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Trial registered on ANZCTR


Registration number
ACTRN12618000520235
Ethics application status
Approved
Date submitted
23/02/2018
Date registered
9/04/2018
Date last updated
26/02/2020
Date data sharing statement initially provided
15/03/2019
Date results information initially provided
26/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The SToP Trial: See Treat Prevent skin sores and scabies A healthy skin programme in communities in the Kimberley.
Scientific title
The SToP (See, Treat, Prevent) Skin Sores and Scabies Trial: A cluster randomised, stepped-wedge trial for skin disease control in remote Western Australia.
Secondary ID [1] 292833 0
Therapeutic Goods Administration (TGA) Clinical Trials Notification (CTN) Application ID Number: CT-2017-CTN-01788-1 v1
Secondary ID [2] 292926 0
Western Australia Department of Health - FutureHealth WA Third Year Initiative: Kimberley Healthy Skin Program (FHWAYR3-2015/16-KHS)
Secondary ID [3] 292927 0
National Health and Medical Research Council Project Funding (GNT1128950)
Universal Trial Number (UTN)
U1111-1201-7842
Trial acronym
SToP (See Treat Prevent) Trial
Linked study record
NA

Health condition
Health condition(s) or problem(s) studied:
impetigo 304673 0
scabies 304674 0
crusted scabies 304675 0
Condition category
Condition code
Infection 303988 303988 0 0
Other infectious diseases
Skin 304101 304101 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The overall duration of the trial is four years and it will be conducted in four Kimberley community clusters using a stepped-wedge design. The stepped-wedge design allows the scientific rigour of a randomized trial, whilst acknowledging the pragmatic need to gradually roll out an intervention over several communities in a remote region. The trial comprises of four phases:
1. Baseline
2. Intervention (implementation of the "SToP activities", where clusters are randomly "stepped" onto the SToP activities, following the stepped wedge design; two clusters randomised to the SToP activities known as "step 1" and two clusters randomised to the SToP activities one year later known as "step 2").
3. Follow up.
4 Maintenance.

Intervention: The "SToP Activities"
There are three intervention components, collectively known as the “SToP activities”. As per the stepped-wedge design, all community clusters will have transitioned ("stepped" onto) to the SToP activities upon completion of the trial. In Step 1, two randomly selected community clusters will receive the SToP activities. In Step 2, the remaining 2 community clusters will transition to receive the SToP activities. The SToP activities have three main components - (a)"See"ing, (b)"Treat"ing, and (c) "Prevent"ing skin infections:

a) “See”ing skin infections by providing health care worker training on the diagnosis and treatment of skin infections, and by conducting school-based surveillance for skin infections.

Health care worker training will be provided by trial staff and include face-to-face training sessions to up-skill health care workers with the latest evidence based recommendations for identifying and treating skin infections. Health care workers will be invited to attend this training session prior to each school based surveillance/screening visit (described below). The training session duration will range from 1-2hours up to a full day (depending on availability of health care workers). Health care workers will also be provided with online and paper resources of this training information, such as a training flipchart, self-assessment quiz for feedback on their learning, and training videos. Where possible, trial staff will provide further 'hands on' training and demonstrate identifying skin infections by partnering with health care worker staff to complete the school-based surveillance/screening.

The school-based surveillance/screening (and early childhood where feasible) will involve trial staff (and where possible, health care worker staff) screening children at school to assess their skin for infections. If skin infections are identified, the child will be referred to the local clinic for treatment. Their parent/caregiver will also be notified and recommended to take them to the clinic for treatment. School surveillance/screening visits will occur in all 4 communities three times per year for 3 years (total of 9 visits).

b) “Treat”ing skin infections according to the latest evidence and utilising ‘Structured Administration and Supply Arrangements’ (previously known as “standing orders”) for streamlined treatment, namely co-trimoxazole twice daily for 3 days for impetigo, ivermectin on days 0 and 8 for scabies cases and their contacts and holistic care including treatment of those identified with crusted scabies (ivermectin on days 0, 1 and 8 for grade 1 crusted scabies). Treatment will occur at the local community clinic and occur as individuals present to the clinic and are assessed as requiring this treatment.

