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Trial registered on ANZCTR


Registration number
ACTRN12613000062729
Ethics application status
Approved
Date submitted
15/01/2013
Date registered
16/01/2013
Date last updated
16/01/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to compare two different pedal wart treatments.
Scientific title
A randomised controlled pilot study trial to compare the effectiveness of liquid nitrogen cryotherapy and needling in the treatment of pedal cutaneous warts within the population.
Secondary ID [1] 281780 0
nil known
Universal Trial Number (UTN)
U1111-1138-5576
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
pedal warts 288100 0
Condition category
Condition code
Skin 288473 288473 0 0
Other skin conditions
Infection 288483 288483 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The needling treatment involves breaking up the infected skin cells with a hypodermic needle.
This, in theory, creates an immune response which will kill the virus. This process is called cell mediated immunity.
We believe the Cell Mediated Immune Response, as a result of needling, to be created by 1) migration of immune cells to the local area due to an inflammatory response to injury, 2) manual lysing of infected epidermal cells to release the contained human papillomavirus (thereby exposing them to the immune cells), 3) translocating the virus in closer proximity to the papillary skin layer where there is a higher concentration of resident T-lymphocytes and, 4) sensitising the immune system to human papillomavirus antigen resulting in a CMIR against the human papillomavirus.

Needling treatment protocol
1. Local anaesthetic is administered; either local infiltration or block technique depending on the location and size of the wart.
2. Alcohol wipes are used as a disinfectant to clean the surface of the largest pedal wart and surrounding skin to be treated.
3. The wart is then debrided using a scalpel until pin-point bleeding is present.
4. Using a sterile 25-gauge needle the wart is punctured perpendicular to the surface through the spongy stroma and the base of the capsule into the subcutaneous fat.
5. This needling method is repeated, starting at the periphery and working circularly towards the centre of the wart until all of the papillae have been destroyed.
6. The wound is dressed with the Cutiplast. The Participant is supplied with adequate spare dressings.

Injectable Lignocaine or Lidocaine hydrochloride delivered by 25 gauge syringe.
Frequency: Prior to procedure, as required.
Maximum dose: 3mg/kg (up to 200mg) i.e 50kg adult may have 150mg of Lignocaine/Lidocaine.
Preparation: 1 or 2%

Typically in these procedures we would use up to 10ml of 1% lignocaine to achieve local anaesthesia.
In 10ml of 1% lignocaine preparation there is 100 mg of Lignocaine. The maximum recommended dose for a 50kg adult is 150mg.
This shows there is a large window between the doses to be delivered in this procedure and the maximum dose.
Uncommon adverse events associated with the use of local anesthetics include hypotension, bradycardia, arrhythmias, cardiac arrest, muscle twitching, seizures, coma and/or respiratory depression.

Australian Standard Infection Control policies will be in place to reduce any risk of bacterial or fungal infection, however, a certain degree of risk will always be present. Other possible complications such as bleeding, blistering, hindrances of daily activities, stress, and pain will be minimised.
- Bleeding will be controlled by an absorbent padded dressing applied under tension which will apply pressure to the wound and provide comfort for the patient.
- The wound will be monitored closely every two weeks for signs of infection and the Participant managed appropriately if such an event occurs.

Intervention code [1] 286325 0
Treatment: Other
Comparator / control treatment
The control is liquid nitrogen cryotherapy, which is considered a first line, standard therapy for warts. Liquid Nitrogen cryotherapy involves destroying the infected cells through freezing. Freezing the infected tissue will kill the infected skin cells as well as the contained HPV.

Cryotherapy
1. Local anaesthetic is administered if necessary; either local infiltration or block technique depending on the location and size of the wart.
2. Alcohol is used as a disinfectant to clean the surface of the largest pedal wart and surrounding skin to be treated.
3. The wart is then debrided using a scalpel until pin-point bleeding is present.
4. Using a cotton wool swab and liquid nitrogen as the cryogen, the swab is applied to the entire surface of the wart until the lesion turns white (approximately 5-10 seconds).
5. The frozen tissue is then allowed to thaw for 30 seconds and the process is repeated once more.
6. Cutiplast is then applied over the wart. The Participant will be supplied with adequate spare dressings.

