Serological Screen and Treat Trial for Plasmodium Vivax

Malaria, Vivax Clinical Trial

— SSAT  

Official title:

Serological Screen and Treat Trial for P. Vivax: a Proof-of-concept Trial in Western Indonesia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04223674
• Other study ID #: 19-09-1129
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 9, 2022
• Est. completion date: December 30, 2023

Study information

• Verified date: March 2023
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1133
• Est. completion date: December 30, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Malaria, Vivax

Intervention

Diagnostic Test:
• Serological screen and treat
Multi-antigen sero-diagnostic test for measurement of P. vivax antibodies in plasma from finger stick as a means to detect hypnozoite carriers for treatment

Locations

Country	Name	City	State
Indonesia	Tanjung Tiram Primary Health Center	Tanjung Tiram	Batubara

Sponsors (6)

Lead Sponsor	Collaborator
Indonesia University	Eijkman Institute for Molecular Biology, Eijkman Oxford Clinical Research Unit, Indonesia, Rumah Sakit Umum Daerah Mimika, Universitas Sumatera Utara, Walter and Eliza Hall Institute of Medical Research

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence reduction	Difference of P. vivax incidence by PCR between children serologically screened and those receiving routine care.	9 month of follow up
Secondary	Time-to recur	Difference in the time-to recur of P. vivax by PCR in SSAT and control arms.	9 month
Secondary	Recurrence number	Difference in the number of recurrent P. vivax by PCR in SSAT vs. control arms	9 month
Secondary	Recurrent symptomatic P. vivax	Difference in the incidence of recurrent symptomatic P. vivax by microscopy in SSAT vs control arms	9 month
Secondary	Seroconversion rate	Seroconversion rate before and after intervention in SSAT and control arms.	9 month
Secondary	point-of-care assay performance	Sensitivity and specificity of point-of-care antibody detection test vs. gold standard Luminex assay	one month
Secondary	Adverse event and severe adverse event	Adverse event (AE) and Severe Adverse Event (SAE) of high dose PQ in schoolchildren.	9 month
Secondary	Sahli Hb	Hb level in Sahli's method, Standard G6PD (SD Biosensor Inc., ROK) in comparison with (HemoCue AB, Angelholm, Sweden).	One month
Secondary	Skin gametocyte	Sensitivity and specificity of microscopic examination to detect parasitemia from the shallow skin vasculature of the ankle (light microscopy-skin/LMS) compared to standard microscopic (light microscopy-finger/LMF) and PCR.	9 month
Secondary	Gametocyte duration	Mean duration time of gametocyte in LMS and LMF	9 month
Secondary	Hemozoin detection	Sensitivity and specificity of magneto-optical hemozoin detection (MOD) compared to standard malaria detection and PCR.	One month