Serological Screen and Treat Trial for Plasmodium Vivax (SSAT)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria, Vivax
• Intervention / Treatment: Diagnostic test: Serological screen and treat

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

• Study Type: Interventional
• Enrollment (Actual): 1133
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • Batubara
    • Tanjung Tiram, Batubara, Indonesia, 21253
      • Tanjung Tiram Primary Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 15 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Serological screen and treat; Children who screened with sero test and microscopy. A 7-day high dose PQ will be provided for those with Pv seropositive regardless of their symptoms and symptomatic children with microscopic Pv/Po positive.	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
No Intervention: Routine care; Children who screened with sero test and microscopy. A 7-day high dose PQ will be provided only for symptomatic children with microscopic Pv/Po positive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence reduction	Difference of P. vivax incidence by PCR between children serologically screened and those receiving routine care.	9 month of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to recur	Difference in the time-to recur of P. vivax by PCR in SSAT and control arms.	9 month
Recurrence number	Difference in the number of recurrent P. vivax by PCR in SSAT vs. control arms	9 month
Recurrent symptomatic P. vivax	Difference in the incidence of recurrent symptomatic P. vivax by microscopy in SSAT vs control arms	9 month
Seroconversion rate	Seroconversion rate before and after intervention in SSAT and control arms.	9 month
point-of-care assay performance	Sensitivity and specificity of point-of-care antibody detection test vs. gold standard Luminex assay	one month
Adverse event and severe adverse event	Adverse event (AE) and Severe Adverse Event (SAE) of high dose PQ in schoolchildren.	9 month
Sahli Hb	Hb level in Sahli's method, Standard G6PD (SD Biosensor Inc., ROK) in comparison with (HemoCue AB, Angelholm, Sweden).	One month
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
Gametocyte duration	Mean duration time of gametocyte in LMS and LMF	9 month
Hemozoin detection	Sensitivity and specificity of magneto-optical hemozoin detection (MOD) compared to standard malaria detection and PCR.	One month

Collaborators and Investigators

• Sponsor: Indonesia University
• Collaborators: Universitas Sumatera Utara; Eijkman Institute for Molecular Biology; Eijkman Oxford Clinical Research Unit, Indonesia; Walter and Eliza Hall Institute of Medical Research; Rumah Sakit Umum Daerah Mimika
• Investigators: Principal Investigator: Inge Sutanto, MD, PhD, Indonesia University

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2022
• Primary Completion (Anticipated): May 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 4, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: vivax; recurrent; serology; screen; treat
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Vivax
• Other Study ID Numbers: 19-09-1129

Plan for Individual participant data (IPD)

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

IPD Plan Description

What data that will be shared:

Only fully anonymized data sets will be shared as required for transparency and to fulfil publication requirements.

Who will have access to the data:

Researcher who provide a methodologically sound proposal.

Where will the data be available:

The data will be available upon request.

When will the data be shared:

Immediately following publication. No end date.

How will researchers locate and access the data:

Proposal should be sent to akosasih@eocru.org as the Study Coordinator of the trial. To gain access, data requestor will need to sign data access agreement.

• IPD Sharing Time Frame: No end date
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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