Safety and Efficacy Study of MedCu Wound Dressings

The Study was divided into three Phases: Screening Phase (1-2 weeks); Treatment Phase (\~ 1 month); and Follow-up Phase (two weeks). During the Screening Phase, blood samples were taken for analysis of blood count, liver and kidney functions from potential appropriate diabetic patients with chronic wounds in their foot. Stable chronic diabetic patients, whose wounds were not infected and the wound size increased or did not decreased by more than 25% per week or 35% by SOC treatment during the Screening Phase, and who will meet all other study inclusion criteria, were enrolled and start the 4 weeks Treatment Phase. The wounds were then treated by applying the Copper Oxide containing Dressings (COD) that were changed twice a week. In the two weeks post-treatment period, the patient received standard of care (SOC) dressing. In that time period, the patient were seen once after two weeks. The Primary outcome was the evaluation of the safety of the COD and the secondary outcomes were the evaluation of the wound size change of the foot wounds when using COD. Measures that were assessed included

1. Percent change in wound size during the Treatment Phase,
2. Rate of increase in extent and quality (color) of granulation tissue,
3. Infectious episodes during the Treatment Phase.

The Study was divided into three Phases: Screening Phase (1-2 weeks); Treatment Phase (\~ 1 month); and Follow-up Phase (two weeks). During the Screening Phase, blood samples were taken for analysis of blood count, liver and kidney functions from potential appropriate diabetic patients with chronic wounds in their foot. Stable chronic diabetic patients, whose wounds were not infected and the wound size increased or did not decreased by more than 25% per week or 35% by SOC treatment during the Screening Phase, and who will meet all other study inclusion criteria, were enrolled and start the 4 weeks Treatment Phase.

During the Treatment Phase, the index wounds were evaluated, undergone bed side debridement if necessary, and photographed. Tissue Analytics software was used to assess wound size and volume. The wounds were washed by normal saline or a previously used solution (but no new disinfectant or any antibacterial preparation), and then the COD was applied on the wound. The COD was applied on the wounds for the duration of the Treatment Phase and changed twice a week, once in the clinic and once at home. At every clinic visit the following assessments were performed: wound assessment, including size determination, depth, clinical impression of infection (swelling, erythema, discharge quantity and quality, granulation, fibrin and necrotic tissue, odor, pain, and tenderness); antibiotics and vital signs as necessary. After \~ 1 month of test wound dressings use, a blood sample was taken for blood count, liver and kidney functions. If needed, the patients' wounds were treated using the hospital SOC in the follow up period. The Primary outcome was the evaluation of the safety of the COD and the secondary outcomes were the evaluation of the wound size change of the foot wounds when using COD. Measures that were assessed included

1. Percent change in wound size during the Treatment Phase,
2. Rate of increase in extent and quality (color) of granulation tissue,
3. Infectious episodes during the Treatment Phase.

Eligibility Criteria:
Inclusion Criteria:

Patients must satisfy all of the following inclusion criteria to be included in the study:

1. Male or female subjects, 18 to 80 years of age at the time of enrollment.
2. Subject has Diabetes Mellitus (type 1 or type 2) by WHO criteria.
3. Wound exists for at least 4 weeks including 4 weeks from last surgical debridement in operating room (OR) or minor foot amputation.
4. The foot wound size has not decreased by more than 25% per week or 35% in two weeks by SOC during the screening period.
5. Wound size 2-30 cm2.
6. The wound does not have signs of infection as defined by Dumville et al., Topical antimicrobial agents for treating foot wounds in people with diabetes. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No.: CD011038, Table 1. For clarity, the following signs are allowed:

   1. If erythema is present at wound it should be up to 2 cm from the wound edges.
   2. If exudate is present it should be either serous or thick but not thick-purulent nor purulent
   3. Green or black necrotic tissue constitute up to 20% of the wound size.
7. The wound should not have cavities or deep sinuses. However, cover by free skin or soft tissue wall is allowed for up to 5 mm.
8. Having at least moderate blood perfusion into the affected limb as defined by palpable pulses (Dorsalis Pedis and/or Tibialis Posterior, unequivocally palpable). If no pulse is clearly present in vascular lab tests Ankle Brachial Index (ABI) should be 0.6\< or if ABI \> 1.3, then toe pressure of \> 50 mmHg.
9. Having a body mass index (BMI) \<40 Kg/m2.
10. Recent glycosylated haemoglobin (HbA1c) \<12.0%.
11. Not undergoing any systemic or topical antibiotic treatment for the wound for a week before enrollment in the study.
12. No foot deformity or bony projection that is severe enough to jeopardize wound healing as deemed to the treating physician.
13. The patient is able and eligible to sign written informed consent and participate in the study.
14. Be available for the entire study period, and ability and willingness to adhere to the requirements of the study.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following exclusion criteria:

1. General conditions:

   * A clinically significant active or unstable cardiac, gastrointestinal, endocrine, neurological, liver, or kidney disease.
   * Psychiatric condition.
   * Active participation in an investigational trial within 30 days of the screening visit.
   * History of allergic reactions attributed to copper.
   * Subjects with Active Charcot neuro-arthropathy.
   * Any chronic or acute condition susceptible of interfering with the evaluation of the wound dressing effect.
   * Individuals using and need to continue use any type of topical agents in or on the wound.
   * Any form of substance abuse (including drug or alcohol abuse, excluding cannabis), psychiatric disorder or any chronic condition susceptible, in the opinion of the investigator, of interfering with the conduct of the study.
   * Females who are pregnant, lactating, of child-bearing potential.
   * Fertile female subjects who are not willing to use an acceptable method of contraception during the treatment period and for 14 days following completion of treatment.
   * Subjects who are likely to be non-compliant or uncooperative during the study.
2. Laboratory tests:

   * Anemia (Hemoglobin \< 8.0 g/dL).
   * White Blood Cells count \> 11,000/μL.
   * Platelets count \< 100,000/μL.
   * Liver function tests \> 3 times upper normal lab values.
   * Creatinine \> 3.5 mg/dL.
   * Albumin \< 2.2g/dL.
   * Any other clinically significant blood and urinalysis tests abnormalities that can jeopardize study results as evaluated by the investigator.
3. Wound condition:

   * The wound size area has decreased by more than 25% per week or 35% in two weeks by SOC treatment during the screening phase prior to the commencement of the study.
   * Have visible bone exposed at wound site.
   * Any signs of infection in the wound (which could be linked to raised body temperature), abscess, cellulitis, necrosis, drainage or known osteomyelitis or erythema around the wound of more than 2 cm.