Condition category
Skin and Connective Tissue Diseases
Date applied
29/07/2019
Date assigned
11/09/2019
Last edited
11/09/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Diabetic foot ulcers (DFU) can lead to infection and further deterioration to health. They are a considerable burden to both the NHS and the patient. Clinicians have the option to treat the wound conservatively or more aggressively with oxygen. At present there is a lack of data available to aid clinicians in deciding what approach is best. Oxygen has been shown to be essential in wound healing, and extra oxygen supply to a wound may help it to heal quicker. This study will test if this is indeed the case by using a ‘Natrox topical oxygen therapy device’ that supplies extra oxygen directly to foot ulcers. We will also evaluate what patients think of the treatment and monitor for any safety events.
The device would be applied to the wound by the patient’s podiatry team and the patient’s normal dressings will be placed over the top. The patient is asked to wear the device until the wound is healed, or for 12 weeks, whichever comes first. The plastic tubing and ‘web’ that touches the wound will be replaced at regular podiatry appointments (maximum of 7 days apart). About every month, the battery pack may be replaced.
The main aim of the study is see if it is practical to evaluate the Natrox oxygen delivery device as a treatment for foot ulcers. We will also look at how quickly foot wounds heal and compare normal care versus normal care plus Natrox oxygen therapy. We will do this by measuring and taking photos of the wound (six times over 12 weeks).
The study would also like to answer the following questions; how is the device to use (feedback from people using Natrox)? How does having a foot ulcer affect quality of life, and does Natrox affect the presence of any bacteria present in the foot ulcer? We will do this by asking participants to complete some short questionnaires, and by taking some microbiology swabs from the wound.

Who can participate?
Patients with a diabetic foot ulcer being managed by the podiatry service can take part who meet all of the following criteria: who are non-smokers over 18 years of age, where the foot ulcer is at least 6 weeks old, with no active infection in the foot ulcer currently being treated by intravenous antibiotics

What does the study involve?
There are no extra appointments involved in taking part in this study. Any activity relating to the study should take place at the patient’s usual Podiatry appointment. The first 4 weeks of the study are called the ‘screening phase’; if the wound heals by 50% or more than the patient is not eligible for the main ‘trial’ phase and participation ends.
If the foot ulcer heals by less than 50% then the patient will continue into the 12-week trial phase. At the 4-week point, the patient will be randomised to either care as usual or care as usual plus Natrox oxygen therapy. This a one in two chance of being allocated to the Natrox treatment arm of the study. After allocation, you will be followed up for a further 12 weeks, meaning that participation will last 16 weeks in total.

What are the possible benefits and risks of participating?
Participants receiving the Natrox device may benefit from improved foot ulcer healing (compared to usual care). However, although there is some evidence that this is the case, it is not yet proven beyond doubt. This study aims to see how effective the Natrox device is.

Natrox is a licensed medical device, and the product has a CE mark. Risk of a reaction, or increased risk because of the use of Natrox, will be extremely low, because the oxygen flow is relatively low at 15 ml/hour. Because of the strict manufacturing standards, there should be no risk of infection from the medical device itself. However, if a healthcare professional or the research team learn of important new information that might affect the willingness of a participant to remain in the study, they will let the patient know. Also, this study aims to check the safety of using the Natrox device for the treatment of foot ulcers. Appropriate precautions are in place to ensure all medical and personal information is kept safe. The number of visits associated with the study is not any more than the number of visits that would be involved in usual treatment. If the wound heals before the end of the 12-week intervention phase then the patient will be discharged as per normal care.

Where is the study run from?
The study is run by Cumbria Partnership NHS Foundation Trust, through the Community Services and Research Department

When is the study starting and how long is it expected to run for?
The study is recruiting participants from August 2019 until May 2020.

