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Trial registered on ANZCTR


Registration number
ACTRN12618002038279
Ethics application status
Approved
Date submitted
12/12/2018
Date registered
20/12/2018
Date last updated
20/12/2018
Date data sharing statement initially provided
20/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised, double-blind, placebo-controlled study of the, efficacy and safety metronidazole ointment in facilitating resolution of non-healing pilonidal sinus
Scientific title
Randomised, double-blind, placebo-controlled study of the, efficacy and safety metronidazole ointment in facilitating resolution of non-healing pilonidal sinus
Secondary ID [1] 296868 0
CT-2017-CTN-05016-1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pilonidal disease 310782 0
Chronic wound 310783 0
Condition category
Condition code
Skin 309462 309462 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment Group A: Metronidazole 10% w/w ointment.
A 2.5 cm strip of ointment (approximately 700 mg) will be administered topically to the wound together with suitable dressing, once daily for 6 weeks unless 100% healed earlier.
One dose contains approximately 70 mg metronidazole in a formulation of white soft paraffin. The investigator will demonstrate to the subject how to apply a 2.5 cm of ointment and dress the wound by applying the first dose and covering with a dry, gauze dressing which is to be retained with tape. Larger wounds may require additional amount of ointment to ensure sufficient cover of the wound. Tubes of ointment will be weighed at each visit to measure dosage administered.
Treatment Group B: Metronidazole 20% w/w ointment.
A 2.5 cm strip of ointment (approximately 700 mg) will be administered topically to the wound together with suitable dressing, once daily once daily for 6 weeks unless 100% healed earlier.
One dose contains approximately 140 mg metronidazole in a formulation of white soft paraffin. The investigator will demonstrate to the subject how to apply a 2.5 cm of ointment and dress the wound by applying the first dose and covering with a dry, gauze dressing which is to be retained with tape. Larger wounds may require additional amount of ointment to ensure sufficient cover of the wound.
Tubes of ointment will be weighed at each visit to measure dosage administered.

Intervention code [1] 313143 0
Treatment: Drugs
Comparator / control treatment
Treatment Group C: Placebo ointment.
A 2.5 cm strip of ointment (approximately 700 mg) will be administered topically to the wound together with suitable dressing, once daily once daily for 6 weeks unless 100% healed earlier.
One dose of placebo ointment contains titanium dioxide and white soft paraffin. The investigator will demonstrate to the subject how to apply a 2.5 cm of ointment and dress the wound by applying the first dose and covering with a dry, gauze dressing which is to be retained with tape. Larger wounds may require additional amount of ointment to ensure sufficient cover of the wound.
Tubes of ointment will be weighed at each visit to measure ointment used.

Control group
Placebo

Outcomes
Primary outcome [1] 308425 0
Proportion of patients with healing at 6 weeks
Measured using PUSH score and defined by a PUSH score = 0 .
Timepoint [1] 308425 0
Assessed at 2,4 and the primary timepoint which is 6 weeks after commencement of intervention
Primary outcome [2] 308426 0
Safety.
This will be assessed by the number and proportion of patients with treatment related AEs (as classified by the MeDRA) in all randomised patients receiving at least one dose.

Timepoint [2] 308426 0
2, 4 and 6 weeks after commencement of treatment / placebo
Secondary outcome [1] 354928 0
The rate of wound healing in participants
Measured by using Puritan (TM) wound measuring probe ( wound length at 12 o'clock to 6 o'clock; max width and maximum depth) and calculated using = (baseline mm^3 - current mm^3 ) / baseline mm^3 x 100%

Timepoint [1] 354928 0
2,4,&6 weeks after commencement of intervention
Secondary outcome [2] 354932 0
Patient’s global impression of improvement
Measured by Patient’s Global Impression of Improvement score (PGI-I)

Timepoint [2] 354932 0
2,4,and 6 weeks after commencement of the intervention
Secondary outcome [3] 355002 0
The amount of metronidazole / placebo used.
Change in weight of tubes at baseline (measured in grams) by electronic scales and timepoints
Timepoint [3] 355002 0
2,4,and 6 weeks after commencement of the the intervention
Secondary outcome [4] 355003 0
Change in PUSH score
Measured by delta baseline PUSH and timepoints
Timepoint [4] 355003 0
2,4 and 6 weeks after commencement of the the intervention

Eligibility
Key inclusion criteria
1. Must give written informed consent.
2. Male or female aged greater than or equal to 16 years.
3. Previous surgery for pilonidal disease and failure of healing for more than 6 weeks post-surgical excision of the pilonidal cyst/sinus;
4. Willingness to stop all other concomitant topical preparations at the site of pilonidal disease.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of non-drained abscess (abscess must have been drained more than 6 weeks prior to entry).
2. Patients who are due to undergo surgery related to pilonidal sinus.
3. Previous (in the last 2 weeks) or current treatment with any antibiotic based on medical history prior to screening.
4. Previous treatment with topical metronidazole for pilonidal sinus.
5. Known allergic reaction to metronidazole.
6. Known allergic reaction to excipients of IMP and placebo.
7. Subject is taking any prohibited medication (warfarin-type anticoagulants, fluorouracil, glucocorticoids, other topical preparations to the area of the wound, lithium, cyclosporin and disulfiram).
8. Experimental agents must have been discontinued at least 8 weeks prior to screening for a period equivalent to 5 half-lives of the agent (whichever is longer).
9. History of epilepsy or seizures.
10. Subject has hepatic insufficiency as defined by laboratory values outside the normal ranges.
11. Women who are pregnant or breastfeeding at baseline.
12. Subject with concurrent disease considered by the investigator to be clinically significant in the context of the study.
13. Patients who have clinically significant abnormalities on their screening blood tests. “Clinically significant” will be determined by the surgeon at the study site.
14. Patients who will be unavailable for the duration of the trial, deemed unable to comply with the requirements of the study protocol, likely to be noncompliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason.



