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

September 23, 2021 updated by: Singapore General Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects with non-healing Diabetic Foot Ulcers that has been persistent for more than 3 months, or less than 50% healing observed within 1 month for amputation sites.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
>40% wound area reduction after 1 month
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
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
A small battery-powered electrochemical "oxygen generator" to concentrate atmospheric oxygen and feed to wound site through a dressing-like "oxygen distribution system"

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage change in ulcer size
Time Frame: 12 weeks after NATROX™ fitted
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
Time Frame: 16 weeks after last patient enrolled
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
Time Frame: 16 weeks after last patient enrolled
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
Time Frame: 16 weeks after enrolment
16 weeks after enrolment
Number of infection episodes
Time Frame: 16 weeks after enrolment
16 weeks after enrolment
Diabetic Foot Ulcer Scale
Time Frame: Baseline (week 0), Week 4, Week 8, Week 12 and Week 16 post enrolment
To assess quality of life
Baseline (week 0), Week 4, Week 8, Week 12 and Week 16 post enrolment
Pain at wound site
Time Frame: Baseline (week 0), Week 4, Week 8, Week 12 and Week 16 post enrolment
Assessed using a visual analogue scale
Baseline (week 0), Week 4, Week 8, Week 12 and Week 16 post enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Singapore General Hospital

Investigators

  • Principal Investigator: Tang Tjun Yip, Singapore General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 17, 2018

Primary Completion (Actual)

March 23, 2021

Study Completion (Actual)

May 31, 2021

Study Registration Dates

First Submitted

March 4, 2019

First Submitted That Met QC Criteria

March 4, 2019

First Posted (Actual)

March 5, 2019

Study Record Updates

Last Update Posted (Actual)

September 27, 2021

Last Update Submitted That Met QC Criteria

September 23, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018/2355

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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