Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000520437
Ethics application status
Approved
Date submitted
14/04/2016
Date registered
21/04/2016
Date last updated
9/03/2021
Date data sharing statement initially provided
19/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of glyceryl trinitrate ointment as treatment for leg ulcers
Scientific title
A double blind (pilot) trial of the application of 0.2% glyceryl trinitrate ointment for the healing of chronic venous leg ulcers.
Secondary ID [1] 284174 0
Trial Number:2014/0114 CTN Scheme (Drugs)
Schedule 5A of Regulation 12 of the Therapeutic Goods Administration
Universal Trial Number (UTN)
U1111-1153-9849
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic venous leg ulcers 291270 0
Condition category
Condition code
Cardiovascular 291622 291622 0 0
Diseases of the vasculature and circulation including the lymphatic system
Skin 291623 291623 0 0
Other skin conditions
Inflammatory and Immune System 291624 291624 0 0
Connective tissue diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The proposed research plans to examine the application of an ointment containing glyceryl trinitrate (GTN) [Rectogesic 0.2% GTN], a pharmaceutical agent approved for human use, on venous leg ulcers. GTN ointment works in part by releasing nitric oxide (NO) into the wound, which acts to improve blood flow to the area and has the capacity to kill unwanted bacteria in the wound. The product to date has not been used routinely for the treatment of venous leg ulcers. A previous study by the chief investigator demonstrated the enzyme (iNOS), which drives the production of NO, was elevated in patients with faster healing leg ulcers, suggesting that application of a topical GTN donor (the ointment) might accelerate this healing process.
The trial will be double blinded with half of the recruited patients (n=20) receiving a placebo ointment and the other half receiving the GTN donor ointment (n=20). Neither the patients nor the research nurse involved in treatment will know if the product used is the placebo or the GTN donor ointment. Participants will receive 4 x weekly dressings (weekly for 4 weeks) for the ulcer, which will include an application of the randomised ointment (5-10mL depending on the size of the ulcer) and standardised usual care (e.g. compression bandaging or similar) as prescribed. All dressings will be undertaken by the research nurse in the hospital setting, with participants as inpatients in a hospital ward, or if discharged, as outpatients in a home or clinic setting. Participants will be referred to their GP for usual treatment at the completion of the 4 weekly treatments if their ulcer is not healed.

Rates of healing will be determined by planimetry (ulcer tracing) using computer software for the purpose (Pictzar) since complete healing of the ulcer will most likely not be achieved in the time frame being examined. If a statistically significant difference exists between the two groups the treatment will deemed successful. It is hoped that a subsequent larger trial will be planned based on the findings from this study.
Intervention code [1] 288872 0
Treatment: Drugs
Comparator / control treatment
Placebo ointment is the base ointment that is identical to the intervention ointment without the active ingredient (glyceryl trinitrate).
Control group
Placebo

Outcomes
Primary outcome [1] 291558 0
The trial will run only for 4 weeks so rates of healing will be determined by planimetry (ulcer tracing) using computer software for this purpose (PicZar).Complete healing of the ulcer will most likely not be achieved in the time frame being examined. If a statistically significant difference exists between the two groups the treatment will deemed successful. It is hoped that a subsequent larger trial will be planned based on the findings from this pilot clinical trial. The trial is therefore a "proof of concept" trial before larger Phase 2 trials begin.
Timepoint [1] 291558 0
Four weeks after treatment (i.e. Each participant will be treated weekly for 4 weeks).
Secondary outcome [1] 307073 0
Nil
Timepoint [1] 307073 0
Nil

Eligibility
Key inclusion criteria
transdermal oxygen sensors will not be used. Clinical judgement will be used.
This investigation seeks to recruit consenting patients with venous leg ulceration from the internal medicine wards of the Prince Charles Hospital (TPCH). Venous ulceration will be confirmed by clinical judgement and patient notes and/or confirmation by medical and/or podiatry team. This is to rule out ulceration by other aetiologies (i.e. arterial, pressure, diabetic) which have been shown in earlier studies to not benefit from GTN application (data not published).

Patients recruited into this study will be informed that their participation in this trial is entirely voluntary and no financial payment will be given. If patients decide to not take part in this study, there will be no prejudice against their future care and are free to withdraw at any time. Consenting patients will then be randomly allocated to one of two groups (placebo versus GTN treatment).
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients must have venous ulceration. Additionally, patients with malignant ulcers or have other forms of malignancy will be excluded from the study together with any patient who has active autoimmune disease or have had organ transplantation. Patients with acute exacerbation of cardiac disease may be excluded from treatment with GTN as the product may lower blood pressure. Those with ongoing / active cardiac disease will be included.