Injectable Lignocaine or Lidocaine hydrochloride delivered by 25 gauge syringe.
Frequency: Prior to procedure, as required.
Maximum dose: 3mg/kg (up to 200mg) i.e 50kg adult may have 150mg of Lignocaine/Lidocaine.
Preparation: 1 or 2%

Typically in these procedures we would use up to 10ml of 1% lignocaine to achieve local anaesthesia.
In 10ml of 1% lignocaine preparation there is 100 mg of Lignocaine. The maximum recommended dose for a 50kg adult is 150mg.
This shows there is a large window between the doses to be delivered in this procedure and the maximum dose.
Uncommon adverse events associated with the use of local anesthetics include hypotension, bradycardia, arrhythmias, cardiac arrest, muscle twitching, seizures, coma and/or respiratory depression.


Australian Standard Infection Control policies will be in place to reduce any risk of bacterial or fungal infection, however, a certain degree of risk will always be present. Other possible complications such as bleeding, blistering, hindrances of daily activities, stress, and pain will be minimised.
- Bleeding will be controlled by an absorbent padded dressing applied under tension which will apply pressure to the wound and provide comfort for the patient.
- Blistering after nitrogen cryotherapy treatment will be avoided by using a gentle freezing technique as apposed to an aggressive technique (we will only freeze the wart for approximately five seconds as apposed to an aggressive technique in which the wart would be frozen for thirty seconds). This will also aid in a quicker recovery for the patient.
- The wound will be monitored closely every two weeks for signs of infection and the Participant managed appropriately if such an event occurs.
Control group
Active

Outcomes
Primary outcome [1] 288634 0
The primary outcome of this study was complete regression of the treated, primary wart at twelve weeks post initial treatment.

Regression was clinically defined as the return of normal skin striae.

High resolution, digital photographs were taken of the primary pedal wart at baseline and twelve weeks post initial treatment. A panel of two registered podiatrists, each with over 20 years experience, assessed the photographs. The panel members were blinded to the intervention and independently assessed whether the primary pedal wart had regressed. If the panel members’ outcomes conflicted, a third assessor was called upon to make the final decision.
Timepoint [1] 288634 0
twelve weeks post randomisation
Secondary outcome [1] 300667 0
The relative cosmetic outcome of the primary pedal wart.

The blinded panel members determined this outcome using a numerical rating scale of cosmetic improvement or deterioration.
Timepoint [1] 300667 0
twelve weeks post randomisation
Secondary outcome [2] 300668 0
The regression of any satellite pedal warts at the outcome assessment.

Participants with single warts were excluded from this analysis. The blinded panel independently assessed only satellite pedal warts within the field of view of the photograph, indicating how many satellite pedal warts were present before and how many were present after treatment.
Timepoint [2] 300668 0
twelve weeks post randomisation
Secondary outcome [3] 300669 0
Complete pedal wart regression.

A positive result for this outcome was determined if the panel deemed both the primary pedal wart and all satellite pedal warts in the photographs to be regressed. Participants without satellite pedal warts at baseline were included in the analysis.
Timepoint [3] 300669 0
twelve weeks post randomisation
Secondary outcome [4] 300670 0
Participant centred outcomes.
Participants were asked to rate the pain from their pedal warts on a ten-point verbal rating scale (ten being ‘worst pain imaginable’ and one being ‘no pain’) before receiving treatment at the initial, second and final visits. Participant satisfaction with the treatment at the final follow-up was recorded on a ten-point verbal rating scale (ten being ‘very happy’ and one being ‘very unhappy’). At the final visit, participants ranked their opinion of the cosmetic outcome of the treatment on a ten-point verbal rating scale (ten being ‘much better’ and one being ‘much worse’).
Timepoint [4] 300670 0
twelve weeks post randomisation
Secondary outcome [5] 300671 0
Adverse events. Occurrences of adverse events arising from the treatment were documented at each follow up visit.
Adverse events may include: bacterial infection, hypertrophic scarring, severe blistering, pain for more than three days post treatment and more.
An adverse event would be an unintentional, unexpected outcome as a result of treatment.
Timepoint [5] 300671 0
twelve weeks post randomisation

Eligibility
Key inclusion criteria
Eligible participants had one or more correctly diagnosed pedal cutaneous wart/s and were aged 18 years or over.

A registered podiatrist confirmed diagnosis when the pedal wart exhibited both the characteristic pinpoint bleeding with debridement and pain on lateral compression.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants were excluded from the study if they were prone to impaired healing (peripheral vascular disease, keloid scarring, anticoagulant therapy, haemophilia); were immunosuppressed or taking immunosuppressant drugs; were pregnant during the treatment period; had any previous adverse reactions to local anaesthetics; had suspected bacterial infection at the treatment site; were unable to give informed consent; were currently in a trial evaluating other treatments for their wart/s; were intending to treat their wart/s by other means during the trial period; had a primary pedal wart that was larger than 20mm in diameter; were receiving renal dialysis; had neuropathy; or were otherwise deemed not fit for treatment.

