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Trial registered on ANZCTR


Registration number
ACTRN12621000963820
Ethics application status
Approved
Date submitted
18/06/2021
Date registered
23/07/2021
Date last updated
23/07/2021
Date data sharing statement initially provided
23/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Focal case detection surveillance of asymptomatic malaria and its treatment in Gia Lai and Phu Yen provinces of Central Vietnam
Scientific title
Focal case detection surveillance of asymptomatic malaria and its treatment in Gia Lai and Phu Yen provinces of Central Vietnam
Secondary ID [1] 304520 0
VDCP02 Version 1 (02 April 2021)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 322386 0
Condition category
Condition code
Infection 320047 320047 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Focal case detection surveillance for asymptomatic malaria and its treatment of P. falciparum malaria with the first-line artemisinin-based combination therapy, a standard 3-day course of Pyramax® (pyronaridine-artesunate) plus a single oral dose of primaquine or a 3-day course of chloroquine plus a 14 day course of primaquine for P. vivax malaria for people living and working in selected communes in Krong Pa district (Gia Lai province) and Song Hinh district (Phu Yen province).

People (up 1200) without symptoms of malaria such as fever, headache, nausea and fatigue will be invited to provide a finger prick blood sample (0.25 mL) for reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of malaria infections. Asymptomatic participants diagnosed by RT-qPCR to be infected with P. falciparum will be treated with pyronaridine-artesunate to kill the blood asexual stages. Each tablet of pyronaridine-artesunate contains 60 mg artesunate + 180 mg pyronaridine. The dose of pyronaridine-artesunate will be in accordance to the participant's body weight with the target dosage range for pyronaridine–artesunate of 15.0 to 8.3 mg/kg/day of body weight for pyronaridine and 5.0 to 2.5 mg/kg/day of body weight for artesunate. Pyronaridine–artesunate will be administered orally, at about 24 hour intervals for the 3 consecutive days. Also, on the first day of treatment patients will be coadministered a single oral dose of primaquine (0.5 mg/kg, each tablet contains 7.5 mg base of primaquine) to kill sexual stages of falciparum malaria to prevent transmission. Pyronaridine-artesunate and primaquine dosing will be observed and recorded in the participant's case report form (CRF).

Asymptomatic participants diagnosed to be infected with P. vivax by RT-qPCR will be treated with chloroquine diphosphate (each tablet contains 150 mg chloroquine base) at a dose of 10 mg/kg on days 0 and 1, followed with 5 mg/kg on day 2 (total 25 mg/kg over 3 days) at about 24 hour intervals. Primaquine dosing will also commence on day 0 with chloroquine at a dose of 0.25 mg/kg daily for 14 days (each tablet contains 7.5 mg of primaquine base). Co-administration of chloroquine and primaquine will be observed and recorded in the participant's CRT over the first three days of dosing with the following 11 days of primaquine daily dosing unsupervised.

Where Plasmodium speciation cannot be determined by RT-qPCR due to very low parasitemia but the asymptomatic malaria patient is RT-qPCR positive a treatment course of 3 days of pyronaridine-artesunate plus a single oral dose of primaquine will be administered as described above for the treatment of falciparum malaria.
Intervention code [1] 320877 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327920 0
Monitor the effectiveness of a 3-day course of pyronaridine-artesunate and a single oral dose of primaquine in treating people with asymptomatic falciparum malaria by day 90 of follow-up.


Timepoint [1] 327920 0
At days 30, 60 and 90 post-first intervention dose finger prick blood samples will be collected from participants for the detection of malaria by blood film microscopy and RT-qPCR analysis.
Primary outcome [2] 327921 0
Monitor the effectiveness of a 3-day course of chloroquine and a 14-day course of primaquine in treating people with asymptomatic vivax malaria by day 90 of follow-up.
Timepoint [2] 327921 0
At days 30, 60 and 90 post-first intervention dose finger prick blood samples will be collected from participants for the detection of malaria by blood film microscopy and RT-qPCR analysis.

Primary outcome [3] 328196 0
When Plasmodium speciation cannot be determined by RT-qPCR, monitor the effectiveness of a 3-day course of pyronaridine-artesunate and a single oral dose of primaquine in treating people with asymptomatic malaria by day 90 of follow-up.
Timepoint [3] 328196 0
At days 30, 60 and 90 post-first intervention dose finger prick blood samples will be collected from participants for the detection of malaria by blood film microscopy and RT-qPCR analysis.
Secondary outcome [1] 397012 0
Determine the prevalence of G6PD deficiency in finger prick blood samples collected from participants by measuring G6PD activity using the CareStart Biosensor.
Timepoint [1] 397012 0
Measurement of G6PD activity normalized to hemoglobin using the CareStart Biosensor at Day 0 (before drug treatment)
Secondary outcome [2] 397013 0
Determine whether parasite hemozoin (i.e. malaria pigment) can be detected in people who are infected with asymptomatic malaria using the point-of-care Gazelle (Hemex) device.
Timepoint [2] 397013 0
In people diagnosed to being infected with asymptomatic malaria by RT-qPCR test their finger prick blood samples at Day 0 (before drug treatment) for hemozoin (i.e. malaria pigment) using the Gazelle (Hemex) device.

