The Effect of Natrox® Oxygen Wound Therapy on the Healing Rate of Chronic Diabetic Foot Ulcers

A Multicentre Randomized Controlled Trial to Investigate the Effect of Natrox Topical Oxygen Wound Therapy on the Healing rates of Diabetic Foot Ulcers.

Patients with diabetic foot ulcers will be enrolled into the trial at multiple wound care centers and hospital research centers across the United States of America. After qualifying per protocol, patients will be randomized to receive standard wound care or standard wound care plus Topical Oxygen Wound Therapy for their wounds. Patients will be monitored for 12 weeks. The primary comparator between the groups will be complete wound healing at 12 weeks, but other parameters will be assessed, such as pain, wound size reduction and infection status.

Eligibility Criteria:
Inclusion Criteria

1. Subjects are male or female, 18 years of age or older. At least 50% of the enrolled population must be ≥ 65 years of age.
2. Subjects with one of the following wounds:

   A. Diabetic foot ulcer present for greater than 4 weeks (documented in the medical record) but less than 12 months duration if being treated with active SOC.

   B. Minor amputation wound sites
3. Subject has clinical documentation of no visible wound improvement in the after 4 weeks of standard of care. Objectively, less than 40% healing in the past four weeks from the first treatment visit.
4. Study ulcer is a minimum of 0.5 cm2 and a maximum of 25 cm2 at first treatment visit
5. Subjects' wound score on ISDA tool is Grade 1 or 2.
6. The subject is able and willing to follow the protocol requirements
7. Subject has signed informed consent
8. Adequate circulation to the affected foot as demonstrated by a dorsum transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg; an ABI between 0.7 and ≤ 1.3, or TBI of \>6 within 3 months of the first Screening Visit.
9. Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence).
10. The target ulcer has been offloaded for at least 14 days prior to randomization.

Exclusion Criteria

1. Subject has a known life expectancy of \< 1 year
2. Subject or caregiver is unable to manage the Natrox® device (charge and change batteries daily)
3. Subject has ulcers that are completely necrotic or if the clinician feels it is clinically necessary to cover the wound surface in gel or creams that would prevent the transmission of oxygen to the wound surface.
4. Subject has major uncontrolled medical disorders such as serious cardiovascular, renal, liver or pulmonary disease, lupus, palliative care or sickle cell anemia.
5. Subject currently being treated for an active malignant disease or subjects with history of malignancy within the wound.
6. The Subject has other concurrent conditions that in the opinion of the Investigator may compromise subject safety
7. Known contraindications for the Natrox system
8. Known allergies to any of the Natrox system components
9. Concurrent participation in another clinical trial that involves an investigational drug or device that would interfere with this study.
10. Index ulcer has reduced in area by 20% or more after 2 weeks of standard of care from the first screening visit (S1) to the TV1/randomization visit.
11. Subject is pregnant or breast feeding.
12. Subjects with a history of more than two weeks treatment with immunosuppressants (including systemic corticosteroids \>10mg daily dose), cytotoxic chemotherapy, or application of topical steroids to the ulcer surface within one month prior to first Screening Visit, or who receive such medications during the screening period, or who are anticipated to require such medications during the course of the study.
13. Index ulcer has been previously treated with tissue engineered materials (e.g. Apligraf® or Dermagraft®) or other scaffold materials (e.g. Oasis, Matristem) within the last 30 days preceding the first treatment visit.
14. Affected extremity requiring hyperbaric oxygen during the trial or within 2 weeks of treatment visit 1.
15. Known HbA1C \>12%
16. An ulcer that has visible signs of improvement in the four weeks prior to randomization defined objectively as a 40% reduction in surface area in the four weeks prior to enrollment.
17. An ulcer that has healed by more than 20% in the 2 weeks prior to screening: "historical" run-in period.