Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000403831
Ethics application status
Approved
Date submitted
11/02/2021
Date registered
12/04/2021
Date last updated
14/04/2022
Date data sharing statement initially provided
12/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Tripalma™ for the Topical Treatment of Impetigo
Scientific title
Randomised Controlled Feasibility Study of Tripalma™ for the Topical Treatment of Impetigo
Secondary ID [1] 303219 0
MBS01
Universal Trial Number (UTN)
U1111-1263-7055
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Impetigo 320373 0
Condition category
Condition code
Skin 318274 318274 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to receive either 1% H2O2 (Crystaderm) or a formulation containing 2% Palmarosa oil and 2% Manuka oil ß-triketones (Tripalma).

The topical treatment will be applied twice a day for 7 days. Each application will be preceded by a simple wound care process. Using surgical gloves, the impetigo lesion will be cleansed using saline and sterile gauze, softening the scab and removing where possible. A sufficient quantity of topical study treatment will be applied to provide a thin covering of the entire lesion and two millimeters of surrounding skin. This will be followed by the application of an occlusive dressing where practical. At visit one wound care and treatment application will be done by the pharmacist. During the rest of the intervention period, the parent/guardian will apply the topical treatment to the participant.

The parent/guardian will complete a twice-daily online diary to capture a photograph of the impetigo lesion, monitor adherence, and adverse events. This diary is anticipated to take 5-10 minutes to complete and will be completed during treatment application to guide the parent/guardian through the process.
Intervention code [1] 319531 0
Treatment: Drugs
Comparator / control treatment
Active control: Topical antiseptic 1% w/w H2O2) (Crystaderm)

Composition: 1% w/w H2O2, Glyceryl laurate, Glyceryl myristate, PEG-100 stearate, Propylene glycol, Anhydrous citric acid, Sodium hydroxide, Sulphuric acid, Sodium oxalate, Salicyclic acid, Disodium edetate, Sodium pyrophosphate, Sodium stannate, Purified Water
Control group
Active

Outcomes
Primary outcome [1] 326257 0
Proportion of screened participants that were randomised. This will be assessed by audit of study database. It will be recorded in the database any time the screening statement is read to potential participants,
Timepoint [1] 326257 0
Day of participant screening and randomisation (Day 1)
Secondary outcome [1] 390771 0
The proportion of participants reaching clinical success in each group. Clinical success defined as SIRS sub-domain scores of 0 in the blistering, pus, crust and itch/pain sub-domains and greater than or equal to 1 in the erythema/inflammation domain with no requirement for treatment escalation to a topical/oral antibiotic
Timepoint [1] 390771 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [2] 390772 0
The severity of infection of impetigo lesion, assessed using the skin infection rating scale (SIRS)
Timepoint [2] 390772 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [3] 390773 0
Time to clinical success. Clinical success defined as SIRS sub-domain scores of 0 in the blistering, pus, crust and itch/pain sub-domains and greater than or equal to 1 in the erythema/inflammation domain with no requirement for treatment escalation to a topical/oral antibiotic
Timepoint [3] 390773 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [4] 390774 0
Time to score of 0 in each SIRS subdomain
Timepoint [4] 390774 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [5] 390775 0
Proportion of participants that require rescue antibiotics (topical and/or oral) assessed by participant and parent/guardian self-report.
Timepoint [5] 390775 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [6] 390776 0
Proportion of participants that require topical antibiotics for unresponsive impetigo, assessed by participant and parent/guardian self-report.
Timepoint [6] 390776 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [7] 390777 0
Proportion of participants that require systemic antibiotics for unresponsive impetigo, assessed by participant and parent/guardian self-report.
Timepoint [7] 390777 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [8] 390778 0
Proportions of withdrawals for worsening impetigo between groups, assessed by audit of study database.
Timepoint [8] 390778 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [9] 390779 0
Proportion of participants reporting the development of additional impetigo lesions during the treatment period, assessed by accessing participant self-report collected in online diary.
Timepoint [9] 390779 0
Daily up to day 8 post-intervention commencement.
Secondary outcome [10] 390780 0
Numerical Rating Scale score for the acceptability of Tripalma for the treatment of impetigo (1 unacceptable to 10 acceptable)
Timepoint [10] 390780 0
Day 8 or 9 post-intervention commencement (Day after final treatment application)
Secondary outcome [11] 390781 0
Proportions of serious adverse events between treatment groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5)
Timepoint [11] 390781 0
Day 21 post-intervention commencement
Secondary outcome [12] 390784 0
Proportion of randomised participants who completed the study, assessed by audit of study database
Timepoint [12] 390784 0
Day 21 post-intervention commencement
Secondary outcome [13] 392830 0
Proportion of cutaneous and systemic adverse events between treatment groups, assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5)
Timepoint [13] 392830 0
Day 21 post-intervention commencement

