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Trial registered on ANZCTR


Registration number
ACTRN12619001610123
Ethics application status
Approved
Date submitted
11/11/2019
Date registered
21/11/2019
Date last updated
21/11/2019
Date data sharing statement initially provided
21/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring a tea tree oil (TTO)-based skin treatment for tungiasis in children
Scientific title
Treatment of tungiasis using a proprietary tea tree oil (TTO)-gel formulation in children: Protocol for a randomised, controlled, proof-of principle trial
Secondary ID [1] 299731 0
None
Universal Trial Number (UTN)
U1111-1243-2294
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tungiasis (sand flea disease) 315077 0
Condition category
Condition code
Skin 313417 313417 0 0
Dermatological conditions
Infection 313473 313473 0 0
Other infectious diseases
Public Health 313474 313474 0 0
Other public health

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Test group- treatment of tungiasis with a 5% (v/w), proprietary tea tree oil (TTO) gel

The feet of the participants will be washed with water and non-medicated soap, dried with a clean towel, and the participants’ toenails will be clipped to enable easier application of the test medication. Then, the test medication will be applied twice daily on days 1, 4 and 7 by trained study personnel (concerned case officers from participating schools). The mode of administration of the test medication is by taking the required amount of the gel on the palms (up to 8g/day) and spreading it over the infested skin areas until it provides a full coverage of the affected area (skin surface of the feet up to the ankle) and the feet will then be left for 15 minutes to allow the medication to dry.
Intervention code [1] 315994 0
Treatment: Drugs
Comparator / control treatment
Control group-treatment of tungiasis with 0.05% potassium permanganate (KMnO4) solution

The feet of the participants will be washed with water and soap, dried with a clean towel, and the participants’ toenails will be clipped to enable easier application of the control medication. Then, 0.05% potassium permanganate solution will be applied twice daily on days 1, 4 and 7. The mode of application is by immersing and bathing the feet of the participants in a bucket containing a required volume of 0.05% potassium permanganate solution for 15 minutes. After air-drying the feet (for about 15 mins), vaseline will be applied to soften the skin, which may get rough and irritated after bathing with potassium permanganate solution.
Control group
Active

Outcomes
Primary outcome [1] 321895 0
Proportion of non-viable fleas

Determination of viability of the sand flea lesions will be performed using a handheld digital video microscope, assisted with pictorial flipcharts. Expulsion of eggs, excretion of faecal threads, excretion of faecal liquid, and pulsations/contractions in the abdomen of the embedded flea will be considered as four viability signs and lesions with 2 out of 4 viability signs will be recorded viable. Lesions will be considered dead (non-viable) if their viability signs are not detected during the 10 min follow-up examinations. Differences in the proportion of non-viable lesions between test and control groups will be compared and presented with their respective confidence intervals at 95% and p-values.
Timepoint [1] 321895 0
Day 10 (9 days after the first treatment).
Secondary outcome [1] 376611 0
Acute morbidity evaluation

The severity score for acute morbidities (SSAT; which includes typical signs of local inflammation, the presence of suppuration, ulcers and fissures) will be assessed using a validated scoring system designed for tungiasis morbidity assessment.
In addition to SSAT, a visual analogue scale (VAS) called the ‘Itch-man scale’-- a 5-point pictorial Likert scale, validated for paediatric burn survivors, will be adopted to evaluate itching. Finally, a 4 point pictorial scale, validated in paediatric tungiasis patients will be adopted to assess the pain, as well as pain-related and itching related sleep disturbances (QoL assessment).
Timepoint [1] 376611 0
Days 0 (baseline), 5 and 10 (post treatment)
Secondary outcome [2] 376612 0
Proportion of participants with side effects (adverse events)