Mode, dose and duration for cotrimoxazole (for treatment of impetigo): 4mg/kg/dose twice daily for 3 days according to weight band based dosing of the trimethoprim component of trimethoprim/ sulphamethoxazole. Either syrup or tablets will be recommended depending on age and preference. Adherence to the treatment will not be monitored.

The investigational medicinal product (IMP) for this trial is ivermectin (for treatment of scabies/crusted scabies). This trial will use ivermectin off label as first line treatment for cases of scabies, preventative treatment of asymptomatic household contacts of the diagnosed cases, and be administered to patients more than 15kg but irrespective of age. Mode, dose and duration for ivermectin: 200 µg/kg (weight band dosing) single dose oral tablet (once daily), taken on day 0 and day 8. Ivermectin dosing will predominantly occur at the clinic as it will be a single dose on day 0 (and day 8) if indicated. Adherence to the treatment will not be monitored but adverse events will be recorded.

Patients presenting with both scabies and impetigo will be treated for both conditions simultaneously as described above.

c) “Prevent”ing skin infections through embedded, culturally informed and developed health promotion and environmental health activities. These activities will occur throughout the trial at a community level and as determined by local health promotion and environmental health services. Health promotion and environmental health activities are part of routine care in the Kimberley. As such, the service partners in the research will continue to deliver health promotion/environmental health as per usual activities. The duration and frequency will vary depending on need and prioritisation from the service providers. The trial team will collect data on how frequently this occurs for the overall evaluation of the trial.

The overall duration of the study is four years.
Intervention code [1] 299155 0
Early detection / Screening
Intervention code [2] 299156 0
Treatment: Drugs
Intervention code [3] 299157 0
Prevention
Comparator / control treatment
Each cluster acts as its own control and will be compared pre/post SToP activities for within-cluster analyses. Control treatment during the baseline period and Step 1 for the clusters/arm not yet receiving the SToP activities (intervention) will be standard of care in each of the communities at the time of the study. Standard of care is as per the Kimberley guidelines.
Control group
Active

Outcomes
Primary outcome [1] 303429 0
Diagnosis of impetigo at school screening in children aged 5 and less than 10 years of age.

As assessed by physical skin examination at school screening surveillance visits.
Timepoint [1] 303429 0
Assessed at 9 time points: 3 times per year for 3 years (total of 9 visits). Due to the need to operationalise the surveillance in the school setting and in a very remote location impacted by flooding during the Wet Season (Nov – Feb), the surveillance visits will occur within the school terms and will be three times per year. It is not possible to give a more defined interval than this.
Secondary outcome [1] 338894 0
Diagnosis of scabies in children aged between 5 and less than 10 years.

As assessed by physical skin examination at school screening surveillance visits.
Timepoint [1] 338894 0
Assessed at 9 time points: 3 times per year for 3 years (total of 9 visits). Due to the need to operationalise the surveillance in the school setting and in a very remote location impacted by flooding during the Wet Season (Nov – Feb), the surveillance visits will occur within the school terms and will be three times per year. It is not possible to give a more defined interval than this.
Secondary outcome [2] 338895 0
The diagnosis of impetigo at early childhood centres and the clinic in children aged 0 – 4 years.

As assessed by physical skin examination at school screening surveillance visits; which will also include early childhood centre screening where feasible.
Timepoint [2] 338895 0
Assessed at 9 time points: 3 times per year for 3 years (total of 9 visits). Due to the need to operationalise the surveillance in the school setting and in a very remote location impacted by flooding during the Wet Season (Nov – Feb), the surveillance visits will occur within the school terms and will be three times per year. It is not possible to give a more defined interval than this.
Secondary outcome [3] 338896 0
The diagnosis of scabies at early childhood centres and the clinic in children aged 0 – 4 years.

