A Single Center Pilot Study to Examine the Effect of NATROX Oxygen Wound Therapy on Non-healing Wounds and the Practical Implication of Introducing a Remote Monitoring and Telehealth Solution to Manage These Complex Patients in the Home Setting.
Conditions: Non-healing Wounds
Sponsor: Inotec AMD Limited

 
 pg. 1  
                                                                                                                                                                                                                                                 March 29, 2021 
 
STUDY PROTOCOL 
Title of Study: A single center pilot study to examine the effect of NATROX® Oxygen Wound Therapy on non-healing wounds and the practical implication of introducing 
a remote monitoring and telehealth solution to manage these complex patients in the home care setting. 
 
 
Study Title: 
 
A single center pilot study to examine the effect of NATROX® Oxygen Wound Therapy on non-healing wounds and 
the practical implication of introducing a remote monitoring and telehealth solution to manage these complex 
patients in the home care setting. 
Rationale: 
There is a wealth of evidence to support the benefits of oxygen therapy on wound healing1-7. Oxygen is required for 
all major processes of wound healing and wound hypoxia is common. Skin wounds can receive oxygen from the 
blood stream via perfusion and from oxygen uptake through the skin. Yet, both wound perfusion and blood oxygen 
levels are frequently insufficient in patients with chronic wounds due to poor circulation, vascular disruption, and 
vasoconstriction, thereby reducing the wound’s capacity to heal. 
Diabetic ulcers, vascular ulcers (venous or arterial), and pressure injuries are all chronic wounds. The pathologies 
underlying chronic wounds can differ widely. However, common shared features include prolonged or excessive 
inflammation, persistent infections, and the inability to respond to reparative stimuli8,9. Adults with vascular disease 
and/or diabetes are at highest risk for chronic leg and foot wounds. The ischemic (reduced tissue perfusion) and/ or 
hypoxic lower limb conditions which result from these conditions reduces availability of both oxygen and nutrients, 
making these wounds especially hard to heal. These wounds last on average 12 to 13 months, but this varies widely; 
many will remain open for years or never heal8,9, and up to 30% of DFUs go onto amputation10. Even when they do 
heal, wounds recur in 60-70% of patients, decrease quality of life, and are a significant cause of morbidity8,9. 
 
The need for telehealth and remote patient monitoring in the current climate is critical and reinforces the VA’s 
strategy to protect and care for Veterans, their families, heath care providers and staff in the face of this pandemic.  
The VA’s tactic to shift outpatient care to a “telehealth” mode, with phone, video and/or electronic communication 
to meet the needs of the ambulatory patient is difficult to achieve in wound care as clinicians relies heavily on the 
visual appearance of the wound to direct their therapy decisions. Thus, it is imperative to validate a remote 
monitoring tool that offers standard telehealth care as well as accurate, consistent, and simple wound 
measurement and imagery. Having the ability to manage complex wounds accurately should enable quick 
identification of early warning signs that the wound is deteriorating thus facilitating appropriate triaging of patients 
that need urgent face to face medical review. 
Study Design: 
Consecutive case series 

 
 pg. 2  
                                                                                                                                                                                                                                                 March 29, 2021 
 
Patient population 
6 - 12 patients meeting eligibility criteria 
Number of Sites: 
Single Site 
Inclusion criteria: 
Patients must fulfil all 
the following criteria to 
be eligible for inclusion 
into the study: 
 
1. Male or female 18 years of age and older 
2. Subjects having a non-healing wound of any etiology, except 3rd degree burns 
3. No visible signs of healing objectively, less than 30% reduction in wound size in the last 4 weeks 
4. Wound present for at least 4 weeks but less than 12 months 
5. Subjects’ wound size is minimum of 1 cm2 and maximum of 25cm2  
6. Subject is able and willing to participate in self care 
7. Subject is able and willing to follow the protocol requirements 
8. Subject has signed informed consent 
Exclusion criteria 
Patients who met any 
one of the following 
criteria during screening 
visit are not eligible to 
participate into the 
study: 
 