Safety will be assessed through evaluation of treatment related adverse events and skin irritation. Participants/caregivers (in person or on the phone) will be asked about the occurrence of any solicited or unsolicited adverse reactions to the treatment during each follow-up visit. The trial team (clinical officer and health officers) will also carefully follow-up the trial participants on a regular basis at the trial site, until the end of trial period. This will be done using a pre-specified list of possible AEs, including local adverse reactions (swelling, stinging/burning, itching, induration, erythema) and systemic adverse reactions (fever, nausea and headache). Caregivers of participants will also be given a diary card to record ongoing solicited adverse events. The severity of the adverse events will be categorized as mild, moderate and severe according to common terminology criteria for adverse events (CTCAE) v5.0 guideline
Timepoint [2] 376612 0
Days 1 (PM), 4, 5, 7 and 10 (post-treatment)

Secondary outcome [3] 376616 0
Participant acceptability of the trial intervention/s

Participants/caregivers will be asked to rate the acceptability of the treatment in terms of effectiveness, side effects, convenience, and overall satisfaction on a 0-5 visual analogue scale.
Timepoint [3] 376616 0
Day 10 (9 days after the first treatment).


Eligibility
Key inclusion criteria
1. Children aged 6-15 years with at least 1 viable (stage II and Stage III) lesions according to the Fortaleza classification and a maximum of 2 viable sand flea lesions will be targeted.
2. Children whose legal guardians are willing to give informed written consents after having been oral and written informed about benefits and potential risks of the trial
Minimum age
6 Years
Maximum age
15 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Children with cluster lesions and manipulated lesions.
2. Children with complicated lesions requiring antibiotic treatment. They will be referred to the nearby health facilities for appropriate clinical management.
3. Children whose guardian/parents intend to change their place of residence during the study period
4. Children with known history of allergy to any of the study medications (Tea Tree Oil or other essential oils and potassium permanganate)
5. Individuals have/had systemic or topical drugs or medications, including systemic antibiotics, which may interfere with the study results (based on clinical team's assessment).

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)
Allocation concealment will be performed using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
After consent is given and the eligibility criteria is met, participants will be allocated to either the test or control groups (in a 1:1 ratio) using a predetermined, computer generated randomisation schedule. This randomisation schedule will be kept secured by an independent statistician who is otherwise not directly involved in the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Bathing a foot in KMnO4 solution may change the colour of the skin to dark purple. This may potentially allow the trial participants and clinical assessors to distinguish between the trial interventions. However, a blind assessment of photographs of tungiasis lesions by an expert panel of clinicians, during the data analysis phase would prevent any likelihood of investigator bias in assessments.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The study aims to test the clinical safety and efficacy of 5% (v/w) tea tree oil (TTO) gel for tungiasis. There have been no clinical trials, which explored tea tree oil (TTO) or its formulation for tungiasis. Hence, the study sample size has been calculated based on data from the existing observational studies on tungiasis, findings from similar trials exploring other tungiasis treatments, findings of studies (in vitro and in vivo) on TTO against other ectoparasites, and the clinical expertise of the study team. The sample size calculations are based on the primary outcome measurement. Calculations are based on the assumptions that 0.05% potassium permanganate solution (i.e. the control treatment) will have a 40% efficacy, and the 5% (v/w) tea tree oil (TTO) gel will have a 70% efficacy at 10 days. To enable the detection of this 30% difference with at least 80% power at a significance level of 5%, a sample size of 40 participants per arm (88 in total accounting for 10% attrition as seen in similar settings) are required.

For each outcome, the number of evaluable children in each treatment group will be presented. Categorical (qualitative) variables will be summarised using frequency and percentage. Metric (quantitative – continuous or discrete) variables will be summarised using mean and standard deviation or median and interquartile range, after applying a Shapiro-Wilk test. This test will be used to assess the normality of the distribution of outcome variables for both groups. Significantly skewed variables will be further assessed for transformation and analysed parametrically or non-parametrically as appropriate, whereas, normally distributed variables will be assessed using a student’s t-test for unpaired samples. Within-group differences, on the other hand, will be assessed using a student’s t-test for paired samples and a Wilcoxon signed-rank test for normally distributed data and for non-normally distributed data, respectively. The size of the treatment effect for primary and secondary outcome measures will be presented as relative and absolute risk reductions with their respective confidence intervals at 95%. A detailed analysis plan will be approved by all investigators prior to any data analysis. The data will be analysed by blinding the study statistician to the treatment allocation. To avoid bias, all statistical analyses will be performed based on an "intention to treat (ITT)" approach. The ITT population will include all randomised participants treated or not, and any participants who withdraw prematurely or poorly comply with the protocol. Results will be considered significant if p value is less than or equal to 0.05. All data will be reported in accordance with the Consolidated Standards of Reporting Trial (CONSORT) guidelines.

