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Trial registered on ANZCTR


Registration number
ACTRN12622000353796
Ethics application status
Approved
Date submitted
4/11/2021
Date registered
28/02/2022
Date last updated
22/04/2024
Date data sharing statement initially provided
28/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of a multi-component intervention program on the burden of intestinal worms and liver fluke in the Lower Mekong Basin
Scientific title
A Cluster Randomised Controlled Trial to investigate the effect of a multi-component intervention program (human and animal chemotherapy, school and community health and hygiene promotion and active surveillance) on the burden of soil-transmitted helminths and Opisthorchis viverrini in the Lower Mekong Basin
Secondary ID [1] 304860 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
soil-transmitted helminth infection

 322960 0
Opisthorchis viverrini infection 322964 0
Condition category
Condition code
Public Health 320540 320540 0 0
Health promotion/education
Public Health 320541 320541 0 0
Epidemiology
Infection 322015 322015 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Our intervention will include the following components:

1. Chemotherapy: chemotherapy will be administered for soil-transmitted helminths (STH) and opisthorchis viverrini (OV) to animals (cats and dogs) and humans. Praziquantel (40mg/kg oral tablet single dose) will be administered to treat OV, and Albendazole 400mg (oral tablet single dose) will be administered to treat STH infections in humans. Animals will receive praziquantel 40mg/kg to treat OV and pyrantel 10mg/kg to treat STH infections. These medications will be delivered on the spot by health workers. Those who refuse the drug treatment will be recorded. Cats and dogs in intervention villages will be treated with pyrantel and praziquantel at baseline (after stool samples are collected), and 6 months after baseline. Cats and dogs in control villages will be treated after the completion of the study (i.e. 12 months after baseline).

2. School health promotion: the school health promotion will consist of the "Magic Glasses", an educational cartoon that has successfully improved water, sanitation and hygiene (WASH) practices in previous studies.
The Magic Glasses cartoon will be adapted to the Lower Mekong Basin (LMB) following Knowledge, Attitudes and Practices (KAP) surveys with local schoolchildren in the region and/or a literature review of KAP and risk factors associated with OV and STH in the LMB region. Magic Glasses will include information on the transmission of OV and STH, and prevention strategies.

3. Community intervention: the community intervention will largely be based around the distribution of information regarding transmission dynamics, risk factors and prevention methods for STH and OV in community. The main format for this health education will be participatory community meetings led by research team members, and local ‘village health volunteers’ (VHVs). These community meetings will incorporate interactive discussions around STH and OV between research staff, VHVs and community. As well as these community meetings, brochures will be distributed to all village households addressing STH, OV. These brochures will be distributed by the VHVs who also communicate more information to householders at the same time. VHVs are the key health promotion actors at the village level. In our intervention villages these volunteers will be provided with a one-day training program addressing STH and liver fluke transmission and prevention of infection. They will also gain skills communicating this information to the community.

4. Active surveillance: active surveillance of fish, human, cat, and dog stool samples. We will use the modified formalin-ether concentration technique (mFECT) for human and animal stool examination, which our experienced teams have applied extensively for the assessment of OV and STH infection rates and intensities.

Human stool samples (one sample per person) will be collected at baseline, prior to chemotherapy being administered. Follow-up stool samples will be collected one-year after the baseline collection (approximately 12 months after chemotherapy).
Stool samples will be collected from cats and dogs at baseline, 6 months (Cambodia only), and 12 months. Stool samples will be analysed using mFECT. Quality control will be carried out by independent microscopists on 20% of slides mFECT. Fish collected in rivers, ponds/lakes and dams in proximity to study sites will be identified, counted, weighed, and digested using pepsin-HCl, and then examined for OV by a compression/sedimentation method, and metacercariae identified under a stereomicroscope.
Intervention code [1] 321250 0
Treatment: Drugs
Intervention code [2] 321252 0
Behaviour
Intervention code [3] 322343 0
Prevention
Comparator / control treatment
The control group will receive preventive chemotherapy only. This will entail Praziquantel (40mg/kg oral tablet single dose) and albendazole 400mg (oral tablet single dose) for opisthorchis viverrini (OV) and soil-transmitted helminths (STH), respectively.
Control group
Active

