Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000648527
Ethics application status
Approved
Date submitted
10/06/2015
Date registered
23/06/2015
Date last updated
22/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
5% Aciclovir or Honevo(Trademark) as a treatment for cold sores
Scientific title
In adult patients with cold sores will topical medical grade honey reduce healing time compared to topical 5% aciclovir alone.
Secondary ID [1] 286312 0
None
Universal Trial Number (UTN)
U1111-1170-1537
Trial acronym
KH10
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Herpes Labialis 294410 0
Condition category
Condition code
Skin 294716 294716 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Topical medical grade Kanuka honey applied to the affected area five times daily for fourteen days or until skin returns to normal, whichever is sooner. A participant diary will record applications during the treatment period.
Intervention code [1] 291356 0
Treatment: Other
Comparator / control treatment
Standard treatment is 5% topical aciclovir cream. Participants in the control arm will apply 5% topical aciclovir to the affected area five times daily for fourteen days or until the skin returns to normal.
Control group
Active

Outcomes
Primary outcome [1] 294479 0
Healing time (from randomization to the return to normal skin) as measured daily by participant reported cold sore stage from a pictorial chart.
Timepoint [1] 294479 0
Daily up to fourteen days.
Secondary outcome [1] 313423 0
Total healing time, defined as the time from development of first sign or symptom to the return to normal skin, as measured daily by participant reported cold sore stage from a pictorial chart.
Timepoint [1] 313423 0
Daily up to fourteen days.
Secondary outcome [2] 313424 0
Total healing time stratified by stage of the lesion at onset of treatment, as measured daily by participant reported cold sore stage from a pictorial chart.
Timepoint [2] 313424 0
Daily up to fourteen days.
Secondary outcome [3] 313425 0
Highest pain severity as recorded daily by participants using the scale 'o - 10' with 0 being no pain and 10 being most pain.
Timepoint [3] 313425 0
Daily up to fourteen days.
Secondary outcome [4] 313426 0
Time to pain resolution (defined as the time from first experiencing pain to total resolution of pain), as recorded daily by participants using the scale '0 - 10' with 0 being no pain and 10 being most pain.
Timepoint [4] 313426 0
Daily up to fourteen days.
Secondary outcome [5] 341016 0
Time to stage 4 from randomisation, as measured daily by participant reported cold sore stage from a pictorial chart.
Timepoint [5] 341016 0
Daily up to fourteen days
Secondary outcome [6] 341017 0
Time to stage 7 from stage 4, as measured daily by participant reported cold sore stage from a pictorial chart.
Timepoint [6] 341017 0
Daily up to fourteen days
Secondary outcome [7] 341018 0
Acceptability of treatments as measured by a numerical rating scale.
Timepoint [7] 341018 0
At study follow up between day 15 and 35, on completion.

Eligibility
Key inclusion criteria
Aged 16 years or over at the time of enrolment.
Presentation to a pharmacy for treatment of a cold sore.
First cold sore symptoms (including prodromal symptoms e.g. tingling/pain) within 72 hours.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any participant who is pregnant or breastfeeding.
Known or suspected allergy to honey, bees, aciclovir and/or glycerin.
Any other condition which, at the investigators' discretion, it is believed may present a safety risk or impact the feasibility of the study or the study results.
Patient has used oral aciclovir or other antiviral medicine, or any topical treatment, medical or complementary, on the current sore.
Participants planning to take or use any concomitant medications, which in the opinion of the investigator, could affect the cold sore during the course of the trial. This includes any topical product, medical or complementary, on the cold sore, oral aciclovir or other antiviral medicine, oral complementary medicines for cold sores, such as lysine supplements.