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)
The randomisation and allocation of treatment will be controlled by an independent person who has no other involvement in the study and works in hospital pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients compliant with the inclusion and exclusion criteria will be randomised using a simple computer generated model. There is no stratification prior to randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
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
Proportion of patients with complete healing and with partial healing will be presented using point estimates with 95% confidence intervals.
Differences in the rates of healing will be determined by difference in the mean. SE of the mean and 95% confidence interval will be reported.
Time to response will be presented in Kaplan-Meier curves.
PUSH score will be presented by using point estimates with 95% confidence intervals. Comparisons between each treatment and placebo will be based on an Analysis of covariance (ANCOVA) model.
PGI-I will be presented by category using point estimates with 95% confidence intervals. Comparisons between each treatment and placebo will be based on a proportional odds model.
AEs will be classified into standard terminology using a coding thesaurus (MedDRA). Treatment-related AEs will be summarised separately from all AEs. In addition, the maximum intensity of AEs will be summarised. For AEs these will be summarized using descriptive statistics. Results of laboratory tests and measures of vital signs will be presented as summary statistics and as shift tables.
Missing data will be handled using a worst observation carried forward (WOCF) imputation. Sensitivity analyses will be included in the SAP.

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 in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 12713 0
St George Hospital - Kogarah
Recruitment hospital [2] 12714 0
Logan Hospital - Meadowbrook
Recruitment hospital [3] 12716 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 25138 0
2217 - Kogarah
Recruitment postcode(s) [2] 25139 0
4131 - Meadowbrook
Recruitment postcode(s) [3] 25141 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 301437 0
Hospital
Name [1] 301437 0
St George Hospital Colorectal Research Fund
Address [1] 301437 0
C/- Prof David Lubowski
St George Hospital
Gray Street
KOGARAH NSW 2217
Country [1] 301437 0
Australia
Primary sponsor type
Individual
Name
David Lubowski
Address
Hurstville Private Hospital
37 Gloucester Rd
Hurstville NSW 2220
Country
Australia
Secondary sponsor category [1] 301124 0
None
Name [1] 301124 0
Address [1] 301124 0
Country [1] 301124 0
Other collaborator category [1] 280467 0
Commercial sector/Industry
Name [1] 280467 0
SLA PHARMA
Address [1] 280467 0
Ground Floor, Building 6
Leavesden Park
Hercules Way
WD25 7GS
United Kingdom
Country [1] 280467 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302171 0
South Eastern Sydney Local Heal District Human Research Ethics Committee
Ethics committee address [1] 302171 0
Edmund Blacket Building
Prince of Wales Hospital
Randwick NSW 2031
Ethics committee country [1] 302171 0
Australia
Date submitted for ethics approval [1] 302171 0
13/12/2017
Approval date [1] 302171 0
27/02/2018
Ethics approval number [1] 302171 0
17/358 (HREC 18/POWH/86)

Summary
Brief summary
This is a randomised, doubleblind, placebo controlled, multicenter study to be conducted across Australia, with an expected study duration of 8 weeks to determine the safety and efficacy of metronidazole ointment.
Primary Objective
• To determine whether treatment with metronidazole ointment increases healing in subjects presenting with non healing pilonidal disease.
Method
Patients with non healing pilonoidal sinus wounds will be randomised to one of two treatments or placebo. The wound healing will be measured using percentage improvement in wound size(rate of healing), "PUSH" score and time to healing recorded.
Hypothesis
Metronidazole ointment increases healing in subjects presenting with non healing pilonidal disease when compared to placebo.
The research is a medical / clinical research project which studies the efficacy and safety metronidazole ointment in facilitating resolution of non healing pilonidal sinus.The study design is double blind placebo controlled, randomised control trial.
Trial website
N/A
Trial related presentations / publications
Public notes
SLA Pharma are providing in kind support by supplying medication for the trial.

Contacts
Principal investigator
Name 89366 0
Prof David Lubowski
Address 89366 0
Hurstville Private Hospital
37 Gloucester Road
Hurstville NSW 2220
Country 89366 0
Australia
Phone 89366 0
+61 2 85661000
Fax 89366 0
Email 89366 0
davidlubowski@sydneycolorectal.com.au
Contact person for public queries
Name 89367 0
Dr Vicki Patton
Address 89367 0
Level 4 Building 21
Edith Cowan University
Joondalup Drive
Joondalup WA 6027
Country 89367 0
Australia
Phone 89367 0
+61 425266018
Fax 89367 0
Email 89367 0
vickip04@gmail.com
Contact person for scientific queries
Name 89368 0
Dr Vicki Patton
Address 89368 0
Level 4 Building 21
Edith Cowan University
Joondalup Drive
Joondalup WA 6027
Country 89368 0
Australia
Phone 89368 0
+61 425266018
Fax 89368 0
Email 89368 0
vickip04@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Results will be reported collectively and not individually.
What supporting documents are/will be available?
No other documents available
Summary results
No Results