An Observational Clinical Trial Examining the Effect of Topical Oxygen Therapy (NATROX™) on the Rates of Healing of Chronic Diabetic Foot Ulcers

Study Overview
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Brief Summary
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This study aims to evaluate the effectiveness of NATROX™ Topical Oxygen Wound Therapy for subjects with non-healing foot ulceration. Subjects will be treated with standard care for 4 weeks. If the wound is not reduced by more than 40%, NATROX™ will be applied for the next 12 weeks. Throughout the study period, wound measurements will be taken to measure wound reduction.

Detailed Description
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Diabetes and its attendant complications are increasing year on year. A number of macro- and micro-circulatory changes occur as a result of long standing or poorly controlled diabetes. These, often in association with either loss of lower limb sensation, or mechanical changes in the foot architecture, can lead to the formation of foot ulcers. These can be hard to heal because of the changes in the diabetic foot described above, as well as an increased incidence of infection in this population. Invasive or ascending infection through these breaks in the skin can lead to tissue loss, which may range from a single toe to major amputation below or above the knee. Major limb amputation has a profound effect on patient's quality of life, as well as a significant economic impact on the health and social care budget. Caring for diabetic foot ulcers, and the complications of this, have a cost of around S$1.2 billion per annum, which has become a focus of public health concern in Singapore recently. The concept of increasing the oxygen concentration in healing wounds developed originally with hyperbaric oxygen therapy, and from the fact that oxygen is one of the most essential elements used during cellular metabolism. Poor tissue oxygenation, as is often seen in diabetic foot ulcers, is a significant impediment to cellular activity, and is therefore very likely to impair wound healing. The NATROX™ topical oxygen therapy system developed by Inotec AMD Limited employs a small battery-powered electrochemical oxygen generator to concentrate atmospheric oxygen and feed the pure, moist, oxygen at a rate of around 13ml/hour through a fine, soft, tube to a dressing-like oxygen distribution system that is placed over the wound and is held in place by a conventional dressing. The oxygen generator is worn in a holster on the waist or above the calf, or is placed in a trouser pocket, thus enabling the patient to enjoy normal mobility (hence ambulatory) while receiving continuous treatment. The very significant costs of treatment of diabetic foot ulcers and the impact of amputations on quality of life and life expectancy, suggest that Natrox™ treatment is likely to be cost effective, a conclusion that was evident from the brief independent health economics study linked to the project. To date, no Asian study looking at whether the device is efficacious in a multi-racial population like Singapore. The vessels in Asians are generally smaller and the micro circulation is generally more diseased than our Caucasian counterparts because of the higher incidence of diabetes. This technology could be ideal for such patients and improve our limb salvage rates. After revascularization and control of infection, there is little alternative if the wound does not heal apart from further wound debridement or major amputation. This study may show us which Diabetic Foot Ulcers or wounds are likely to respond to topical oxygen and what effect it has on the patient per se in terms of pain relief and improvement of quality of life.

Official Title
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An Observational Clinical Trial Examining the Effect of Topical Oxygen Therapy (NATROX™) on the Rates of Healing of Chronic Diabetic Foot Ulcers

Conditions
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Diabetic Foot Ulcer, Non-healing Wound

Intervention / Treatment
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* Device: NATROX™ Topical Oxygen Therapy System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diabetic foot ulcer greater than 12 weeks and less than 18 months in duration Minor amputation sites <50% healed in 4 weeks (the use of negative pressure wound therapy to optimize the wound bed is allowable) 4 weeks of standard of care at the hospital based diabetic foot clinic or in a specialist community diabetic podiatry clinic prior to entry into the open registry No planned revascularization (endovascular or open surgery) within 4 weeks following revascularization being performed) Ongoing active chemical or sharp wound debridement prior to and during the application of NATROX™ No limit on level of ischemia, either high or low. The extent of arterial disease will be documented by angiogram or duplex ultrasound and toe blood pressure The subject is 21 years of age or older The subject is willing to complete >75% of follow-up evaluations required by the study protocol The subject is able to abstain from any other clinical trial for the duration of the study The study is able to read and understand instructions and give voluntary written informed consent The subject is able and willing to follow the protocol requirements Exclusion Criteria: Inability to comply with the dressing regime or manage the NATROX™ device Disseminated malignancy Subjects with a >1 year life expectancy Subjects with an ulcer which is <0.5cm2 or >50cm2 Subjects who is dialysis dependent for less than 1 year (i.e. subject is eligible for study if has CKD/ESRF and is on dialysis for >1year) The subject has an invasive soft tissue infection at the time of baseline assessment, requiring oral or intravenous antibiotic therapy. Exposed bone without soft tissue or granulation tissue across the surface Acute osteomyelitis (stable, chronic osteomyelitis is allowable, including those maintained on oral antibiotics, as long as there is no planned intervention) Pregnant/lactating females (self-reported or tested, as per institutional requirements) Glycated haemoglobin HbA1C of >12mmol mol-1 Subject who have evidence of connective tissue disorders (e.g. vasculitis or rheumatoid arthritis) under active treatment The subject is unable to follow the protocol The subject has other concurrent conditions that in the opinion of the investigator may compromise subject safety The patient is a vulnerable or protected adult The patient is unable to provide informed consent Diabetic foot ulcer is connected to a sinus wound

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| >40% wound area reduction after 1 month<br>Subjects to continue with standard practice for the next 12 weeks, or until the wound has completely healed. | |
| <40% wound area reduction after 1 month<br>Subjects to be fitted with NATROX™ after 1 month, over a period of 12 weeks or until the wound has completely healed. | Device: NATROX™ Topical Oxygen Therapy System<br>* A small battery-powered electrochemical oxygen generator to concentrate atmospheric oxygen and feed to wound site through a dressing-like oxygen distribution system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in ulcer size | after 12 weeks of NATROX™ therapy, relative to baseline measurement | 12 weeks after NATROX™ fitted | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Closure Number | Total number of patients with wounds that completely healed at the end of study period | 16 weeks after last patient enrolled | 
| Wound Closure Rate relative to the 4-week run in period | Number of wounds 100% healed at the end of 4 week run-in | 16 weeks after last patient enrolled | 
| Number of dressing episodes during the study period |  | 16 weeks after enrolment | 
| Number of infection episodes |  | 16 weeks after enrolment | 
| Diabetic Foot Ulcer Scale | To assess quality of life | Baseline (week 0), Week 4, Week 8, Week 12 and Week 16 post enrolment | 
| Pain at wound site | Assessed using a visual analogue scale | Baseline (week 0), Week 4, Week 8, Week 12 and Week 16 post enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Topical Oxygen, Wound Management