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)
Eligible participants will be randomised into the study in a 1:1 ratio, one arm receiving topical medical grade Kanuka honey and the second arm receiving topical 5% aciclovir. Both groups will apply their specific treatment five times a day. Each pharmacy site will be provided an allocation of randomised patient packs containing the treatment allocation and patient diary. Pharmacists will dispense the appropriate treatment as randomised to the participant upon opening of the concealed envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Biostatistitian to generate randomisation schedule.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Participants and study site staff will not be blinded to the allocated treatment due to the nature of the investigational product. Data analysis will be conducted by a statistician blinded to the allocation.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Assuming that the median control duration of symptoms is five days and looking to achieve a one day median difference, with associated Hazard ratio of 1.25, 423 participants would be needed per arm of treatment, therefore the total required is 846. As this is a short study lasting only for the duration of one cold sore episode, then drop-outs from the study should be low, and so assuming that the drop-out rate is around 10%, then 950 participants will be randomized. This study size is consistent with similar 2-arm or 3-arm cold sore studies have required around 300-350 patients per treatment arm. Kaplan-Meier survival plots and estimates of median healing times and Cox Proportional Hazards with a random effect for participants to take into account the parallel design, compared time to healing and pain duration between treatments. Paired t-tests will be used to compare the continuous variables.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/07/2015
Actual
10/09/2015
Date of last participant enrolment
Anticipated
20/12/2017
Actual
20/12/2017
Date of last data collection
Anticipated
Actual
15/01/2018
Sample size
Target
950
Accrual to date
Final
952
Recruitment outside Australia
Country [1] 6718 0
New Zealand
State/province [1] 6718 0

Funding & Sponsors
Funding source category [1] 290883 0
Commercial sector/Industry
Name [1] 290883 0
Honeylab Ltd
Country [1] 290883 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Honeylab Ltd
Address
HoneyLab Ltd
Queens Wharf Business Centre
PO Box 10-799
Wellington, 6011
Country
New Zealand
Secondary sponsor category [1] 289566 0
None
Name [1] 289566 0
Address [1] 289566 0
Country [1] 289566 0
Other collaborator category [1] 278386 0
Charities/Societies/Foundations
Name [1] 278386 0
Medical Research Institute of New Zealand
Address [1] 278386 0
Medical Research Institute of New Zealand
Private Bag 7902
Wellington 6242
Country [1] 278386 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292485 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 292485 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington
Ethics committee country [1] 292485 0
New Zealand
Date submitted for ethics approval [1] 292485 0
Approval date [1] 292485 0
09/06/2015
Ethics approval number [1] 292485 0
15/NTB/93

Summary
Brief summary
A recent pilot study has shown that medical grade Kanuka honey is an acceptable treatment for cold sores. This large-scale randomised controlled trial has the potential to demonstrate a combination product of Kanuka honey and aciclovir (the current topical standard treatment) as an effective treatment for cold sores. In this study 950 participants seeking over the counter treatment for a cold sore will be randomised to receive either topical medical grade Kanuka honey or topical 5% aciclovir alone. Participants will apply their treatment five times a day for fourteen days or until the skin returns to normal, whichever is sooner. Participants will complete a paper or online diary recording the number of applications, the pain suffered that day and the stage of the cold sore based on a pictorial chart. At day fourteen each participant will receive a follow up telephone call to record adverse events and obtain narrative feedback.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 495 495 0 0
/AnzctrAttachments/368118-HDEC Letter 15NTB93 Approved FULL Application with Non Standard Conditions.pdf

Contacts
Principal investigator
Name 55530 0
Dr Irene Braithwaite
Address 55530 0
Medical Research Institute of New Zealand Private Bag 7902 Wellington
6242
Country 55530 0
New Zealand
Phone 55530 0
+64 4 8050147
Fax 55530 0
+64 4 3895707
Email 55530 0
[email protected]
Contact person for public queries
Name 55531 0
Dr Alex Semprini
Address 55531 0
Medical Research Institute of New Zealand Private Bag 7902 Wellington
6242
Country 55531 0
New Zealand
Phone 55531 0
+648050260
Fax 55531 0
+64 (0) 9 353 1800
Email 55531 0
[email protected]
Contact person for scientific queries
Name 55532 0
Dr Alex Semprini
Address 55532 0
Medical Research Institute of New Zealand Private Bag 7902 Wellington
6242
Country 55532 0
New Zealand
Phone 55532 0
+64 4 8050147
Fax 55532 0
+64 4 8050147
Email 55532 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseKanuka honey versus aciclovir for the topical treatment of herpes simplex labialis: A randomised controlled trial.2019https://dx.doi.org/10.1136/bmjopen-2018-026201
Dimensions AIProtocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting2017https://doi.org/10.1136/bmjopen-2017-017766
Dimensions AICurrent landscape in antiviral drug development against herpes simplex virus infections2022https://doi.org/10.1002/smmd.20220004
N.B. These documents automatically identified may not have been verified by the study sponsor.