Eligibility
Key inclusion criteria
- Willing to provide written informed consent (parent(s)/guardian(s))
- Willing to provide written informed assent (participants aged 7-14, assent is not required for participants younger than 7.)
- Participant is aged between 2 and 14 years of age, inclusive
- Doctor, Nurse or Pharmacist confirmed episode of impetigo
- Three or fewer impetigo lesions at day 1 with one in area participants and caregivers are comfortable to photograph. Presence of impetigo at one distinct anatomical location will be classified as one lesion (e.g. mouth, nose, right arm)
- Onset of disease within 48 hours of visit one
- Current impetigo lesion remains untreated with any topical or systemic therapy, simple wound cleansing permitted
- Skin Infection Rating Scale (SIRS) score of 3 or more, with a score of 1 or more in the pus/exudate domain.
- Participant and parent/caregiver is willing to stop all moisturisers, soap products and/or other skin barrier cream or emulsion treatments from being applied to the affected areas of skin during the study period. Immersion in bath water or a shower is permitted
- Participant and parent/caregiver are able to be contacted by telephone for a follow up visit 21 days after they enrol in the study
- Participant and parent/caregiver must have internet access on a smartphone for completing the online study diaries and the ability to take a photo of the infected area on their phone twice a day.
Minimum age
2 Years
Maximum age
14 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Cellulitis in area of lesion or any other location
- Tympanic temperature > 38°C
- Current requirement or use of antibiotics for the treatment of any condition
- Use of any topical antibiotic within the last two weeks
- Use of any systemic antibiotic within the last four weeks
- Any use of topical steroid within 10cm of the active lesion under assessment
- Any use of topical antihistamine within 10cm of the active lesion under assessment
- Any use of oral antihistamine that is not established and regular within three weeks of enrolment
- Other skin condition which may affect the assessment of impetigo severity
- History of allergy or hypersensitivity to study treatment ingredients and wound dressing.
- Participation in a clinical trial involving an investigational product during the last one month
- Meets any High Index of Suspicion criteria for COVID-19 as per current Ministry of Health guidance
- Cold/flu-like symptoms, fever, or unexplained shortness of breath in the past 14 days.
- Any other condition which, at the investigators’ discretion, it is believed may present a safety risk or impact upon the ability of the participant to complete the study.

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)
Participants will be randomised in a 1:1 ratio to receive either the investigational product or active control. Randomisation will take place electronically within the REDCap CDMA, and provide the study site with a box ID number. The corresponding box will then be dispensed to the treatment. Investigational product and active control will be dispensed in matching plain packaging.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A statistician generated block randomisation schedule, using a block size of four.
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
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size of 50 was chosen to assess the proportion of screened participants randomised into the trial. If a minimum of 100 were approached, assuming a recruitment rate of 50% or less, an achieved participation of 50 participants has 80% power, one-sided alpha to rule out a recruitment rate of less than 37%. A sample size of 25 participants per treatment arm also allows for variance estimates to be made with adequate precision based on a chi-square distribution.

Analysis will be performed for both per-protocol (PP) population and intention-to-treat (ITT) population. ITT population consists of all participants randomised who applied IMP at Visit 1 who have post-baseline data for SIRS. Including randomised participants subsequently found to be ineligible. PP population consists of all participants with at least 80% of completed data within diary window, including primary outcome with no significant protocol deviations determined to influence SIRS score.

Primary outcome analysis will be proportion expressed as a percentage and associated confidence interval.

Data will be analysed using STATA, SAS and/or SPSS software. p-value <0.05 will be considered statistically significant.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
4/06/2021
Actual
Date of last participant enrolment
Anticipated
21/04/2022
Actual
Date of last data collection
Anticipated
5/05/2022
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment outside Australia
Country [1] 23393 0
New Zealand
State/province [1] 23393 0

Funding & Sponsors
Funding source category [1] 307628 0
Commercial sector/Industry
Name [1] 307628 0
Manuka Bioscience
Country [1] 307628 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Manuka Biosciences
Address
Manuka Bioscience
300 Richmond Road,
Grey Lynn, Auckland, 1021
Country
New Zealand
Secondary sponsor category [1] 308314 0
None
Name [1] 308314 0
Address [1] 308314 0
Country [1] 308314 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307671 0
Central Health and Disability Ethics Committee (HDEC)
Ethics committee address [1] 307671 0
Ethics committee country [1] 307671 0
New Zealand
Date submitted for ethics approval [1] 307671 0
04/03/2021
Approval date [1] 307671 0
12/04/2021
Ethics approval number [1] 307671 0
21/CEN/78

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

Contacts
Principal investigator
Name 108082 0
Dr Alex Semprini
Address 108082 0
Medical Research Institute of New Zealand,
Level 7 Clinical Services Building,
Wellington Hospital,
Riddiford Street, Newtown
Wellington, 6021
Country 108082 0
New Zealand
Phone 108082 0
+64 4 804 0260
Fax 108082 0
Email 108082 0
[email protected]
Contact person for public queries
Name 108083 0
Alex Semprini
Address 108083 0
Medical Research Institute of New Zealand,
Level 7 Clinical Services Building,
Wellington Hospital,
Riddiford Street, Newtown
Wellington, 6021
Country 108083 0
New Zealand
Phone 108083 0
+64 4 804 0260
Fax 108083 0
Email 108083 0
[email protected]
Contact person for scientific queries
Name 108084 0
Alex Semprini
Address 108084 0
Medical Research Institute of New Zealand,
Level 7 Clinical Services Building,
Wellington Hospital,
Riddiford Street, Newtown
Wellington, 6021
Country 108084 0
New Zealand
Phone 108084 0
+64 4 804 0260
Fax 108084 0
Email 108084 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data underlying published results only.
When will data be available (start and end dates)?
Data will be available after the publication of the manuscript.
Available to whom?
Data will be available to researchers who provide a methodologically sound proposal.
Available for what types of analyses?
For purposes of achieving specific aims outlined in the proposal.
How or where can data be obtained?
Proposals should be directed to Dr Alex Semprini via emial ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



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.