IDEAL: Efficacy of Porcine Placental Extracellular Matrix Augmented Plus Standard of Care (SOC) Versus SOC Alone for the Management of Diabetic Foot Ulcers

Evaluating the Efficacy of Porcine Placental Extracellular Matrix Augmented Wound Care Against Standard Wound Care for the Management of Diabetic Foot Ulcers: A Multi-center, Prospective, Observer-blinded, Randomized Controlled Clinical Trial.

A multi-center, prospective, observer-blinded, randomized controlled clinical trial to evaluate the efficacy of PPECM augmented standard of care versus standard of care alone in the management of hard-to-heal diabetic foot ulcers.

Inclusion:

1. Subjects at least 21 years old. At least 50% of the enrolled population must be > 65 years of age.

2. Known history of type 1 or type 2 diabetes.

3. The patient must have a target ulcer meeting the following characteristics:

   i. A diabetic ulcer that is either Wagner Grade 1 or Wagner Grade 2 . ii. Located on the anatomical foot; defined as a minimum of 50% of ulcer area extending distal to the medial malleolus.

   iii. The target ulcer must have been present for a minimum of 4 weeks and no longer than 52 weeks.

   iv. The target ulcer must display evidence of delayed wound healing, defined as less than 50% wound area reduction over the four weeks preceding randomization.

   v. At randomization subjects must have a target ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 25.0 cm2 measured post-debridement.

4. If two or more diabetic foot ulcers with the same Wagner Grade are present, the Index ulcer must additionally be:

   i. the ulcer with the largest wound area; ii. ≥ 2cm distant from any other ulcer on the affected limb, post-debridement; iii. the only ulcer to be evaluated by the study (one patient, one wound).

5. Subject has adequate circulation to the affected extremity, as demonstrated by at least one of the following within the past 30 days i. ABI ≥ 0.7 and ≤ 1.3; ii. TBI ≥ 0.6; iii. TCOM ≥ 40 mmHg; iv. PVR: biphasic.

6. BMI ≤45

7. Subject is willing to participate in all procedures and follow-up evaluations necessary to complete the study.

8. Subject has signed informed consent.

Exclusion:

1. The potential subject is known to have a life expectancy of <6 months.

2. Index Ulcers will be excluded if they meet any of the following criteria upon assessment:

   i. Index ulcer determined to be due to a condition other than diabetes ii. Active Charcot deformity OR major structural abnormalities of the foot iii. Known or suspected local skin malignancy to the index diabetic ulcer iv. Wound duration >12 months without intermittent closure

3. The target ulcer exhibits 2 or more of the following signs or symptoms consistent with clinical infection:

   i. erythema that extends ≥ 0.5cm from wound edge ii. local increased warmth iii. purulent exudate iv. local swelling or induration v. local tenderness or pain

4. Presence of osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence.

5. The potential subject is receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent), radiation therapy, cytotoxic chemotherapy, or is taking medications that the Principal Investigator believes will interfere with wound healing (e.g., biologics).

6. The potential subject has applied topical steroids to the ulcer surface within one month of initial screening.

7. The potential subject has glycated hemoglobin (HbA1c) greater than or equal to 12% within 3 months of the initial screening visit.

8. The surface area of the target ulcer, as measured by digital planimetry or manual linear measurements (e.g. with a ruler), decreases by more than 25% in the 2 weeks prior to the initial screening visit ("historical" run-in period).

9. The surface area of the target ulcer, as measured by digital planimetry, decreases by more than 25% or more during the active 2-week screening phase: the 2 weeks from the initial screening visit (SV-1) to the TV-1 visit during which time the potential subject received SOC.

10. The potential subject is unable to adhere to therapeutic offloading, if required by anatomical location of target ulce.

11. Women who are pregnant or considering becoming pregnant within the next 6 months.

12. The potential subject has end stage renal disease requiring dialysis.

13. Participation in another clinical trial involving treatment with an investigational product within the previous 30 days.

14. A potential subject who, in the opinion of the Investigator, has a medical or psychological condition that may interfere with study assessments.

15. The potential subject was treated with hyperbaric oxygen therapy (HBOT) or a Cellular, Acellular, Matrix-like Product (CAMP) in the 30 days prior to the initial screening visit.

16. The potential subject has a malnutrition indicator score <17 as measured on the Mini Nutritional Assessment.

17. Potential subjects with a sensitivity or allergy to porcine materials or collagen will be excluded.

18. Potential subjects with religious or personal objection to use of porcine- or animal-derived materials will be excluded.

19. A subject with a disorder that would create unacceptable risk of treatment complications is excluded.

20. Subjects will be considered ineligible for enrolment if any of the following criteria are met:

    i. Immune system disorders including Systemic Lupus Erythematosus (SLE), Acquired Immunodeficiency Syndrome (AIDS) or HIV.

    ii. In the past 6 months, having undergone a revascularization procedure aimed at increasing blood flow in the target limb OR any amputation affecting the target limb