Outcomes
Primary outcome [1] 328367 0
OV Infection rate - We will use the modified formalin-ether concentration technique for stool sample examination to measure incidence of OV infection. Positive infection will be defined as the presence of >0 eggs in the stool.
Timepoint [1] 328367 0
One year post-intervention commencement.
Primary outcome [2] 330375 0
STH infection rate - We will use the modified formalin-ether concentration technique for stool sample examination to measure incidence of STH infection. Positive infection will be defined as the presence of >0 eggs in the stool.
Timepoint [2] 330375 0
One year post-intervention commencement.
Primary outcome [3] 330376 0
Infection rate of any helminth infection - We will use the modified formalin-ether concentration technique for stool sample examination to measure incidence of any helminth infection. Positive infection will be defined as the presence of >0 eggs in the stool.
Timepoint [3] 330376 0
One year post-intervention commencement.
Secondary outcome [1] 398819 0
WASH knowledge. Knowledge will be measured by a questionnaire that was developed by the research team and utilised in four previous RCTs assessing STH. We will pilot the questionnaire in each country to ensure applicability.
Timepoint [1] 398819 0
One year post-intervention commencement
Secondary outcome [2] 405993 0
WASH attitudes. Attitudes will be measured by a questionnaire that was developed by the research team and utilised in four previous RCTs assessing STH. We will pilot the questionnaire in each country to ensure applicability.
Timepoint [2] 405993 0
One year post-intervention commencement
Secondary outcome [3] 405994 0
WASH practices. Practices will be measured by a questionnaire that was developed by the research team and utilised in four previous RCTs assessing STH. We will pilot the questionnaire in each country to ensure applicability
Timepoint [3] 405994 0
One year post-intervention commencement
Secondary outcome [4] 405995 0
Intensity of Ascaris lumbricoides infection - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [4] 405995 0
One year post-intervention commencement
Secondary outcome [5] 405996 0
Intensity of hookworm infection - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [5] 405996 0
One year post-intervention commencement
Secondary outcome [6] 405997 0
Intensity of Trichuris trichiura infection - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [6] 405997 0
One year post-intervention commencement
Secondary outcome [7] 405998 0
Intensity of Opisthorchis viverrini infection - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [7] 405998 0
One year post-intervention commencement
Secondary outcome [8] 406703 0
Intensity of Ascaris lumbricoides infection in Cambodia - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [8] 406703 0
One year post-intervention commencement
Secondary outcome [9] 406704 0
Intensity of Ascaris lumbricoides infection in Lao PDR - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [9] 406704 0
One year post-intervention commencement
Secondary outcome [10] 406705 0
Intensity of Ascaris lumbricoides infection in Thailand - We will use the the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [10] 406705 0
One year post-intervention commencement
Secondary outcome [11] 406706 0
Intensity of hookworm infection in Cambodia - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [11] 406706 0
One year post-intervention commencement
Secondary outcome [12] 406707 0
Intensity of hookworm infection in Lao PDR - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [12] 406707 0
One year post-intervention commencement
Secondary outcome [13] 406708 0
Intensity of hookworm infection in Thailand - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [13] 406708 0
One year post-intervention commencement
Secondary outcome [14] 406709 0
Intensity of Trichuris trichiura infection in Cambodia - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [14] 406709 0
One year post-intervention commencement
Secondary outcome [15] 406710 0
Intensity of Trichuris trichiura infection in Lao PDR - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [15] 406710 0
One year post-intervention commencement
Secondary outcome [16] 406711 0
Intensity of Trichuris trichiura infection in Thailand - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [16] 406711 0
One year post-intervention commencement
Secondary outcome [17] 406712 0
Intensity of Opisthorchis viverrini infection in Cambodia - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [17] 406712 0
One year post-intervention commencement
Secondary outcome [18] 406713 0
Intensity of Opisthorchis viverrini infection in Lao PDR - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [18] 406713 0
One year post-intervention commencement
Secondary outcome [19] 406714 0
Intensity of Opisthorchis viverrini infection in Thailand - We will use the modified formalin-ether concentration technique for stool sample examination, intensity will be measured by egg count.
Timepoint [19] 406714 0
One year post-intervention commencement

Eligibility
Key inclusion criteria
a) resident of the village selected for the study,
b) resident of the village for >12 months,
c) 5-75 years of age,
d) do not intend to migrate in the next year,
e) will continuously reside in the study area over the study period,
f) the resident has given informed consent,
g) resident minors have the informed consent of their parent/guardian.
Minimum age
5 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
none

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
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
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
For the main trial, sample sizes will be calculated assuming a design effect of 4 (determined from regional STH data) an alpha of 0.05 and power of >80%; this yielded a necessary sample size of N=4800 at the end of the trial to detect as low as a 30% combined efficacy of Lawa model + Magic Glasses. Assuming an incidence rate of at least 25% in the non-intervention group, we will recruit a sentinel cohort of N=6000 across 6 village pairs (N=500/village) to account for 20% attrition.

