Clinical trial NCT04223674: Serological Screen and Treat Trial for Plasmodium Vivax
Official title: Serological Screen and Treat Trial for P. Vivax: a Proof-of-concept Trial in Western Indonesia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malaria, Vivax
Keywords: serology
screen
treat
recurrent
vivax
Lead sponsor: Indonesia University
Sponsor class: OTHER
Collaborators: name: Eijkman Institute for Molecular Biology
name: Eijkman Oxford Clinical Research Unit, Indonesia
name: Walter and Eliza Hall Institute of Medical Research
name: Rumah Sakit Umum Daerah Mimika
name: Universitas Sumatera Utara
First posted: 2020-01-10
Enrollment: 1133
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study evaluates an experimental serological diagnostic technique intended to identify people at high risk of having dormant malaria parasites in their liver.

960 children living in western Indonesia will be individually randomised to the experimental serologic test or routine care.

Children in the serological diagnosis arm will be screened for the presence of antibodies to a previously validated panel of malaria antigens optimized for sensitivity to infection during the prior 9 months. Furthermore, they also will be screened by microscopy. If positive by either test, they will be treated for that malaria infection.

Children assigned to routine care will be screened by microscopic examination and treated when they show or have history of symptoms in the last 3 days.

After initial screening and treating according to diagnostic technique, all children will be actively followed for 9 months with PCR detection every 4 weeks.
Primary purpose: SCREENING

Brief summary: This is a clinical trial to evaluate an experimental serological diagnostic technique intended to identify people at high risk of having dormant malaria parasites in their liver. The study is designed to evaluate the efficacy of serological screening vs. routine care for the prevention of recurrent P. vivax infections. A total of 960 schoolchildren will be randomized into the interventional or control arm.

Detailed description: This is a randomized controlled trial to evaluate an experimental serological diagnostic technique intended to identify people at high risk of having dormant malaria parasites in their liver. The study is designed to show a superiority of SSAT vs. routine care for the prevention of recurrent P. vivax infections. With the estimated prevalence of 20%, the investigators will have a power of \>90% to detect a significant difference with the sample size of 350 children per group. The investigators will recruit 480 children per group to anticipate subject loss due to exclusion and drop out.

After obtaining informed consent from their parents/legal guardians, 800 schoolchildren living in Batubara regency, North Sumatra, Indonesia, will be individually randomized to intervention (SSAT) or control (routine care) group. During enrollment, all participants will be tested with Pv serological test by standard Luminex, and standard finger stick microscopic. Their hemoglobin (Hb) and Glucose-6-Phosphate Dehydrogenase (G6PD) level will be measured. Children with Hb level\<9 g/dL and/or G6PD \<4 U/g Hb (male) or \<6 U/g Hb (female) will be excluded. In the intervention arm (SSAT), children who are seropositive by standard Luminex and/or symptomatic LMF positive will be treated with dihydroartemisinin-piperaquine (DHA-PP) for 3 days according to national guideline and primaquine/PQ high dose (1 mg/kg BW/day for 7 days for Pv/Po, 0.25 mg/kg BW for Pf). In the control arm, children will be treated only when they show symptoms (body temperature\>=36.5oC or history of fever within last 3 days) and proven positive by LMF. All treatment will be provided under direct supervision by the research team during which any adverse event/severe adverse event will be recorded. Hemoglobin level and urine will be monitored daily for 7 days of PQ administration. Post-hoc qPCR detection will be performed to determine their initial malaria status. Several additional tests will also be performed to all participants during this initial screening: microscopic examination of shallow vasculature of the ankle (light microscopy-skin/LMS), magneto-optical detection of hemozoin, and post-hoc point-of-care/POC serological test.

After enrollment, all children will be actively followed for 9 months every 4 weeks for post-hoc assessment by qPCR. Anytime during this follow up period, children becoming acutely ill will be tested for malaria by LMF, and referred to Primary Health Center to receive treatment when positive. Furthermore, household members of these infected children will also be screened for malaria infection by LMF and post-hoc LMS and qPCR. This family screening will be performed by 2x house visit (7-10 AM and 7-10 PM). Treatment will be given for those found positive by LMF regardless of their symptoms. Antimalarial treatment provided during this follow up period will be according to national standard guideline: 3 days of DHA-PP plus PQ (single 0.25 mg/kg BW dose for Pf, daily 0.25 mg/kg BW dose for 14 days for Pv/Po).

At the end of study, Pv serological test and LMF will be performed to all schoolchildren. Those found positive by LMF will be referred to Primary Health Center to receive treatment according to national standard guideline.

Sponsor: WEHI, Funding: NHMRC, Grant number: GNT1102297

Eligibility criteria: Inclusion Criteria:

* resident of study area and attending selected elementary school in Grade 1-5 or middle school Grade 1-3
* no evidence of health condition that would interfere with study participation
* assent of child and documented parental informed consent

Exclusion Criteria:

* G6PD deficiency as determined by SD Biosensor quantitative determination of \<70% G6PD activity (\<6 U/g Hb).
* Haemoglobin \< 9 g/dL

Primary outcomes:
measure: Incidence reduction
timeFrame: 9 month of follow up
Secondary outcomes:
measure: Time-to recur
timeFrame: 9 month
measure: Recurrence number
timeFrame: 9 month
measure: Recurrent symptomatic P. vivax
timeFrame: 9 month
measure: Seroconversion rate
timeFrame: 9 month
measure: point-of-care assay performance
timeFrame: one month
measure: Adverse event and severe adverse event
timeFrame: 9 month
measure: Sahli Hb
timeFrame: One month
measure: Skin gametocyte
timeFrame: 9 month
measure: Gametocyte duration
timeFrame: 9 month
measure: Hemozoin detection
timeFrame: One month
Other outcomes:
Locations:
city: Tanjung Tiram
country: Indonesia
facility: Tanjung Tiram Primary Health Center
state: Batubara
Study officials:
affiliation: Indonesia University
name: Inge Sutanto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: