Pilot Study Comparing NatroxTM Topical Oxygen Therapy to A Placebo in the Management of Non-Healing Leg Ulcers

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness of the NatroxTM Topical Oxygen device versus a placebo in patients with non-healing leg ulceration in conjunction with standard best practice.

Detailed Description
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Patients will be screened for two weeks before enrollment to assess whether their ulcers are non-healing, defined as a reduction in wound surface of < 25% after two weeks of standard best practice wound care . On enrolment and randomisation to active or placebo treatment the patient will be treated for six weeks or until 100% epithelialisation, whichever is the sooner, and then treatment will revert to standard best practice, defined as moist wound healing plus compression where appropriate. The reference ulcer will be followed up at two weeks and then at six weeks after the end of the active treatment period.

Official Title
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A Randomised Controlled Double Blind Pilot Study Comparing NatroxTM Topical Oxygen Therapy to A Placebo in the Management of Non-Healing Leg Ulcers in Conjunction With Standard Best Practice

Conditions
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Skin Ulcer Venous Stasis Chronic, Mixed Arteriovenous Leg Ulcer

Intervention / Treatment
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* Device: NatroxTM Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with superficial venous and mixed aetiology leg ulcers on a flat plane in surface area between 4-50cm2 Patients with diabetes may be included providing they have good metabolic control Patients who understand the trial, agree to adhere to the treatment and are able to give consent Patients who can be followed by the same investigating team for the whole period of their participation in the study Exclusion Criteria: Patients who present with wounds which are clinically infected and require antimicrobial therapy. Patients who have been treated for a wound infection with antimicrobial therapy (systematically or topically) may be included providing the wound is no longer assessed as infected and there is a two week wash-out period after the last treatment before the patient is reassessed against the inclusion and exclusion criteria Patients with a known sensitivity to any of the components of the evaluation device Patients with known or suspected malignancy in the wound or surrounding tissue Patients whose wounds show a percentage decrease in surface area of >25% during the two week screening period Patients who do not have the physical or mental capacity, or a significant other with the ability to change the NatroxTM battery pack on a daily basis Patients who present with more than 10% of the wound surface area covered in hard eschar Patients who are actively treated with immunosuppressive or cortico-steroidal medication Patients who are participating in another clinical trial Patients with a known history or poor compliance with medical treatment Patients who have been in this trial previously and have withdrawn Patients who are unable to understand the aims of the trial and do not give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo device<br>The placebo comparator is a placebo version of the active device which is a system to deliver oxygen from an oxygen generator topically to the wound bed via a proprietary device. The device will be applied to the wound and attached to the placebo oxygen generator and the generator switched on at the time of enrolment. Secondary dressings will then be applied. The device will be removed and reapplied at each dressing change for a treatment period of 6 weeks. | Device: NatroxTM Device<br>* The NatroxTM device is a system to deliver oxygen from an oxygen generator topically to the wound via a proprietary device. The NatroxTM ODS oxygen delivery device will be applied to the wound and attached to the oxygen generator and switched on at the time of first dressing application at enrolment. Secondary dressings will then be applied. The oxygen delivery device will be removed and reapplied at each dressing change for a treatment period of 6 weeks.<br>* Other names: NatroxTM Oxygen Generator;|
| Active Comparator: NatroxTM Device<br>A system to deliver oxygen from an oxygen generator topically to the wound via a proprietary device. The NatroxTM oxygen delivery device will be applied to the wound and attached to the NatroxTM oxygen generator which will be switched on at the time of first dressing application at enrolment. Secondary dressings will then be applied. The device will be removed and reapplied at each dressing change for a treatment period of 6 weeks. | Device: NatroxTM Device<br>* The NatroxTM device is a system to deliver oxygen from an oxygen generator topically to the wound via a proprietary device. The NatroxTM ODS oxygen delivery device will be applied to the wound and attached to the oxygen generator and switched on at the time of first dressing application at enrolment. Secondary dressings will then be applied. The oxygen delivery device will be removed and reapplied at each dressing change for a treatment period of 6 weeks.<br>* Other names: NatroxTM Oxygen Generator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of the NatroxTM Topical Oxygen Device | Effectiveness of the NatroxTM Topical Oxygen Device will be established vs. Placebo in patients with non-healing leg ulceration in conjunction with best practice. Effectiveness will measured by the absolute and relative change in wound surface area as measured by digital photography and wound-mapping software. | Baseline at week 0 and then at 6 and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the wound pain over the study duration | Measured using a validated Visual Analogue Scale ranging from 0 to 10 | Baseline at week 0, and then each weekly dressing change, 8 weeks and 12 weeks | 
| Patient comfort with the device at dressing change | Patient will be recorded on each visit with the dressing applied and will be recorded as a yes/no to comfort experienced by the patients | first removal of device and then on subsequent weekly changes | 
| Patient acceptability of the device during wear | Patient questioned as to ability to mobilise, comfort of dressing and device and possible disturbance of sleep patterns, answers recorded as yes/no | Each weekly dressing change until week 6 | 
| Statistical information from which to power a future large multi-centre randomised trial | Statistical information on use of Natrox device and effectiveness on patients. Wound surface area will be measured in square centimetres as defined by wound mapping software. The wound surface area reduction between six weeks and baseline will then be calculated. Wound surface area will be measured at weekly intervals for the 6 weeks of active treatment and then at weeks 8 and 12 for follow up. The primary analysis will be an intent-to-treat analysis. A two-sided significance level of 0.05 will be used for all analyses. A general linear model taking into account the treatment groups and centres (surgical and dermatology clinics) as fixed effects and a baseline wound surface area as a covariate will be used to test the null hypothesis of similar effects in surface area reduction between treatment groups. | Study End at week 12 | 
| Efficiency of Exudate transportation through the device to the secondary dressing | Measured by the frequency of changes of the secondary dressing and by recording the incidence of maceration. | weekly up to week 6 (end of natrox treatment period) | 
| Improvement in the wound bed during treatment with Natrox and Oxygen Delivery System (ODS) | Measured by visual assessment weekly by the Investigators | Baseline at week zero, weekly and end of treatment at week 6 | 
| Reliability of the protocol | The reliability of the protocol will be determined by ability to implement it in the clinical setting effectively and the accuracy of the outcomes delivered from the study | Study end follow up at week 12 | 
| Monitor the safety of the device in use | Measured by recording the incidence and severity of adverse events as reported. | Study treatment end at week 6 and then until follow up at 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venous leg ulcer, mixed aetiology leg ulcers