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Trial registered on ANZCTR


Registration number
ACTRN12619001712190p
Ethics application status
Submitted, not yet approved
Date submitted
28/11/2019
Date registered
5/12/2019
Date last updated
5/12/2019
Date data sharing statement initially provided
5/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A trial of community wide treatment to reduce scabies in a village setting in northern India
Scientific title
A trial of ivermectin-based mass drug administration (MDA) for scabies in northern India
Secondary ID [1] 299925 0
Nil known
Universal Trial Number (UTN)
U1111-1244-6032
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Scabies
315355 0
Condition category
Condition code
Skin 313663 313663 0 0
Dermatological conditions
Infection 313742 313742 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an ivermectin-based mass drug administration program
The entire population of the study region will be offered treatment with either oral ivermectin or topical permethrin (where there are contraindications to ivermectin). Two doses of the relevant medication will be provided to each participant (one week apart).
Ivermectin Dose Regime (based on weight)
- 15-25kg - 3.0mg
- 26 - 37.5kg - 6.0mg
- 37.6-50kg - 9.0mg
- 51-75kg - 12.0mg
- > 75kg - 15mg
Contraindications to ivermectin include:
- Weight under 15kg
- Pregnancy
- Breastfeeding
- Those who are seriously unwell (Unable to engage in normal activities of daily living without assistance because of illness)
- People who have previously suffered from a serious adverse event thought to be due to a reaction to ivermectin
- People taking warfarin
Anyone meeting these criteria will receive 5% permethrin cream. This will be applied all over the body from neck to toe and washed off after a minimum of 8 hours (after 4 hours for children under the age of 2 months).

For those receiving ivermectin (the majority of the participants), both doses will be given and directly observed by the study team. Those receiving permethrin will apply this at home in the evening (thus not directly observed). However, they will receive follow up at 1 week when the second dose is administered, at which time the team will be able to provide a reminder to use the cream if they have not already.

Skin examinations will be conducted at baseline and then again at 12 months to determine the prevalence of scabies.
Intervention code [1] 316196 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322112 0
Community prevalence of scabies at 12 months compared to baseline. Prevalence will be calculated as the percentage of the total population which is diagnosed with scabies at each time point (baseline and 12 months). The most recent official census data will be used to determine the total population size for this calculation. The prevalence at `12 months will be compared to prevalence at baseline using two-sided chi-squared test with a significance level of 0.05.

The percentage of the population which has scabies will be diagnosed clinically based on a standardised skin examination used by previous MDAs in countries such as Fiji and the Solomon Islands. Cases of scabies are defined using the "Consensus criteria for the diagnosis of scabies" published by Daniel Engleman et al in their 2018 paper of the same name. These skin examinations will be performed on every participant in the study at baseline and 12 months. The entire community will be eligible to participate in this study, and therefore also the skin examination, if they consent.
Timepoint [1] 322112 0
One year after intervention
Secondary outcome [1] 377374 0
Community prevalence of impetigo at 12 months compared to baseline. Prevalence will be calculated as the percentage of the total population (total population determined by official census data) which is diagnosed with impetigo during the community wide skin examinations at baseline and 12 months. The prevalence at `12 months will be compared to prevalence at baseline using two-sided chi-squared test with a significance level of 0.05.

The amount of impetigo in the community will be determined clinically via standardised skin examination based (as for scabies) on protocol used in previous MDAs in Fiji and the Solomon Islands. These skin examinations will be performed on every participant at baseline and 12 months. The entire community will be eligible to participate in this study, and therefore also the skin examination, if they consent.
Timepoint [1] 377374 0
One year after intervention
Secondary outcome [2] 377375 0
Community acceptability of mass drug administration (MDA) protocol assessed via community survey.
The survey used is titled "Acceptability survey for community respondents following the special distribution of Scabies pills". This survey has been previously used in Scabies MDAs in Fiji and the Solomon Islands.
Timepoint [2] 377375 0
One week after initial visit (survey conducted concurrently with administration of second dose of medication)
Secondary outcome [3] 377377 0
Coverage of the MDA (calculated individually for dose 1 and 2).
Measured by the number of doses distributed divided by the total population (from the most recent census data)
Timepoint [3] 377377 0
At baseline (first dose) and one week (second dose)
Secondary outcome [4] 377380 0
Safety (measured by occurrence of self-reported adverse effects)
Potential adverse effects include;
- Ivermectin - fatigue, abdominal pain, anorexia, constipation, diarrhoea, nausea, vomiting, dizziness / vertigo, somnolence, tremor, pruritis, rash, urticaria
The most common of these are dizziness and pruritis, both of which occur in approximately 2.8%, followed by diarrhoea and nausea which each occur is approximately 1.8%.
- Permethrin - stinging, burning or redness of the skin

Adverse effects will be assessed by self-report during the community acceptability survey conducted one week after the initial administration of the medication (at the time of the second dose). The survey is titled "Acceptability survey for community respondents following the special distribution of Scabies pills". This survey has been previously used in Scabies MDAs in Fiji and the Solomon Islands and is the same survey used to assess community acceptability as described above in secondary outcome 2.
The local community health workers (based in each village) will also report and refer any severe adverse events to the local study team.
Timepoint [4] 377380 0
One week post intervention.

Eligibility
Key inclusion criteria
All residents of the study area are eligible to participate in this study
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
As this is a mass drug administration program, all residents of the selected area are eligible for inclusion in this study. However, the exclusion criteria for drug administration are:
- Allergy to any of the components of the allocated drug regimen
- Currently on or has taken ivermectin in the previous 7 days
- Clinical diagnosis of crusted scabies (will be referred for specialist assessment)

These criteria exclude individuals from study drug administration but they remain eligible for inclusion in the study.