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 is not concealed"
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation to receive either needling or LNC was performed by a member of the research team using a 'randometer' in Microsoft Office Excel. This 'randometer' allocated participants to either needling or LNC with 50:50 odds.

The randomisation procedure occurred after the participant gave informed consent to treatment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analysis was conducted with IBM SPSS Statistics version 20 with the significance level set at 0.05 for all outcome measures. The fisher’s exact test was used for the primary outcome and secondary outcomes: ‘regression of satellite pedal warts’ and ‘complete pedal wart regression’. The ‘cosmetic outcome of the primary pedal wart’ outcome data was analysed with the Mann-Whitney U test. The participant pain, satisfaction levels and participant opinion of cosmesis outcomes were analysed using descriptive statistics. Adverse events from treatment were documented on a case-by-case basis.

Recruitment
Recruitment status
Completed
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)
WA
Recruitment postcode(s) [1] 6178 0
6009 - Crawley

Funding & Sponsors
Funding source category [1] 286564 0
University
Name [1] 286564 0
University of Western Australia
Address [1] 286564 0
35 Stirling Highway, Crawley WA 6009
Country [1] 286564 0
Australia
Primary sponsor type
Individual
Name
Professor Reza Naraghi
Address
Podiatry Department (Park Avenue Building)
35 Stirling Highway, Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 285349 0
None
Name [1] 285349 0
Address [1] 285349 0
Country [1] 285349 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288631 0
University of Western AUstralia Human Research Ethics Committee
Ethics committee address [1] 288631 0
35 Stirling Highway, Crawley WA 6009
Ethics committee country [1] 288631 0
Australia
Date submitted for ethics approval [1] 288631 0
Approval date [1] 288631 0
16/05/2012
Ethics approval number [1] 288631 0
RA/4/1/5336

Summary
Brief summary
Background: The armamentarium for cutaneous warts is vast, the majority of which are not supported by high quality, randomised, controlled trials. We hypothesised that needling of a pedal wart would create local inflammation and a subsequent cell-mediated immune response against human papillomavirus. The primary objective of this study was to investigate if needling to induce cell-mediated immunity against human papillomavirus is an effective treatment of pedal warts in comparison to liquid nitrogen cryotherapy. A secondary objective of this study was to investigate if the cell-mediated immune response induced by needling is effective against satellite pedal warts.

Methods: Eligible participants presenting to the University of Western Australia Podiatry Clinic with pedal wart/s were randomly allocated to treatment — either needling or nitrogen cryotherapy. Only the primary pedal wart was treated during the study. The participants were followed over a twelve-week period with outcome assessments made independently under blinded circumstances.

Results: Thirty-seven participants were enrolled in the study with 18 allocated to needling and 19 to liquid nitrogen cryotherapy. Regression of the primary pedal wart occurred in 64.7% (11/17) of the needling group and 6.2% (1/16) of the liquid nitrogen cryotherapy group (p=0.001). There was no significant evidence to suggest needling of the primary pedal wart will result in regression of one or more satellite pedal warts (p=0.615) or complete pedal wart regression (p=0.175). There was no significant difference in pain, satisfaction or cosmesis between the two groups.

Conclusions: The regression rate or the primary pedal wart is significantly higher in the needling group compared to the liquid nitrogen cryotherapy group. There is no significant evidence that needling of the primary pedal wart to induce a cell-mediated immune response is effective against satellite pedal warts.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37050 0
Mr DANIEL CUNNINGHAM
Address 37050 0
50 Breaksea Drive, North Coogee, Western Australia, 6163
Country 37050 0
Australia
Phone 37050 0
+61406589828
Fax 37050 0
Email 37050 0
cunnid01@gmail.com
Contact person for public queries
Name 37051 0
Mr DANIEL CUNNINGHAM
Address 37051 0
50 Breaksea Drive, North Coogee, Western Australia 6163
Country 37051 0
Australia
Phone 37051 0
+61406589828
Fax 37051 0
Email 37051 0
cunnid01@gmail.com
Contact person for scientific queries
Name 37052 0
Mr DANIEL CUNNINGHAM
Address 37052 0
50 Breaksea Drive, North Coogee, Western Australia, 6163
Country 37052 0
Australia
Phone 37052 0
+61406589828
Fax 37052 0
Email 37052 0
cunnid01@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary