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

NCT03640403 | Completed Phase 3 DMC

• 1 other identifier: TEAM VERSION3
• Study Type: interventional
• Target: 1,555
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria,Falciparum; Anemia

Keywords

Malaria; school children; randomized controlled trial; safety; effectiveness; Dihydroartemisinin-piperaquine; cognitive; Artesunate-amodiaquine; malaria serology; drug resistance

Outcome Measures

Primary Outcomes (2)

• Change from baseline in mean haemoglobin concentration at months 12 and 20 of follow-up

  Will measure change from baseline haemoglobin concentration at month 12 (intervention period) and at month 20 (post intervention period to assess rebound effect) \[Note: a trend of change at each visit will also be assessed with respect to malaria seasonality\]

  at months 0, 12 and 20

• Clinical malaria incidence from month 0 till months 12 and 20 of follow up

  number of symptomatic malaria episodes during and after intervention period

  at months 0, 12 and 20

Secondary Outcomes (9)

• Prevalence of asymptomatic malaria infections at month 0, 12 and 20 of follow up

  from month 0 till month12 and 20

• Prevalence of PCR confirmed sub-microscopic parasitaemia at months 0,12 and 20 of follow up

  at months 0, 12 and 20

• Prevalence of soil transmitted helminths and schistosomiasis

  at baseline, at month 12 and month 20.

• Prevalence of schistosomiasis

  at baseline, at month 12 and month 20.

• Prevalence of validated common P. falciparum polymorphisms known to be associated with drug sensitivity at baseline, at months 12 and 20

  at baseline, at month 12 and 20.

Other Outcomes (6)

• number of days missed school attendance pre and post intervention period

  at baseline, at month 12 and 20

• Change in educational performance

  at baseline, at month 12 and 20

• change in sustained attention on cognition evaluated using two code transmission tasks using TEA-Ch

  evaluated at baseline, at month 12 and 20.

Study Arms (3)

DP

EXPERIMENTAL

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.

Drug: Dihydroartemisinin-piperaquine

ASAQ

ACTIVE COMPARATOR

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.

Drug: Artesunate-amodiaquine

Control

NO INTERVENTION

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

Interventions

Dihydroartemisinin-piperaquine DRUG

Dihydroartemisinin-piperaquine (DP). One of the Artemisinin combination therapy(ACTs), indicated for treatment of uncomplicated malaria. It will to be given every 4 months 3 rounds for a year.

DP

Artesunate-amodiaquine DRUG

Artesunate-amodiaquine (ASAQ). One of the Artemisinin combination therapy(ACTs), indicated for treatment of uncomplicated malaria. It will to be given every 4 months 3 rounds for a year.

ASAQ

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute for Medical Research, Tanzania: lead
• Universiteit Antwerpen: collaborator

Study Sites (1)

National Institute for Medical Research

Tanga, 255, Tanzania

Location

Related Publications (3)

• Hhera JJ, Makenga G, Baraka V, Francis F, Nakato S, Gesase S, Mtove G, Madebe R, Kyaruzi E, Minja DTR, Lusingu JPA, Van Geertruyden JP. Malaria-malnutrition interaction: prevalence, risk factors, and the impact of intermittent preventive therapy for malaria on nutritional status of school-age children in Muheza, Tanga, Tanzania - A cross-sectional survey and a randomized controlled open-label trial. BMC Public Health. 2025 Aug 13;25(1):2754. doi: 10.1186/s12889-025-23315-w.

  PMID: 40804388 DERIVED

• Makenga G, Baraka V, Francis F, Nakato S, Gesase S, Mtove G, Madebe R, Kyaruzi E, Minja DTR, Lusingu JPA, Geertruyden JV. Effectiveness and safety of intermittent preventive treatment with dihydroartemisinin-piperaquine or artesunate-amodiaquine for reducing malaria and related morbidities in schoolchildren in Tanzania: a randomised controlled trial. Lancet Glob Health. 2023 Aug;11(8):e1277-e1289. doi: 10.1016/S2214-109X(23)00204-8.

  PMID: 37474234 DERIVED

• Makenga G, Baraka V, Francis F, Nakato S, Gesase S, Mtove G, Madebe R, Kyaruzi E, Minja DTR, Lusingu JPA, Van Geertruyden JP. 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: A study protocol for a controlled randomised trial. Contemp Clin Trials Commun. 2020 Feb 20;17:100546. doi: 10.1016/j.conctc.2020.100546. eCollection 2020 Mar.

  PMID: 32382685 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Anemia; Malaria

Interventions

amodiaquine, artesunate drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• John PA Lusingu, MD, PhD

  National Institute for Medical Research, Tanzania

  PRINCIPAL INVESTIGATOR

• Jean-pierre Van geertruyden, MD, PhD

  Global health institute, University of Antwerp, Belgium.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A randomized, controlled, open label study assessing the effectiveness and safety of 2 antimalarial drugs for IPTsc, namely DP and ASAQ by a 3-arm trial using a "balanced block design" with the "standard of care" arm as reference.

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 21, 2018
• Study Start: March 26, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2021
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

TA (1)