Clinical trial NCT02001428: Malaria in Early Life Study
Official title: Intermittent Screening and Treatment for the Control of Malaria in the First Year of Life in Papua, Indonesia: A Cluster Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Plasmodium Falciparum Malaria
Plasmodium Vivax Malaria
Keywords: malaria
vivax
falciparum
infants
Lead sponsor: Gadjah Mada University
Sponsor class: OTHER
Collaborators: name: Timika Research Facility, Indonesia
name: Eijkman Institute for Molecular Biology
name: Menzies School of Health Research
First posted: 2013-12-04
Enrollment: 757
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effectiveness of different malaria control strategies in the first year of life.

The effectiveness of delivering an intermittent screening and treatment programme with dihydroartemisinin-piperaquine (DHP), linked to local immunization programmes, will be compared to the current practice of passive case detection of malaria.

This study has two objectives:

1. To assess the effectiveness of intermittent screening and treatment with dihydroartemisinin-piperaquine (DHP) administered at 2, 3, 4 and 9 months of age compared with the current practice of passive detection and treatment for malaria in an area with high drug resistance levels to both P. falciparum and P. vivax.
2. To evaluate the safety, efficacy and population pharmacokinetics of DHP in children under 1 year of age.

Detailed description: Infant malaria is a major public health issue in Timika, Papua (Indonesia) and the risk starts at birth with the majority of malaria, mostly asymptomatic, in the first 3 days of life. Malaria infection is associated with severe complications, such as severe anaemia and respiratory distress, and can be fatal.

The emergence of multidrug resistant malaria poses a significant health risk to this vulnerable group. In addition, due to non-specific symptoms of malaria found in this age group, the diagnosis is often missed. Early detection and prompt treatment with an effective antimalarial drug is the key to prevent adverse outcomes from malaria in the first year of life.

The first line treatment for uncomplicated malaria in Indonesia is Dihydroartemisinin-piperaquine (DHP), an ACT that has been shown to be highly efficacious in this region, although experience of its use in infants less than one year old is limited.

Although the World Health Organization recommends antimalarial drug efficacy trials in infants, most ACT efficacy studies include children aged one year or older. Drug population pharmacokinetic studies have enrolled younger infants aged 5-6 months old, whereas Intermittent Preventive Treatment in Infants (IPTi) studies usually start with infants as young as 3 months old.

In view of the challenges to identifying an effective malaria treatment for infants in Indonesia, the proposed study has been designed to evaluate the effectiveness of delivering early detection and prompt treatment with DHP at 2, 3, 4 and 9 months of age, linked to local immunization programmes delivered at village health posts (Posyandu), in an area with high drug resistance levels to both P. falciparum and P. vivax. The effectiveness of this approach will be compared to the current practice of passive case detection. We will also define the efficacy and pharmacokinetic profile of DHP in infancy and monitor the safety and toxicity of its use.

The proposed study will enrol 756 infants across 5 health centres in Papua, Indonesia. Infants will be recruited from pregnant mothers who are enrolled as participants of the concurrent STOPMiP trial - a clinical research study which aims to evaluate intermittent screening and treatment (IST) or intermittent preventive therapy (IPT) with DHP in pregnant women in Indonesia.

The trial result will inform policy makers in Indonesia, and internationally, on the effectiveness of different malaria control strategies in the first year of life.

Eligibility criteria: Inclusion Criteria:

* Mother of participant is enrolled in the STOP MiP trial
* Healthy full term newborn of consenting parent
* Residence in the study area for the duration of the follow up period

Exclusion Criteria:

* Preterm infants (\<37 weeks gestation)
* Sick newborns, requiring hospitalization

Primary outcomes:
measure: The incidence of clinical malaria in the first year of life
timeFrame: Total number of new clinical cases per child during the first year of life
Secondary outcomes:
measure: Proportion of infant with recurrent parasitaemia due to any species at day 42 after treatment with DHP.
timeFrame: Parasitaemia found at day 42 after treatment with DHP
Other outcomes:
measure: Prevalence of anaemia and malaria at 6 and 12 months of age.
timeFrame: Prevalence will be assessed at 6 and 12 months of age
measure: Population mean pharmacokinetic profile of Piperaquine
timeFrame: the piperaquine level will be assessed at day 0,1,2,7,14,21,28,35 and 42 after treatment with DHP
Locations:
city: Timika
country: Indonesia
facility: Timika Research Facility
state: Papua
Study officials:
affiliation: University of Gadjah Madah
name: Jeanne R Poespoprodjo, MD, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Poespoprodjo JR, Hafiidhaturrahmah, Sariyanti N, Indrawanti R, McLean ARD, Simpson JA, Kenangalem E, Burdam FH, Noviyanti R, Trianty L, Fadhilah C, Soenarto Y, Price RN. Intermittent screening and treatment for malaria complementary to routine immunisation in the first year of life in Papua, Indonesia: a cluster randomised superiority trial. BMC Med. 2022 Jun 8;20(1):190. doi: 10.1186/s12916-022-02394-1.