 
1. Subject has a life expectancy < 1 year 
2. Subject is unable to manage the NATROX® device (charge and change the batteries daily) 
3. Subject unable or reluctant to use iPhone and imaging technology  
4. Subject has ulcers that are completely necrotic or if the clinician felt it was clinically necessary to cover the wound 
surface in gel or creams that would prevent the transmission of oxygen to the wounds surface 
5. Subject has major uncontrolled medical disorder(s) such as serious cardiovascular, renal, liver or pulmonary disease, 
lupus, palliative care or sickle cell anemia;  
6. Subject currently being treated for an active malignant disease or patients with history of malignancy within the 
wound 
7. The subject has other concurrent conditions that in the opinion of the investigator may compromise subject safety  
8. Known contraindications to the NATROX® 
9. Known allergies to any of the NATROX® components 
10. Know allergies to adhesives 
Discontinuation criteria 
1. Signs of allergic or hypersensitivity to any components of NATROX®   
2. Onset of any condition that could severely interfere with investigational treatment evaluation 
3. Investigator’s decision to withdraw the patient  
4. Patient’s decision to withdraw consent 
5. Need to use a prohibited medication/therapy 
Endpoints 
Primary endpoint: 
- 
Number of participate that achieve complete wound closure during the 12-week study 

 
 pg. 3  
                                                                                                                                                                                                                                                 March 29, 2021 
 
- 
The percentage change in ulcer size at 12 weeks relative to baseline measurement – this parameter will be 
performed using the eKare platform. 
Secondary endpoint: 
The effectiveness of the remote management tool for:  
- 
Reducing number of face to face clinic visits necessary 
- 
Improved communication between hospital and home around wound progression 
- 
Ease of implementation and acceptance by the patient 
- 
Early warning and triaging wound issues 
- 
Increase confidence in proactively managing patient remotely 
Method: 
 
 
 
 
 
 
 
Prior to recruitment participants should have clinical documentation of wound progression for a minimum of 2 
weeks, including wound measurements, if accurate data unavailable, participants wound progression will be 
monitored for 2 weeks prior to therapy intervention. Wound debridement and the use of off-loading, where 
appropriate will be at the discretion of the wound specialist throughout the study. On recruitment a full wound 
assessment will be completed in the eKare platform, this will act as the point of reference. Participants will be 
commenced on NATROX® Oxygen Wound Therapy with an adhesive foam dressing as a secondary dressing, 
frequency of dressing changes will be dictated by exudate levels and clinical judgement. The participant will be given 
a specially configured iphone (eKare patient App and NATROX® Patient library) along with any relevant personalised 
instructions, this could include a video of their dressing regime to support self application. 
For the first 4 weeks following recruitment, wounds will be monitored remotely by the wound specialist with a face 
to face clinical reviews every 2 weeks. Patients will be instructed to photograph the wound via the eKare app at 
each dressing change (minimum of once weekly) which will be transmitted to the wound specialist. Following the 
initial 4 weeks of therapy, face to face clinical reviews can be extended to every 4 weeks, based on clinical 
judgement.  
Participant will have a weekly clinical review performed via the eKare app for the duration of the study or till the 
wound heals, whatever comes first. Prior to the weekly review, patient will be asked 5 questions (with yes or no 
answers only) to help identify early warning signs of wound problems along with any compliance issues with the 
chosen therapy. During the study if self application, compliance, or wound issues are identified by either the 
participant or highlighted through the eKare monitoring tools, participants can be triaged for additional clinical 
intervention or support as deemed appropriate.  
 
 
References 

 
 pg. 4  
                                                                                                                                                                                                                                                 March 29, 2021 
 
1. Asmis, R., Qiao, M. & Zhao, Q. (2010) Low flow oxygenation of full-excisional skin wounds on diabetic mice improves wound healing by accelerating wound closure and 
reepithelialization. International Wound Journal 7, 349-357. 
2. Babior, B.M. (1978) Oxygen-dependent microbial killing by phagocytes (first of two parts). New England Journal of Medicine. 298, 659-668. 
3. Knighton, D.R., Silver, I.A. & Hunt, T.K. (1981) Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery 90, 262-
270. 
4. Lordish, H. (2000) Molecular cell biology, Freeman, New York. 
5. Sen, CK (2003) The general case for redox control of wound repair. Wound Repair and Regeneration 11, 431-438. 
6. Stephens, FO and Hunt, TK (1971) Effect of changes in inspired oxygen and carbon dioxide tensions on wound tensile strength: an experimental study. Annal of Surgery 
173, 515-519. 
7. Sundaresan, M et al. (1996) Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. Biochemisty Jounal 318 ( Pt 2), 379-382. 
8. Frykberg, R.G. & Banks, J. Challenges in the Treatment of Chronic  Wounds. Advances in wound care 4, 560-582 (2015). 
9. Richmond, N.A., Maderal, A.D. & Vivas, A.C. Evidence-based  management of common chronic lower extremity ulcers.  Dermatologic therapy 26, 187-196 (2013). 
10. Stockl, K., Vanderplas, A., Tafesse, E. & Chang, E. Costs of lower-  extremity ulcers among patients with diabetes. Diabetes Care 27,  2129-2134 (2004) 
 
 
Attachments: 
Health Questionnaire prior to NATROX® Oxygen Wound Therapy + Visual Analogue Score 
NATROX Schedule of Events