Who is funding the study?
1. Inotec AMD Limited, UK
2. Academic Health Sciences Network

Who is the main contact?
Ms Katie Boichat (Specialist Podiatrist), Chief Investigator for ANODE
research@cumbria.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Leon Jonker

ORCID ID

Contact details

R&D Dept
Carleton Clinic
Carlisle
CA1 3SX
United Kingdom
+441228 608926
leon.jonker@nihr.ac.uk

Type

Public

Additional contact

Ms Katie Boichat

ORCID ID

Contact details

Cumbria Partnership NHS Foundation Trust
Podiatry Dept
Cockermouth Community Hospital
Cockermouth
CA13 9HT
United Kingdom
+441900 324252
katie.boichat@cumbria.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

41693

Study information

Scientific title

Prospective, multicenter, randomised controlled feasibility trial of the application of NATROX® topical oxygen therapy in patients with chronic and delayed healing foot ulcers

Acronym

ANODE

Study hypothesis

ANODE wishes to determine the feasibility of conducting a full RCT in the future, while also assessing the acceptability and effectiveness of the Natrox oxygen device. As such, the study does not lend itself to a hypothesis. However, a future hypothesis would be that chronic and delayed-healing foot ulcers will heal quicker using a “Natrox topical oxygen therapy device” compared to standard care.

Ethics approval

1. Approved 19/07/2019, Health and Care Research Wales (Castle Bridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; HCRW.approvals@wales.nhs.uk; +442920 230457), ref: 19/ES/0073
2. Approved 19/07/2019, East of Scotland Research Ethics Service (Tayside Medical Science Centre, Residency Block Level 3, George Pirie Way, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK; eosres.tayside@nhs.net; +44 1382 383871), ref: DL/19/ES/0073

Study design

Non-randomised; Interventional; Design type: Treatment, Device

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Foot ulcer

Intervention

The NATROX® oxygen wound therapy device is a licensed battery-operated class II medical device, which via a ‘web’ shaped applicator delivers approximately 15 ml of oxygen per hour to the wound.

In this study, twenty patients, recruited from two NHS Trusts, will be enrolled in a real-world evaluation study. Patients will be eligible for NATROX® therapy if, according to standard practice, their wound has not healed by at least 50% in the four weeks prior. Clinical (wound status) and patient-reported outcome measures will be collated at baseline, and periodically up to 12 weeks. The wound-related costs, including staffing, clinics, dressings and diagnostics will be included in this analysis. Since the NATROX® device is already CE-marked, it can be incorporated in standard wound care practice across the UK without the need for regulatory delays and with minimal need for staff training. However, this is provided NATROX® proves to be effective, safe, and cost-effective.

If patients decide to take part in the study, one of the research staff, which may be the regular podiatrist, will take written consent. Once written informed consent has been obtained, they will enter the 4-week long screening phase (week -4 to 0).
After the first four weeks, they will either qualify for randomisation and 12-week intervention phase (if healing is less than 50% in screening phase) or they complete the study (if the wound heals 50% or more in screening phase).

Those who are randomised are allocated to either:
- treatment as usual (control) arm
- treatment as usual plus Natrox oxygen therapy arm

Then they will all start the trial phase, which lasts 12 weeks, but there will be no change to how many times they see their podiatrist and where they see them. The research visits that coincide with podiatry appointments are:
- Week -4. Informed consent. Ulcer size and wound characteristics/baseline clinical information
- Week 0. Collection of Ulcer size and wound characteristics plus patient questionnaires (quality of life, wound impact), microbiology swabs.
- Week 3, 6 , 9, 12, Research follow-up visit (at same time as regular visits to podiatry), measurement of wound (all visits), swab of wound for microbiology testing , quality of life and wound-related pain (week 0, 6, 12 only), and patient experience questionnaire (week 12 only, or when wound has healed).

Intervention type

Device

Phase

Drug names

Primary outcome measure

1. Natrox arm only: Participants’ experience of and compliance with Natrox oxygen therapy is measured using a bespoke questionnaire at 12 weeks.