As assessed by physical skin examination at school screening surveillance visits; which will also include early childhood centre screening where feasible.
Timepoint [3] 338896 0
Assessed at 9 time points: 3 times per year for 3 years (total of 9 visits). Due to the need to operationalise the surveillance in the school setting and in a very remote location impacted by flooding during the Wet Season (Nov – Feb), the surveillance visits will occur within the school terms and will be three times per year. It is not possible to give a more defined interval than this.
Secondary outcome [4] 338897 0
Awareness of skin health in interviews among community members and health staff.

Assessed as per study interview guide.
Timepoint [4] 338897 0
Completed at Baseline, 12 months post commencement of intervention (End of Step 1) and 24 months post commencement of intervention (End of Step 2).
Secondary outcome [5] 338898 0
Overall acceptability of the program measured at baseline and follow up.

Assessed as per study interview guide.
Timepoint [5] 338898 0
Completed at Baseline, 12 months post commencement of intervention (End of Step 1) and 24 months post commencement of intervention (End of Step 2).
Secondary outcome [6] 338899 0
Overall clinic presentations due to skin conditions including abscess in all age-deciles.

Assessed by clinic medical records.
Timepoint [6] 338899 0
This data will be captured monthly for 3 years but will be reported annually for 3 years.
Secondary outcome [7] 338900 0
Monitoring age at first scabies and impetigo diagnosis in the 12-month birth cohort after the SToP activities have been adopted.

Assessed by clinic medical records.
Timepoint [7] 338900 0
This data will be captured once-off, 24 months post commencement of intervention (End of Step 2).
Secondary outcome [8] 338901 0
All-cause clinic presentations and hospitalisations from the communities, (including those for non-skin eg anaemia, skin related eg sepsis, and skin causes) in children aged <10 years.

Assessed by clinic medical records.
Timepoint [8] 338901 0
This data will be captured monthly for 3 years but will be reported annually for 3 years.
Secondary outcome [9] 344486 0
Monitoring of cotrimoxazole resistance in circulating S. aureus and GAS strains.

To understand the circulating clones of S. aureus and GAS and resistance phenotype/ genotype, each child with a crusted or purulent skin sore diagnosed during school screening will have a bacterial culture swab collected using previously published methods for transportation and susceptibility testing. In addition, each child participating in the early childhood and school surveillance programs will have a throat swab collected at baseline and end of step 2 for detection of S. aureus and S. pyogenes.

Each swab will be processed for detection of Staphylococcus aureus and Streptococcus pyogenes on HBA, HBA+CNA and MRSA Chromagar. Routine susceptibility testing will be performed for S. aureus and S. pyogenes. In addition, an E test (Biomerieux) for GAS and S. aureus susceptibility to trimethoprim and cotrimoxazole will also be performed on MHA or MHF as per EUCAST methods.

Cultures will be examined for morphologic growth of beta-haemolytic streptococci (BHS; off white colonies) and S. aureus (white or yellow, ß-haemolytic). Colonies of BHS will be subcultured onto HBA plates for subsequent identification using a Streptococcal Grouping Kit (Cat# DR0585, Oxoid). Isolates of group A, C and G will be identified and stored frozen in STGGB. A scraping of the stored frozen culture will be used to subculture the isolate for antibiotic susceptibility testing. Both a disc diffusion (penicillin, erythromycin and clindamycin) and E test (trimethoprim and trimethoprim-sulphamethoxazole) will be used to determine susceptibility of BHS to these antibiotics. Colonies resembling staphylococci will be subcultured and identified using a rapid latex agglutination test (Staphytect Plus; Cat# DR0850, Oxoid). S. aureus isolates will be stored frozen in STGGB. A scraping of the stored frozen culture will be used to subculture the isolate for antibiotic susceptibility testing.

Whole Genome Sequencing (WGS) will be performed on skin and throat isolates collected at baseline and end of step 2 to assess for genotypic resistance, clonality and virulence factors.

