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Trial registered on ANZCTR


Registration number
ACTRN12618000890235
Ethics application status
Approved
Date submitted
26/04/2018
Date registered
28/05/2018
Date last updated
29/07/2019
Date data sharing statement initially provided
10/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A topical cold sore treatment containing St John's Wort, Calendula and Copper
Scientific title
A randomised, double blind, placebo controlled trial of a topical treatment containing Hypericum perforatum, Calendula officinalis and copper sulfate on herpes simplex labialis (HSL).
Secondary ID [1] 294726 0
None
Universal Trial Number (UTN)
U1111-1233-2426
Trial acronym
SC001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Herpes Simplex Labialis 307607 0
Condition category
Condition code
Skin 306662 306662 0 0
Dermatological conditions
Alternative and Complementary Medicine 307007 307007 0 0
Herbal remedies
Infection 307008 307008 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
One topical application (0.5-0.7ml) of the intervention will be applied to the lesion at the first pharmacy visit. The application will be performed by either the pharmacist or the participant, at the participant's discretion.

This single application of the topical treatment containing Hypericum perforatum (St John's Wort), Calendula officinalis (Calendula) and copper sulfate will be applied within 48 hours of the first prodromal symptoms or first clinical signs of herpes simplex labialis. There is only one single dose of the topical treatment applied at the first pharmacy visit with no further applications of the treatment during the 14 days or until the skin returns to normal.

Participants will record in a daily online diary, cold sore progression, levels of pain and symptoms and any adverse events during the treatment period.
Intervention code [1] 301018 0
Treatment: Other
Comparator / control treatment
Placebo control: one topical application of colour, smell and taste matched placebo within 48 hours of the first prodromal symptoms or at the first clinical signs of herpes simplex labialis.

The placebo is identical to the intervention with the exception of the active ingredients: Hypericum perforatum (St John's wort), Calendula officinalis (Calendula) and copper sulfate.

The placebo contains: Blue dye (colour matched to the treatment); Aloe Vera, Glycerol, Vitamin E, Hydroxyethycellulose, polysorbate, purified water.
Control group
Placebo

Outcomes
Primary outcome [1] 305671 0
The efficacy of one single topical application (0.5-0.7ml) of the treatment in the reduction of episode duration of herpes simplex labialis (HSL), measured in days from the onset of HSL symptoms to healed skin.
Timepoint [1] 305671 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [1] 346117 0
The effect of the topical treatment on the progression of the HSL to ulcerative vs non-ulcerative lesions, assessed by the percentage of lesions in each group that progress to an ulcerative stage. This will be self-reported using a supplied chart with photographs of the stages of wound healing.
Timepoint [1] 346117 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [2] 346120 0
The effect of the topical treatment on the duration of the herpes simplex labialis wound healing, assessed by the median duration in each group of onset to drying up and healing in days (self-reported).
Timepoint [2] 346120 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [3] 346121 0
The effect of the topical treatment on pain during the disease course of the herpes simplex labialis, assessed for each group, on a ten point ordinal scale of 0 - 10; (where 0 = no pain and 10 = severe pain) (self-reported).
Timepoint [3] 346121 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [4] 346122 0
Participant level of satisfaction of the topical treatment. The survey is designed specifically for this study.
Timepoint [4] 346122 0
Participants will receive a survey 2 days after their final pharmacy (clinical) visit.
Secondary outcome [5] 346123 0
The degree of safety of the topical treatment.
Timepoint [5] 346123 0
Participants will receive an exit survey 2 days after the final pharmacy (clinical) visit. The survey is designed specifically for this study.
Secondary outcome [6] 347220 0
The effect of the topical treatment on burning sensation during the disease course of the herpes simplex labialis, assessed for each group, on a four point ordinal scale of 0 - 4; (where 0=not present; 1=mild; 2=moderate; 3=severe) (self-reported).
Timepoint [6] 347220 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [7] 347221 0
The effect of the topical treatment on itching sensation during the disease course of the herpes simplex labialis, assessed for each group, on a four point ordinal scale of 0 - 4; (where 0=not present; 1=mild; 2=moderate; 3=severe) (self-reported).
Timepoint [7] 347221 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [8] 347222 0
The effect of the topical treatment on tingling sensation during the disease course of the herpes simplex labialis, assessed for each group, on a four point ordinal scale of 0 - 4; (where 0=not present; 1=mild; 2=moderate; 3=severe) (self-reported).
Timepoint [8] 347222 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.
Secondary outcome [9] 347223 0
The degree of acceptability of the topical treatment.
Timepoint [9] 347223 0
Participants will receive an exit survey 2 days after the final pharmacy (clinical) visit. The survey is designed specifically for this study.
Secondary outcome [10] 347226 0
The effect of the topical treatment on the duration of the herpes simplex labialis wound healing, assessed by the median duration in each group of onset to redness in days (self-reported).
Timepoint [10] 347226 0
Recorded by participant every day for up to 14 days after the application of the topical treatment.