Eligibility
Key inclusion criteria
• Gender: Males and females;
• Children (5 to <18 years old) and adults;
• People without malaria symptoms such as fever, chills, headache and tiredness;
• Working or residing at and near the study communes, including forested areas near the communes;
• Able to provide information and capillary finger prick blood samples;
• Written informed consent given to participate in the study by the adult or in case of children up to <18 years old (Assent form for children aged 12 to <18 years old) with parent or guardian permission.
Minimum age
5 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Rapid diagnostic test and blood film microscopy positive for malaria infections;
• Inability to communicate well with the study staff (poor mental development or evidence of psychiatric disorder);
• Pregnant or lactating females;
• Any condition that in the judgment of the IMPE-QN/MIPM doctor would make participation in the study unsafe for the potential participant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Because there is no published data on the prevalence of asymptomatic malaria in both Gia Lai and Phu Yen provinces, we assume the prevalence could be between 5% and 15%, based on other studies in Vietnam [Imwong M, Nguyen TN, Tripura R, et al. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015;14:381]. Based on communal health station historical records of where symptomatic malaria patients lived or worked during the malaria seasons of 2018 to 2020, 400 asymptomatic people living in high risk areas (i.e. forest fringe and forest areas) across the four study field sites will be invited to participate in this focal case surveillance for the detection of asymptomatic malaria A further 800 asymptomatic people who live/work at or near symptomatic malaria patients recruited in another study of ours (VDCP01) will be screened at the same field sites during the 2021 malaria season for asymptomatic malaria. Applying a prevalence rate of 5% asymptomatic malaria infections, we plan to treat a total of up to 60 asymptomatic malaria patients from 1,200 screened subjects.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 23791 0
Viet Nam
State/province [1] 23791 0
Gia Lai Province and Phu Yen Province

Funding & Sponsors
Funding source category [1] 308885 0
Government body
Name [1] 308885 0
Australian Defence Force Malaria and Infectious Disease Institute
Address [1] 308885 0
Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Brisbane, QLD 4051
Country [1] 308885 0
Australia
Primary sponsor type
Government body
Name
Australian Defence Force Malaria and Infectious Disease Institute
Address
Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Brisbane, QLD 4051
Country
Australia
Secondary sponsor category [1] 309811 0
None
Name [1] 309811 0
Address [1] 309811 0
Country [1] 309811 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308789 0
Institute of Malariology, Parasitology and Entomology (IMPE) Quy Nhon (IMPE-QN) Institutional Review Board (IMPE-QN-IRB)
Ethics committee address [1] 308789 0
611B Nguyen Thai Hoc Street, Quy Nhon City, Binh Dinh, 10000 Vietnam
Ethics committee country [1] 308789 0
Viet Nam
Date submitted for ethics approval [1] 308789 0
22/04/2021
Approval date [1] 308789 0
29/04/2021
Ethics approval number [1] 308789 0
279/VSR-QLKH

Summary
Brief summary
This primary aim of this study is to detect and treat people who have asymptomatic malaria in four communes in two provinces of central Vietnam during the malaria season of 2021. People with RT-qPCR positive finger prick blood samples for malaria infections will be treated with first-line antimalarial treatment drugs. Initially, 400 asymptomatic people (i.e. without symptoms of malaria such as fever, headaches, nausea and fatigue) will be screened in high malaria risk areas (forest fringes and forested areas) based on previous communal health station historical records (2018-2020) of where symptomatic malaria patients lived or worked. Another 800 asymptomatic people who live and work near symptomatic malaria patients that are treated during the malaria season of 2021 at the same field sites under the concurrently runned VDCP01 study (Therapeutic efficacy surveillance of malaria treatment and drug resistance monitoring in Gia Lai and Phu Yen provinces of Central Vietnam) will also be screened for asymptomatic malaria. We aim to treat up to 60 patients (1,200 x 5% estimated prevalence rate) with asymptomatic malaria with a follow-up period of three months (Days 30, 60 and 90 post commencement of treatment) to determine the efficacy of the drugs. The secondary aims are to determine the prevalence of G6PD deficiency in the study population for the future use of tafenoquine for the elimination of vivax malaria and the potential of the Gazelle (Hemex) device to detect the presence of parasite hemozoin in people with asymptomatic malaria as a point-of-care diagnostic tool.The findings will inform on treatment response of people with asymptomatic malaria to assist in developing new strategies for malaria elimination.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111890 0
Dr Huynh Hong Quang
Address 111890 0
Institute of Malariology, Parasitology and Entomology, Quy Nhon (IMPE-QN)
611B Nguyen Thai Hoc street, Quy Nhon city, Binh Dinh, 10000, Vietnam
Country 111890 0
Viet Nam
Phone 111890 0
+84 905103496
Fax 111890 0
Email 111890 0
huynhquangimpe@yahoo.com
Contact person for public queries
Name 111891 0
Dr Huynh Hong Quang
Address 111891 0
Institute of Malariology, Parasitology and Entomology, Quy Nhon (IMPE-QN)
611B Nguyen Thai Hoc street, Quy Nhon city, Binh Dinh, 10000, Vietnam
Country 111891 0
Viet Nam
Phone 111891 0
+84 905103496
Fax 111891 0
Email 111891 0
huynhquangimpe@yahoo.com
Contact person for scientific queries
Name 111892 0
Dr Michael Douglas Edstein
Address 111892 0
Australian Defence Force Malaria Infectious Disease Institute (ADFMIDI)
Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Brisbane, QLD 4051
Country 111892 0
Australia
Phone 111892 0
+61 403321689
Fax 111892 0
Email 111892 0
mike.edstein@defence.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 12124 0
Study protocol
Citation [1] 12124 0
Link [1] 12124 0
Email [1] 12124 0
Other [1] 12124 0
Type [2] 12125 0
Informed consent form
Citation [2] 12125 0
Link [2] 12125 0
Email [2] 12125 0
Other [2] 12125 0
Type [3] 12126 0
Ethical approval
Citation [3] 12126 0
Link [3] 12126 0
Email [3] 12126 0
Other [3] 12126 0
Summary results
No Results