Evaluation of the Implementation and Effectiveness of Intermittent Preventive Treatment for Malaria Using Dihydroartemisinin-piperaquine on Reducing Malaria Burden in School Aged Children in Tanzania (IPTsc)

In Tanzania, according to the National Malaria Control Programme (NMCP), malaria prevalence has declined from an average of 18.1% in 2008 to 7% in 2017, marked as an epidemiological transition from meso-endemic to hypo-endemic levels with variation across and within regions and/or councils. Children of school-age have become increasingly more vulnerable as compared to those aged less than five years. In high-transmission settings, up to 70% of school-aged children harbour malaria parasites which is mostly asymptomatic, accounting for around 50% of the mortality, 13-50% of all school absenteeism. The NMCP developed a supplementary malaria midterm strategic plan (SMMSP 2018-2020) to customise malaria interventions by stratifying the burden of malaria in Tanzania mainland and recommended use of Dihydroartemisinin-Piperaquine (DP) for intermittent preventive treatment in school children (IPTsc) in high malaria strata. The investigators plan to evaluate the implementation of IPTsc using DP, given three times a year, for evidence on the operational feasibility and effectiveness of IPTsc on clinical malaria incidence at a high endemic area in Handeni District Council (DC), Handeni Town Council (TC) and Kilindi DC of Tanga region, Tanzania.

The study is an effectiveness-implementation hybrid trial to assess feasibility and effectiveness of IPTsc using DP against standard of care (control). Wards in the three study districts (Handeni DC, Handeni TC and Kilindi DC) will be the randomisation unit (clusters). Each ward will be randomised to implement IPTsc or not (control). In all wards in the IPTsc arm, the interventional drugs (DP) will be given at an interval of four months, three times a year. For study evaluation of the impact of intervention, in each district representative randomly selected wards, will provide randomly selected school per ward (24 in total) to formulate part of evaluable children per intervention. Mixed design methods will be used to assess the feasibility and acceptability of implementing IPTsc as part of a more comprehensive school children health package.

The study is expected to be operationally feasible given existing school health programme for Neglected Tropical Disease (NTD) control and the school net programme (SNP). IPTsc is expected to increase malaria case management effectiveness and to have additional effect in reducing the burden of disease on top of optimal access to malaria case management (MCM) and malaria vector control (MVC) initiatives e.g. early diagnosis and treatment, and insecticide-treated nets (ITNs) coverage, respectively.

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: Dihydroartemisinin-Piperaquine (DP)

• Study Type: Interventional
• Enrollment (Actual): 4100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tanzania
  • Tanga, Tanzania
    • Handeni Town Council, Handeni and Kilindi Districts

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The following eligibility criteria are used to enroll participants on for close monitoring follow ups assessing the effectiveness part of the study protocol.

Inclusion Criteria:

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

Exclusion Criteria:

1. Students at class 7
2. Currently enrolled in another study or participated in another investigational drug study within the last 30 days.
3. Known to have heart disease or a known cardiac ailment.
4. Reports known hypersensitivity to the study drugs.
5. Not willing to undergo all study procedures including physical examination and to provide blood samples as per this study protocol.
6. Having clinical features of severe anaemia
7. Febrile due to non-malaria illness at the time of recruitment.
8. Has apparent severe infection or any condition that requires hospitalization
9. 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.
10. Body weight < 12 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IPTsc arm; Dihydroartemisinin-Piperaquine (DP) for intermittent preventive treatment in school children (IPTsc) will be given in all wards in the IPTsc arm at an interval of four months, three times a year.	Drug: Dihydroartemisinin-Piperaquine (DP); Dihydroartemisinin-Piperaquine (DP) for intermittent preventive treatment of malaria in school children (IPTsc).
No Intervention: Control; No intervention will be given to wards randomised in this arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficiency of school health teachers to deliver antimalarial drugs to school children in high endemic regions	Efficiency in terms of percentage of children given a complete dose in each round.	1 year from start of intervention
Clinical malaria incidence	Malaria incidence will be collected in terms of number of episodes a child gets malaria.	from month 0 till month 12 of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in malaria incidence per 1000 population at local health facility level	Number of malaria episodes before and after intervention in a respective ward	from month 0 till month 12 of follow up
Change from baseline in haemoglobin concentration	individual change in Haemoglobin before and after intervention	measured at month 12
Number of participants with treatment-related adverse events	Number of participants with treatment-related adverse events encountered by subjects per study arm	through study completion, an average of 1 year"
Cardio safety profile by QTc prolongation from baseline	measured by ECG	Day 1, 2,3 and 7 after before and after dosing
Acceptability of IPTsc in communities with high malaria endemicities	Through in depth interview in a guided questionnaire	At month 8 of implementation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of school children with malnutrition	Weight and height will be combined to report BMI in kg/m^2, WHO's BMI z-score will be used to categorise nutrition status.	at month 0 (baseline) and at month 12.

Collaborators and Investigators

• Sponsor: National Institute for Medical Research, Tanzania
• Collaborators: National Malaria Control Program, Tanzania
• Investigators: Study Director: John P.A Lusingu, MD, PhD, National Institute for Medical Research, Tanga, Tanzania; Study Director: Ally Mohamed, MD, National Malaria Control Programme, Tanzania; Principal Investigator: Geofrey Makenga, MD, Msc, PhD fellow, National Institute for Medical Research, Tanzania

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2020
• Primary Completion (Actual): May 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Piperaquine; Artenimol
• Other Study ID Numbers: IPTsc version 1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No