Eligibility
Key inclusion criteria
- Females and males from the general population.
- Aged 18-65 years.
- Previous clinical history of herpes simplex labialis (HSL), with at least 3 prior episodes.
- Onset of prodromal or clinical symptoms of HSL within the past 48 hours.
- Primary lesion is within 1cm of the lip.
- Willing to provide informed consent and adhere to the protocol.
- Has internet access (either via a mobile or computer) for completing online forms
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of immunodeficiency, immunosuppression or autoimmune disorder (including HIV, rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, inherited immune deficiency, immune suppression for organ transplantation, immune suppression medication for other inflammatory disorders)
- Individuals with an acute condition not related to the study condition (current viral infections such as cold and flu).
- Use of other antiviral agents (including herbal medications), anti-inflammatory medications or steroids during or within two weeks prior to the treatment period.
- Sensitivity to any of the ingredients in the study treatment.
- Use of any topical agents (including cosmetics, lip balms, sunscreens, etc.) or cosmetic procedures (such as chemical peels or microdermabrasion) on the prodromal or lesion area during the treatment period.
- Mechanical disruption (i.e., scrubbing, lancing, shaving, etc.) of the prodromal area or lesion prohibited during the treatment period.
- Female participants who are lactating, pregnant or planning to become pregnant during the next 14 days.

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)
After signing the informed consent document and satisfying the eligibility criteria participants will be randomised in a 2:1 ratio to either the active treatment group or the placebo control. A 2:1 ratio was chosen to improve recruitment rates as potential participants are actively seeking treatment when attending the pharmacy, therefore a greater chance of being allocated active treatment will increase recruitment and retention rates. Blocked randomisation, with a block size of 6 will be undertaken. Individual study sites will be able to randomise via a web portal or via text message. Randomisation will provide the study site with a box ID number, the corresponding box will then be dispensed to the participant. There will be no disclosure of group allocation to any site staff or participants.
Once randomised, participants will be given one vial of the active topical treatment, or a colour, viscosity, taste and smell matched placebo in matching plain packaging. The investigator or the participant, if they choose, will then apply the intervention once, in view of the investigator, then return the vial and packaging for disposal.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Blocked randomisation, with a block size of 6 will be undertaken. Individual study sites will be able to randomise via a web portal or via text message.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Efficacy analyses will be performed for both the intent-to-treat (ITT) population and per-protocol (PP) population. The ITT population will consist of all participants. The PP population will exclude all participants in the ITT population who have missing information.

Continuous data will be summarized using descriptive statistics including the number of observations used in the calculation (n), mean, standard deviation (SD), minimum, median and maximum.

The primary analysis for the primary outcome will be median duration of episode, from the stage at presentation to the clinical site until healing, compared between groups using a two tailed t-test. Secondary outcomes will include Cox proportional hazards for time to healing and time of wound duration, Kaplan-Meier survival plots. NRS pain scores and symptoms will be analysed using a linear mixed model, with time and group as fixed factors. Multilevel, multivariate analysis will be conducted with different factors including country, gender and number of previous episodes. Results will be documented with p values and 95% confidence intervals.

