Evaluation of glyceryl trinitrate ointment as treatment for leg ulcers

INTERVENTION: 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 of compression bandaging with foam dressing as needed. 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 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. CONDITION: Chronic venous leg ulcers PRIMARY OUTCOME: 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. SECONDARY OUTCOME: Nil INCLUSION CRITERIA: 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 the use of transdermal oxygen sensors in conjunction with equipment provided by Podiatry (TPCH). 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).