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)
A set of 40 opaque sealed envelopes will be prepared according to the randomisation allocation list described in sequence generation. Only one researcher will have access to the randomisation list and will prepare the envelopes. All patients who meet the inclusion criteria will be asked by the research nurse to participate in the study. Once a patient consents to participate, the next envelope in the numerical sequence will be opened and the product with the corresponding number will be used for treatment for that participant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A random number generator will be used to randomise control (placebo) and experiment (GTN) allocation 1:1 across a set of numbers from 1 - 40 (40 patients in study). A set of numbered labels for 40 bottles of product (20 GTN and 20 placebo) will be prepared using the randomised allocation. Only one researcher will label the products with numbers according to the prepared randomisation list. All other researchers involved in preparation of product and data collection and analysis processes will be blinded 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 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a pilot study so size of sample for power for this phenomenon is not known. A previous related study has shown some effect in a very small sample size.
The primary outcome measure is rate of healing.
Data will be entered manually into the most recent version of SPSS for analysis. Descriptive statistics will be used to summarise the data e.g. means and percentages. Parametric tests (provided data assumptions are met) will be used to analyse differences and relationships between variables. Significance will be set at p < 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/11/2016
Actual
10/12/2016
Date of last participant enrolment
Anticipated
31/03/2021
Actual
Date of last data collection
Anticipated
30/04/2021
Actual
Sample size
Target
40
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 5596 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 13047 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 293342 0
University
Name [1] 293342 0
Australian Catholic University
Country [1] 293342 0
Australia
Funding source category [2] 297348 0
Commercial sector/Industry
Name [2] 297348 0
Care Pharmaceuticals
Country [2] 297348 0
Australia
Funding source category [3] 297349 0
Commercial sector/Industry
Name [3] 297349 0
3M Australia Pty. Limited
Country [3] 297349 0
Australia
Funding source category [4] 297350 0
Commercial sector/Industry
Name [4] 297350 0
Radiometer Pacific
Country [4] 297350 0
Australia
Primary sponsor type
Hospital
Name
The Prince Charles Hospital
Address
Rode Road
Chermside QLD 4032
Country
Australia
Secondary sponsor category [1] 292161 0
University
Name [1] 292161 0
Australian Catholic University
Address [1] 292161 0
40 Edward St
North Sydney NSW 2060
Country [1] 292161 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294832 0
Human Research Ethics Committee Metro North Hospital and Health Services, The Prince Charles Hospital
Ethics committee address [1] 294832 0
Research Ethics and Governance Office
Building 14
Rode Road
Chermside QLD 4032
Ethics committee country [1] 294832 0
Australia
Date submitted for ethics approval [1] 294832 0
04/04/2013
Approval date [1] 294832 0
29/04/2013
Ethics approval number [1] 294832 0
HREC/13/QPCH/68

Summary
Brief summary
The proposed research plans to examine the application of an ointment (Rectogesic 0.2% GTN), a pharmaceutical agent approved for human use, on venous leg ulcers. GTN ointment works in part by releasing nitric oxide (NO) into the wound, which acts to improve blood flow to the area and has the capacity to kill unwanted bacteria in the wound. The product to date has not been used routinely for the treatment of venous leg ulcers. A previous study by the chief investigator demonstrated the enzyme (iNOS), which drives the production of NO, was elevated in patients with faster healing leg ulcers, suggesting that application of a topical GTN donor (the ointment) might accelerate this healing process.

The trial will be double blinded with half of the recruited patients receiving a placebo and the other half receiving the GTN donor. Neither the patients nor the research nurse involved in treatment will know if the product is the placebo or the GTN donor. The trial will run only for 4 weeks for each patient so rates of healing will be determined by planimetry (ulcer tracing) as complete healing of the ulcer will most likely not be achieved in the time frame being examined. If a statistically significant difference exists between the two groups the treatment will deemed successful. It is hoped that a subsequent larger trial will be planned based on the findings from this study.

Hypothesis:
Participants receiving the Rectogesic (GTN donor) will have a statistically higher linear healing rate (LHR) compared to patients that receive only the placebo.
Trial website
none
Trial related presentations / publications
Public notes
none
Attachments [1] 837 837 0 0
/AnzctrAttachments/365884-Research_Protocol_GTNlegulcertrial_Version_2_170715_finalised.doc

Contacts
Principal investigator
Name 46594 0
Dr Roger Lord
Address 46594 0
School of Science, Brisbane
Australian Catholic University
1100 Nudgee Road
Banyo QLD 4014
Country 46594 0
Australia
Phone 46594 0
+61 7 3623 7240
Fax 46594 0
+61 7 3623 7242
Email 46594 0
roger.lord@acu.edu.au
Contact person for public queries
Name 46595 0
Damian Williams
Address 46595 0
The Prince Charles Hospital
Rode Road
Chermside QLD 4032
Country 46595 0
Australia
Phone 46595 0
+61 7 3139 5646
Fax 46595 0
Email 46595 0
Damian.Williams@health.qld.gov.au
Contact person for scientific queries
Name 46596 0
Roger Lord
Address 46596 0
School of Science, Brisbane
Australian Catholic University
1100 Nudgee Road
Banyo QLD 4014
Country 46596 0
Australia
Phone 46596 0
+61 7 3623 7240
Fax 46596 0
Email 46596 0
roger.lord@acu.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
Only aggregated data is available


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.