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] 22014 0
Kenya
State/province [1] 22014 0
Kisii and Nyamira counties, south-western Kenya

Funding & Sponsors
Funding source category [1] 304203 0
University
Name [1] 304203 0
University of Canberra
Address [1] 304203 0
University of Canberra
University of Canberra
Building 1/11
Kirinari St,
Bruce
ACT 2617

Country [1] 304203 0
Australia
Primary sponsor type
University
Name
University of Canberra
Address
University of Canberra
Building 1/11
Kirinari St,
Bruce
ACT 2617
Australia
Country
Australia
Secondary sponsor category [1] 304435 0
None
Name [1] 304435 0
Address [1] 304435 0
Country [1] 304435 0
Other collaborator category [1] 281020 0
Charities/Societies/Foundations
Name [1] 281020 0
Global School Partners (GSP)
Address [1] 281020 0
GSP-Kenya Chapter
C/ Riamajeshi Bright Start Academy
Sotik Ikonge Road
Nyamira
0800
Kenya
Country [1] 281020 0
Kenya
Other collaborator category [2] 281051 0
Charities/Societies/Foundations
Name [2] 281051 0
Global School Partners (GSP)
Address [2] 281051 0
GSP-Australia Chapter
Deakin
ACT, 2603
Australia
P.O. Box 9421
Country [2] 281051 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304670 0
University of Canberra Human Ethics Research Committee
Ethics committee address [1] 304670 0
Research Services Office
Building 1 Room D83
Kirinari Street, Bruce
University of Canberra, ACT, 2617
Ethics committee country [1] 304670 0
Australia
Date submitted for ethics approval [1] 304670 0
09/07/2019
Approval date [1] 304670 0
28/08/2019
Ethics approval number [1] 304670 0
20192114

Summary
Brief summary
This trial aims to investigate the safety and efficacy of a proprietary tea tree gel (TTO) formulation (5% v/w) in comparison with an active comparator (i.e. 0.05% w/v potassium permanganate solution) for the treatment of tungiasis in children, over a 10-day period. TTO-gel is a water-based, transparent, skin formulation with excellent spreading properties and pleasing aesthetic characteristics. Unlike other tungiasis treatments, the TTO proprietary treatment offers a unique combination of parasiticidal, antibacterial, wound-healing, anti-inflammatory and anti-itch properties. We hypothesize that the TTO-gel is likely to be more effective than the control medication in treating tungiasis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97798 0
Mr Solomon Abrha Bezabh
Address 97798 0
Faculty of Health
University of Canberra
Building 12 Level C Office 22
Kirinari Street
Bruce ACT 2601
Country 97798 0
Australia
Phone 97798 0
+61 2 62068928
Fax 97798 0
Email 97798 0
Solomon.Bezabh@canberra.edu.au
Contact person for public queries
Name 97799 0
A/Prof Jackson Thomas
Address 97799 0
Faculty of Health
University of Canberra
Building 12 Level D Office 36
Kirinari Street
Bruce ACT 2601
Country 97799 0
Australia
Phone 97799 0
+61 2 62068928
Fax 97799 0
+61 2 62068928
Email 97799 0
Jackson.Thomas@canberra.edu.au
Contact person for scientific queries
Name 97800 0
A/Prof Jackson Thomas
Address 97800 0
Faculty of Health
University of Canberra
Building 12 Level D Office 36
Kirinari Street
Bruce ACT 2601
Country 97800 0
Australia
Phone 97800 0
+61 2 62068928
Fax 97800 0
+61 2 62068928
Email 97800 0
Jackson.Thomas@canberra.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
The ethical approval for this study requires the individual participant data to be kept confidential. However, the deidentified pooled data per intervention will be made available through open access research publications.

What supporting documents are/will be available?
No other documents available
Summary results
No Results