We will also monitor routinely collected microbiology data e.g. antibiograms from appropriate surrogate markers to observe the ecological impact of increased use of cotrimoxazole.
Timepoint [9] 344486 0
Annually for 3 years.
Secondary outcome [10] 344487 0
Monitoring of antimicrobial prescribing for skin infections and other conditions.

Collected monthly via data extractions from clinic medical records. The monthly data extractions will report on medications administered/supplied, and according to what condition (including skin infections or other).
Timepoint [10] 344487 0
This data will be collected monthly for 3 years but reported annually for 3 years.
Secondary outcome [11] 344488 0
Determine the cost of diagnosing and managing skin infections, and the cost of the routine SToP activities.

Data will be collected retrospectively from study records and documentation pertaining to the costs that were expended to complete skin infection diagnosis, skin infection management, and implementation of the SToP activities.
Timepoint [11] 344488 0
At the conclusion of the trial.

Eligibility
Key inclusion criteria
Cluster inclusion criteria
-Remote Aboriginal community cluster in the Kimberley region of Western Australia
-Community cluster population is around 1,000 people
-Community cluster has access to a clinic staffed full time by nurses
-Community cluster is practically accessible to research staff
-Community cluster indicate interest and consent to participate in trial
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-Community elects not to participate in the trial during consultation phase

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The community cluster is the unit of randomisation. Allocation involves contacting the holder of the allocation schedule who was “off-site” or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Cluster randomised trial with stepped wedge design.
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample Size:
This cluster randomised trial (CRT) uses a stepped-wedge design with 2 steps and 2 measurements during baseline and each step. Assuming baseline prevalence of impetigo to be 40% or higher, we will have at least 90% power to detect a 50% reduction in impetigo prevalence in school children aged 5-9 years in 4 large communities. This assumes: (1) 2 communities (clusters) switch to SToP activities at each step; (2) an average cluster size of 84 children aged 5-9 years in each community, based on communities with at least 1,000 people with approximately 12% aged between 5-9 years and a daily school attendance rate of around 70%; (3) a significance level of 5%; (4) an intra-cluster correlation (ICC) of 0.05 (since the ICC is unknown we chose a value that maximises the design effect and thus the sample size, i.e. assumes the worst case); and (5) absence of cluster by time interactions and similar time trends across all clusters.

Analysis and statistical methods for primary endpoint:
Generalised linear mixed-effects regression (GLMM) will be used to estimate the odds ratio of impetigo in the intervention period compared to the control period, adjusting for secular trends (time) and grouping community.

Analysis and statistical methods for secondary endpoints:
GLMM and descriptive statistics will be used to analyse the secondary quantitative outcomes. Qualitative outcomes will be be coded as part of a thematic analysis.

Recruitment
Recruitment status
Active, not 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 in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 297464 0
Government body
Name [1] 297464 0
Government of Western Australia, Department of Health
Address [1] 297464 0
Research Development Unit
Department of Health
PO Box 8172
Perth Business Centre
Perth WA 6849
Country [1] 297464 0
Australia
Funding source category [2] 297553 0
Government body
Name [2] 297553 0
National Health and Medical Research Council (NHMRC)
Address [2] 297553 0
Research Committee Secretariat NHMRC
GPO Box 1421
Canberra ACT 2601
Country [2] 297553 0
Australia
Funding source category [3] 305084 0
Government body
Name [3] 305084 0
Healthway
Address [3] 305084 0
38 Station St, Subiaco WA 6008
Country [3] 305084 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Telethon Kids Institute
Address
100 Roberts Road
Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 296563 0
None
Name [1] 296563 0
Address [1] 296563 0
Country [1] 296563 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298570 0
Western Australia Aboriginal Health Ethics Committee (WAAHEC)
Ethics committee address [1] 298570 0
450 Beaufort Street
Highgate
Western Australia
6003
Ethics committee country [1] 298570 0
Australia
Date submitted for ethics approval [1] 298570 0
15/09/2017
Approval date [1] 298570 0
04/12/2017
Ethics approval number [1] 298570 0
819
Ethics committee name [2] 298649 0
Child and Adolescent Health Service (CAHS) Human Research Ethics Committee (HREC)
Ethics committee address [2] 298649 0
GPO Box D184, Perth
Western Australia 6840
Ethics committee country [2] 298649 0
Australia
Date submitted for ethics approval [2] 298649 0
19/09/2017
Approval date [2] 298649 0
02/11/2017
Ethics approval number [2] 298649 0
RGS0000000584
Ethics committee name [3] 299455 0
University of Western Australia Human Research Ethics Committee
Ethics committee address [3] 299455 0
The University of Western Australia
M459, 35 Stirling Highway
Crawley WA 6009 Australia
Ethics committee country [3] 299455 0
Australia
Date submitted for ethics approval [3] 299455 0
16/11/2017
Approval date [3] 299455 0
20/11/2017
Ethics approval number [3] 299455 0
RA4204123