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

Recruitment
Recruitment status
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)
NSW
Recruitment outside Australia
Country [1] 10354 0
New Zealand
State/province [1] 10354 0

Funding & Sponsors
Funding source category [1] 299334 0
Commercial sector/Industry
Name [1] 299334 0
Sci-Chem International Pty Ltd
Address [1] 299334 0
Unit 12, 55-57 Newton Rd, Wetherill Park, NSW, 2164.
Country [1] 299334 0
Australia
Primary sponsor type
University
Name
Western Sydney University
Address
NICM Health Research Institute
Locked Bag 1797, Penrith NSW 2751
Country
Australia
Secondary sponsor category [1] 298599 0
Charities/Societies/Foundations
Name [1] 298599 0
Medical Research Institute of New Zealand
Address [1] 298599 0
Private Bag 7902, Wellington 6242
Country [1] 298599 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300239 0
Western Sydney University Human Research Ethics Committee
Ethics committee address [1] 300239 0
Locked Bag 1797, Penrith NSW 2751
Ethics committee country [1] 300239 0
Australia
Date submitted for ethics approval [1] 300239 0
22/05/2018
Approval date [1] 300239 0
04/07/2018
Ethics approval number [1] 300239 0
H12776
Ethics committee name [2] 300243 0
Northern B Health and Disability Ethics Committee
Ethics committee address [2] 300243 0
Ministry of Health
Ethics Department
Freyberg Building
Reception-Ground Floor
20 Aitken Street
Wellington
Ethics committee country [2] 300243 0
New Zealand
Date submitted for ethics approval [2] 300243 0
30/05/2018
Approval date [2] 300243 0
28/08/2018
Ethics approval number [2] 300243 0
18/CEN/151

Summary
Brief summary
The aim of this clinical trial is to test the effectiveness of a topical treatment on facial cold sores (herpes simplex labialis): whether it reduces the duration of healing and the amount of pain and other symptoms. A minimum of 292 male and female participants in Australia and New Zealand, aged from 18 to 65 years, will be randomly assigned to receive either a placebo or a medically approved topical treatment. Participants will attend a participating pharmacy twice to receive the initial assessment, treatment and final assessment by trained pharmacists. Participants will report symptoms and healing progression in an on-line daily diary which researchers will monitor for reports of adverse side effects. We expect the primary outcome to be a reduction in the duration of the cold sore compared to the placebo controlled group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83018 0
Dr Mike Armour
Address 83018 0
Post doctoral Research Fellow,
NICM Health Research Institute
Western Sydney University
Building 22, Campbelltown Campus
Locked Bag 1797
Penrith NSW 2751
Country 83018 0
Australia
Phone 83018 0
+61 2 4620 3345
Fax 83018 0
+61 2 4620 3291
Email 83018 0
m.armour@westernsydney.edu.au
Contact person for public queries
Name 83019 0
Dr Mike Armour
Address 83019 0
Post doctoral Research Fellow,
NICM Health Research Institute
Western Sydney University
Building 22, Campbelltown Campus
Locked Bag 1797
Penrith NSW 2751
Country 83019 0
Australia
Phone 83019 0
+61 2 4620 3345
Fax 83019 0
+61 2 4620 3291
Email 83019 0
m.armour@westernsydney.edu.au
Contact person for scientific queries
Name 83020 0
Dr Mike Armour
Address 83020 0
Post doctoral Research Fellow,
NICM Health Research Institute
Western Sydney University
Building 22, Campbelltown Campus
Locked Bag 1797
Penrith NSW 2751
Country 83020 0
Australia
Phone 83020 0
+61 2 4620 3345
Fax 83020 0
+61 2 4620 3291
Email 83020 0
m.armour@westernsydney.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
Checking standard operating procedures for IPD
What supporting documents are/will be available?
Informed consent form
Ethical approval
Summary results
No Results