartemisinin-piperaquine (DP) and Artesunate-amodiaquine (ASAQ) in preventing malaria related morbidity in school aged children (IPTsc) living in high endemic areas.

Methods:

A randomized, open label, controlled trial will enrol 1602 school children aged 5-15 years, who will receive either DP or ASAQ or control (no drug ), using a "balanced block design" with the "standard of care" arm as reference. The interventional treatments are given every 4 months 3 rounds for the first year. A second non-interventional year will assess possible rebound effects. All study-arms receive bed nets, early diagnosis and care for malaria, and praziquantel and albendazole as mass treatment for helminthiasis. The primary endpoint are change from baseline in mean haemoglobin concentration at months 12 and 20 of follow-up and clinical malaria incidence from month 0 till months 12 and 20 of follow up. Adverse events will be monitored throughout the study. Mixed design methods will be used to assess the acceptability, cost-effectiveness and feasibility of this IPTsc as part of a more comprehensive school children health package.

Discussion:

The national school health programme (NSHP), Tanzania, combines schistosomiasis and soil transmitted helminthes (STH) control package under national schistosomiasis and STH control programme (NSSCP). Malaria intervention using IPTsc strategy may be integrated in NSHP with the same platform as NSSCP, however, there is limited systematic evidence to assess the operational feasibility of this approach. School aged children are a reachable target population in any endemic malaria setting. The suggested strategy will provide effective protection against malaria, hasten either the elimination process and/or diminish the reservoir and burden.

Enrollment: 1,555 patients

Sex: All

Ages: 5 to 15 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Includes parental/guardian informed consent
• Assent by primary school children aged 11 years and above.
• Aged 5-15 years.
• Currently, lives within the pre-defined catchment area of Muheza District.
• Will remain within the same area throughout the study period (preferably class five and below).

Exclusion criteria

• Students at class 6 and 7
• Currently enrolled in another study or participated in another investigational drug study within the last 30 days.
• Known to have heart disease or a known cardiac ailment.
• Reports known hypersensitivity to the study drugs.
• Not willing to undergo all study procedures including physical examination and to provide blood samples as per this study protocol.
• Having clinical features of severe anaemia
• Febrile due to non-malaria illness at the time of recruitment.
• Has apparent severe infection or any condition that requires hospitalization
• Illness or conditions like hematologic, cardiac, renal, hepatic diseases which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency and SS sickle cell.
• Body weight < 14 k

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,555 participants in 3 patient groups

DP

Experimental group

Description:

Dihydroartemisinin-piperaquine (DP), antimalarial drug to be given every 4 months 3 rounds for the first year. A second non-interventional year will assess possible rebound effects.

Treatment:

Drug: Dihydroartemisinin-piperaquine

ASAQ

Active Comparator group

Description:

Artesunate-amodiaquine (ASAQ), antimalarial drugs to be given every 4 months 3 rounds for the first year. A second non-interventional year will assess possible rebound effects.

Treatment:

Drug: Artesunate-amodiaquine

Control

No Intervention group

Description:

No intervention drugs will be given, but normal routine standard of care will be provided.