Preliminary analysis will calculate human prevalence of infection and intensity in those infected for each time-point and each village, with 95% confidence intervals. Exposure-related variables (age, sex, occupation, e.g.) will be examined across villages. Multivariate regression (covariates will include baseline infection, relevant others selected from preliminary analyses) will be used for formal analyses of follow-up incidence (log-binomial model) and intensity of infection (log-negative binomial model). A multi-level model, stratified by country and with village as a random effect will be applied using SAS software (SAS Institute, Cary, NC). Relative risk estimates will be converted to estimates of control program effectiveness against incident infection.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/04/2022
Actual
22/05/2023
Date of last participant enrolment
Anticipated
1/04/2023
Actual
21/12/2023
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
6000
Accrual to date
Final
6200
Recruitment outside Australia
Country [1] 24003 0
Thailand
State/province [1] 24003 0
Country [2] 24004 0
Lao People's Democratic Republic
State/province [2] 24004 0
Country [3] 24005 0
Cambodia
State/province [3] 24005 0

Funding & Sponsors
Funding source category [1] 309233 0
Government body
Name [1] 309233 0
National Health and Medical Research Council
Country [1] 309233 0
Australia
Primary sponsor type
Individual
Name
Professor Darren Gray
Address
Research School of Population Health M Block Extension (Building 62A)
62 Mills Rd
Australian National University
Acton
ACT 2601
Country
Australia
Secondary sponsor category [1] 310217 0
None
Name [1] 310217 0
Address [1] 310217 0
Country [1] 310217 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309080 0
Australian National University Human Research Ethics Committee
Ethics committee address [1] 309080 0
Ethics committee country [1] 309080 0
Australia
Date submitted for ethics approval [1] 309080 0
08/12/2021
Approval date [1] 309080 0
17/08/2022
Ethics approval number [1] 309080 0
Ethics committee name [2] 315172 0
Ministry of Health National Ethics Committee for Health Research
Ethics committee address [2] 315172 0
Ethics committee country [2] 315172 0
Cambodia
Date submitted for ethics approval [2] 315172 0
29/05/2023
Approval date [2] 315172 0
27/06/2023
Ethics approval number [2] 315172 0
197
Ethics committee name [3] 315173 0
Ministry of Health National Ethics Committee for Health Research
Ethics committee address [3] 315173 0
Ethics committee country [3] 315173 0
Lao People's Democratic Republic
Date submitted for ethics approval [3] 315173 0
01/12/2022
Approval date [3] 315173 0
22/12/2022
Ethics approval number [3] 315173 0
111
Ethics committee name [4] 315174 0
Institutional Animal Care and Use Committee of Khon Kaen University
Ethics committee address [4] 315174 0
Ethics committee country [4] 315174 0
Thailand
Date submitted for ethics approval [4] 315174 0
01/04/2022
Approval date [4] 315174 0
21/04/2022
Ethics approval number [4] 315174 0
660201.2.11/245 (39)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112906 0
Prof Darren Gray
Address 112906 0
QIMR Berghofer - Global Health & Tropical Medicine
300 Herston Road,
Herston, Queensland 4006
Country 112906 0
Australia
Phone 112906 0
+61 7 3362 0247
Fax 112906 0
Email 112906 0
darren.gray@qimrberghofer.edu.au
Contact person for public queries
Name 112907 0
Darren Gray
Address 112907 0
QIMR Berghofer - Global Health & Tropical Medicine
300 Herston Road,
Herston, Queensland 4006
Country 112907 0
Australia
Phone 112907 0
+61 7 3362 0222
Fax 112907 0
Email 112907 0
darren.gray@qimrberghofer.edu.au
Contact person for scientific queries
Name 112908 0
Darren Gray
Address 112908 0
QIMR Berghofer - Global Health & Tropical Medicine
300 Herston Road,
Herston, Queensland 4006
Country 112908 0
Australia
Phone 112908 0
+61 7 3362 0222
Fax 112908 0
Email 112908 0
darren.gray@qimrberghofer.edu.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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12658Study protocol  suji.oconnor@anu.edu.au 382462-(Uploaded-03-11-2021-15-20-23)-Study-related document.docx
13948Informed consent form    382462-(Uploaded-03-11-2021-15-27-09)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.