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)
Allocation is not concealed (non-randomised trial with only one study arm)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable (no randomisation in this trial)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A baseline prevalence of 8-9% is assumed. This is based on a previous survey in this region, performed in low risk areas in a low scabies prevalence season, which showed a scabies prevalence of 4.4%. Thus, it is expected that in this higher risk area in a high risk season (winter), the prevalence is likely to be around 8-9%. Based on previous research, the overall prevalence would fall to approximately 5% using ivermectin based MDA. Given a population of approximately 2200 in Gram Panchayat, and assuming 80% response rate, 20% loss to follow up, and a 0.35 correlation between paired observations, a sample size of 1400 surveyed participants will allow us to detect the difference in prevalence at 0.05 significance level with a study power well above 90%. Estimated study power was calculated using the Power and Sample Size module of Stata version 14.

Statistical analysis plan:
- Prevalence of scabies and impetigo will be calculated as a percentage of total population. The prevalence at 12 months will be compared to baseline using two-sided chi-squared test with a significance level of 0.05. Change in prevalence will be analysed in terms of absolute difference and relative reductions. To detect changes within participants across the two timepoints, proportions of scabies of discordant pairs (individuals with scabies at baseline but not at 12 months and vice versa) will be calculated.

The overall coverage of each dose, as well as age, group and gender specific coverage will be calculated using as a denominator the population figures from the most recent official administrative data. The community acceptability survey results will also be analysed both at a region level and also by gender, age and village.

The number of self-reported adverse events will be categorised and expressed as a rate and compared to those from previous similar studies.

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] 22150 0
India
State/province [1] 22150 0
Uttarakhand

Funding & Sponsors
Funding source category [1] 304386 0
University
Name [1] 304386 0
The Nossal Institute for Global Health (University of Melbourne)
Address [1] 304386 0
Melbourne School of Population and Global Health,
University of Melbourne
333 Exhibition Street, Melbourne
Victoria, 3004
Country [1] 304386 0
Australia
Funding source category [2] 304405 0
Charities/Societies/Foundations
Name [2] 304405 0
International Dermatology Outreach Program
Address [2] 304405 0
C/O Royal Children's Hospital
48 Flemington Rd, Parkville VIC 3052, Australia
Country [2] 304405 0
Australia
Primary sponsor type
University
Name
The Nossal Institute for Global Health (University of Melbourne)
Address
Melbourne School of Population and Global Health,
University of Melbourne
333 Exhibition Street, Melbourne
Victoria, 3004
Country
Australia
Secondary sponsor category [1] 304639 0
Other Collaborative groups
Name [1] 304639 0
Murdoch Children's Research Institute
Address [1] 304639 0
Royal Children's Hospital
Flemington Road, Parkville Victoria 3052 Australia
Country [1] 304639 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304824 0
The Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 304824 0
Research Ethics & Governance
The Royal Children's Hospital
Level 4, South Building
50 Flemington Road
Parkville Vic 3052
Ethics committee country [1] 304824 0
Australia
Date submitted for ethics approval [1] 304824 0
16/10/2019
Approval date [1] 304824 0
Ethics approval number [1] 304824 0

Summary
Brief summary
This is a trial of a mass drug administration program with ivermectin for community level scabies control in rural north India. This study will be conducted in four villages in the state of Uttarakhand in north India. All residents of the region will be eligible to participate and will be offered two doses of ivermectin seven days apart (or permethrin cream where ivermectin is contraindicated). A skin examination will be performed at baseline and repeated at 12 months.

Similar programs have been shown to be very effective in other countries (e.g. Fiji, Solomon Islands) in reducing the rates of scabies in the community. However, these countries have very high rates of scabies in the community at baseline (much higher than in India). This trial aims to assess whether these programs remain effective in areas with a lower baseline prevalence of scabies (estimated 8-9% compared to > 30%).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98326 0
Dr Daniel Engelman
Address 98326 0
Tropical Disease Group, Murdoch Children's Research Institute
Royal Children's Hospital Melbourne
48 Flemington Road, Parkville, Victoria 3052 Australia
Country 98326 0
Australia
Phone 98326 0
+61 393455522
Fax 98326 0
Email 98326 0
Daniel.Engelman@rch.org.au
Contact person for public queries
Name 98327 0
Dr Daniel Engelman
Address 98327 0
Tropical Disease Group, Murdoch Children's Research Institute
Royal Children's Hospital Melbourne
48 Flemington Road, Parkville, Victoria 3052 Australia
Country 98327 0
Australia
Phone 98327 0
+61 393455522
Fax 98327 0
Email 98327 0
Daniel.Engelman@rch.org.au
Contact person for scientific queries
Name 98328 0
Dr Daniel Engelman
Address 98328 0
Tropical Disease Group, Murdoch Children's Research Institute
Royal Children's Hospital Melbourne
48 Flemington Road, Parkville, Victoria 3052 Australia
Country 98328 0
Australia
Phone 98328 0
+61 393455522
Fax 98328 0
Email 98328 0
Daniel.Engelman@rch.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the de-identified data set collected during the trial
When will data be available (start and end dates)?
Start date - 28th February 2021 (approximately)
No end date determined
Available to whom?
Only researchers who provide a methodologically sound proposal
Available for what types of analyses?
Available only for analyses to achieve the aims in the approved proposal
How or where can data be obtained?
Data access can be arranged subject to approvals by the Principal Investigator (using contact details in ANZCTR form)
What supporting documents are/will be available?
No other documents available
Summary results
No Results