Clinical trial NCT03640403: 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
Official title: 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 Controlled Randomised Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria,Falciparum
Anemia
Keywords: Malaria
school children
randomized controlled trial
safety
effectiveness
Dihydroartemisinin-piperaquine
cognitive
Artesunate-amodiaquine
malaria serology
drug resistance
Lead sponsor: National Institute for Medical Research, Tanzania
Sponsor class: OTHER_GOV
Collaborators: name: Universiteit Antwerpen
First posted: 2018-08-21
Enrollment: 1555
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in mean haemoglobin concentration at months 12 and 20 of follow-up
timeFrame: at months 0, 12 and 20
measure: Clinical malaria incidence from month 0 till months 12 and 20 of follow up
timeFrame: at months 0, 12 and 20
Secondary outcomes:
measure: Prevalence of asymptomatic malaria infections at month 0, 12 and 20 of follow up
timeFrame: from month 0 till month12 and 20
measure: Prevalence of PCR confirmed sub-microscopic parasitaemia at months 0,12 and 20 of follow up
timeFrame: at months 0, 12 and 20
measure: Prevalence of soil transmitted helminths and schistosomiasis
timeFrame: at baseline, at month 12 and month 20.
measure: Prevalence of schistosomiasis
timeFrame: at baseline, at month 12 and month 20.
measure: Prevalence of validated common P. falciparum polymorphisms known to be associated with drug sensitivity at baseline, at months 12 and 20
timeFrame: at baseline, at month 12 and 20.
measure: Proportion of children seropositive for Plasmodium falciparum AMA-1 and MSP-119 at baseline, at month 12 and 20
timeFrame: at baseline, at month 12 and 20.
measure: Change in serum antibody responses to Plasmodium falciparum AMA-1 and MSP-119 at baseline, at month 12 and 20
timeFrame: at baseline, at month 12 and 20.
measure: Percentages of school children with malnutrition through WHO's BMI z-score
timeFrame: at month 0, 12, and 20
measure: Relative risk (RR), for all adverse events categorised to severity at month 12 and 20
timeFrame: at month 12 and 20
Other outcomes:
measure: number of days missed school attendance pre and post intervention period
timeFrame: at baseline, at month 12 and 20
measure: Change in educational performance
timeFrame: at baseline, at month 12 and 20
measure: change in sustained attention on cognition evaluated using two code transmission tasks using TEA-Ch
timeFrame: evaluated at baseline, at month 12 and 20.
measure: change in psychomotor functions tested by 20mShuttle Run Test pre and post intervention
timeFrame: evaluated at baseline, at month 12 and 20.
measure: Proportion of participants accepting IPTsc, using and completing dose of given study drugs.
timeFrame: at baseline, month 4, and 8
measure: Comparison of cost effectiveness of intervention between groups.
timeFrame: at month 12.
Locations:
city: Tanga
country: Tanzania
facility: National Institute for Medical Research
Study officials:
affiliation: National Institute for Medical Research, Tanzania
name: John PA Lusingu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Global health institute, University of Antwerp, Belgium.
name: Jean-pierre Van geertruyden, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.