Assessed at the end of the study:
2. Recruitment and attrition rates, willingness of patients to consent and to be randomised, response rates to questionnaires, and degrees of missing data
3. Testing of eligibility criteria and ability/willingness of clinical staff to partake in recruitment and follow-up of participants
4. Adequacy of duration of follow-up (e.g. in relation to foot ulcer healing) as measured by the number of appointments made for and attended by the patient relating to the foot ulcer
5. Appropriateness of inclusion/exclusion criteria and outcomes measures (both clinical and patient-reported)

Secondary outcome measures

1. Clinical characterisation of the wound -- including clinical opinion of infection (none, possible, infected), erythema (none, slight, significant), purulence (none, slight, significant), and odour (none, low, moderate, high) – is completed at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
2. Ulcer size is measured by Coloplast grid or suitable equivalent at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
3. Ulcer severity is measured by the Pressure Ulcer Scale for Healing (PUSH) at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
4. DFU ulcers only: diabetic ulcer severity is measured by the Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) classification system at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
5. Wound closure status in terms of healed, not healed, or recurrence is recorded at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
6. Pain is measured using the visual analogue score (VAS) at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
7. Quality of life is measured using two tools -- the Cardiff Wound Impact Questionnaire (CWIQ) and the EQ-5D-5L -- at baseline, 6, and 12 weeks
8. Wound swabs are taken and processed to determine culture (bacterial growth and species identification) and antibiotic sensitivity at the start of the screening period (-4 weeks), baseline, 3, 6, 9, and 12 weeks
9. Safety of applied oxygen therapy in comparison to standard care arm is an ongoing outcome measure, and is quantified by wound infection incidence and need for secondary interventions, such as surgery

Overall trial start date

01/05/2019

Overall trial end date

01/10/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Clinical diagnosis of a Foot Ulcer, present on area that is measurable with a grid sheet (this can include plantar, calcaneus, dorsal, hallux, apex, or ankle based ulcers). This includes DFU, peripheral arterial disease related wound, or other aetiology
2. No minimum chronicity applicable for the index foot ulcer
3. Adult patients aged > = 18 years
4. Patients with recurrent wounds, including multiple wounds, are eligible. The largest of the wounds, that is measurable with a grid sheet, will be selected for the trial
5. Mental capacity to give consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 24; UK Sample Size: 24

Participant exclusion criteria

1. Limited life expectancy, i.e. undergoing palliative care
2. Active infection in foot ulcer that cannot be managed in podiatry service (ie requires specialist secondary care intervention)
3. Ulcer penetrating the tendon, periosteum or bone.
4. Foot ulcer in area of the foot, e.g. in between toes, which would make exact ulcer size measurement, or application of the Natrox device, impossible.
5. Pregnant, actively planning to become pregnant, or lactating (all self-reported)
6. Currently receiving intravenous antibiotics, or within one week of receiving iv antibiotics (topical and oral antibiotics are not an exclusion criterion).
7. Participating in another research study involving an investigational product that is related to the DFU or a co-morbidity that may influence wound healing (incl diabetes, peripheral arterial disease, or immune disorders).
8. Concurrent (medical) conditions that in the opinion of the investigator may compromise patient safety or study objectives, or significantly impede compliance with NATROX® therapy.

Recruitment start date

01/08/2019

Recruitment end date

31/05/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Carleton Clinic
Cumwhinton Road
Carlisle
CA1 3SX
United Kingdom

Trial participating centre

South Tyneside District Hospital
Harton Lane
South Shields
NE34 0PL
United Kingdom

Sponsor information

Organisation

Cumbria Partnership NHS Foundation Trust

Sponsor details

Carleton Clinic
Cumwhinton Road
Carlisle
CA1 3SX
United Kingdom
+441228608926
leon.jonker@cumbria.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Inotec AMD Limited

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

Internal report to the funders of the trial, Natrox wound care (part of Inotec AMD Limited) and the Academic Health Sciences Network.

A summary of the main findings will be supplied to participants who request this option on the informed consent form.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication

Intention to publish date

01/10/2021

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

29/07/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR) 11/09/2019: Uploaded protocol 17 July 2019 (not peer reviewed)