Summary
Brief summary
What is the problem?
Skin infections (sores and scabies) are common in Aboriginal communities. At any one time, almost one out of every two children have skin sores, and one in five children may have scabies. If skin sores are not treated, they can lead to serious illness including severe infection (sepsis), bone disease, kidney disease and possibly rheumatic heart disease. Skin infections are potentially one of the most treatable causes of serious disease in Aboriginal communities.

Why are so many children affected?
There are many reasons for this. One of these may be that as skin sores are very common, they can become “normalised”, which might mean the child doesn’t complain, they don’t go to clinic, or the doctor or health worker doesn’t treat the sores because “everyone has them”.

What we want to do - the SToP Trial
Skin health has been identified as one of the health priorities by communities and health services in the Kimberley. A number of healthy skin activities are currently underway. The SToP trial study aims to strengthen and build on these existing practices to improve the
awareness, detection, and treatment of skin infections in the Kimberley. The SToP trial study will implement several activities aimed at Seeing (S), Treating (T) and Preventing (P) skin infections:

Seeing: Provide health worker training to improve detection and treatment of skin infections, and introduce a school-based screening program to check kids’ skin for
skin infections, and refer them to their local clinic if they need treatment.

Treating: At the local community clinic, provide streamlined treatment medications for skin infections that are safe, effective, less invasive and easier for people to manage.
Specifically, Cotrimoxazole (oral syrup or pill medication that you swallow) will be used to treat skin sores rather than an injection of Benzathine Penicillin, which can be painful. Ivermectin (oral pill medication that you swallow) will be used to treat scabies rather than Permethrin medication (an oily cream that needs to be applied to the whole body, which can be messy and may come off).

Preventing: We will work with local communities and health services to strengthen culturally appropriate health promotion activities about healthy skin and stopping skin
infections. This will increase community awareness about what skin infections (sores and scabies) are, why they are important and why getting treatment is important. We will
also work with communities and health services to strengthen the role of environmental health activities in helping to manage skin infections. This will increase community awareness about the importance of environmental health in relation to skin health, and to help ensure community members have access to environmental health services.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77506 0
Dr Asha Bowen
Address 77506 0
Telethon Kids Institute
100 Roberts Road
Subiaco WA 6008
Country 77506 0
Australia
Phone 77506 0
+61 (08) 9340 7993
Fax 77506 0
Email 77506 0
asha.bowen@telethonkids.org.au
Contact person for public queries
Name 77507 0
Dr Asha Bowen
Address 77507 0
Telethon Kids Institute
100 Roberts Road
Subiaco WA 6008
Country 77507 0
Australia
Phone 77507 0
+61 (08) 9340 7993
Fax 77507 0
Email 77507 0
asha.bowen@telethonkids.org.au
Contact person for scientific queries
Name 77508 0
Dr Asha Bowen
Address 77508 0
Telethon Kids Institute
100 Roberts Road
Subiaco WA 6008
Country 77508 0
Australia
Phone 77508 0
+61 (08) 9340 7993
Fax 77508 0
Email 77508 0
asha.bowen@telethonkids.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not appropriate to share data from these remote Aboriginal communities without consultation and consent.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary