Use of Santyl in Diabetic Foot Ulcers
Condition: Diabetic Foot; Foot Ulcer, Diabetic
MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer
Intervention: Santyl; Product containing silver
Intervention description: Silver product not specified by the protocol; Investigators choose the appropriate silver containing product for each diabetic foot ulcer
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Diabetes; diabetic foot ulcer; foot sore; type 2 diabetes; type 1 diabetes; neuropathy; DFU

Summary:

      This study is designed to test the hypothesis that daily treatment of diabetic foot ulcers
      with an enzymatic debriding agent, SANTYL, for up to 6 weeks will result in more rapid
      decrease in ulcer area than diabetic foot ulcers treated with a topical treatment containing
      silver. After meeting study criteria, participants will be randomly assigned to apply SANTYL
      or a topical treatment containing silver to their to foot ulcer for up to 6 weeks. At the end
      of 6 weeks, participants will be followed for an additional 4 weeks to examine the outcome of
      the study treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent, which will consist of reading, signing, and dating
             the informed consent document after the Investigator, sub-Investigator or other
             designated study staff member has explained the study procedures, risks, and contact
             information.

          2. Eighteen (18) years of age or older, of either sex, and of any race or skin type.

          3. Willing and able to make all required study visits.

          4. Able to follow instructions and perform the dressing changes at home or have a
             caregiver who can perform the dressing changes according to the protocol.

          5. Willing to use an appropriate off-loading device to keep weight off of foot ulcers.

          6. An ulcer present on any part of the plantar surface of the neuropathic foot or hallux
             which is 0.5 cm2 - 10 cm2 inclusive (as measured at the Screening Visit using the
             ARANZ Silhouette imaging device). The target ulcer duration must be ≥ 6 weeks but not
             more than 52 weeks (12 months) as documented in the subject's history or by subject
             report of onset, and which requires debridement.

          7. Adequate arterial blood flow as evidenced by an ankle brachial index (ABI) of > 0.70
             and ≤ 1.20. If ABI > 1.2, perfusion at or near the site of the ulcer should be
             confirmed; the foot is warm to the touch and has palpable pulses.

          8. Separation of at least 5 cm (closest ulcer edge to other closest ulcer edge) if ≥ 2
             ulcers are present as measured using the ARANZ Silhouette imaging device.

          9. Diabetes mellitus (Type 1 or 2) requiring insulin or oral/injectable medications to
             control blood glucose levels.

         10. Target ulcer is not infected based on clinical assessment.

        Exclusion Criteria:

          1. Contraindications or hypersensitivity to the use of clostridial collagenase or
             products containing silver.

          2. Participation in another clinical trial within thirty (30) days of Visit 1, or planned
             participation overlapping with this study.

          3. Bleeding disorder that would preclude sharp debridement during the study.

          4. Active cellulitis of the target ulcer, lymphangitic streaking, deep tissue abscess,
             gangrene, or infection of muscle, tendon, joint or bone.

          5. Infection with systemic toxicity or metabolic instability (e.g., fever, chills,
             tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe
             hyperglycemia, azotemia).

          6. A target ulcer which involves the underlying tissues of tendon, muscle, or bone.

          7. Diagnosis of chronic granulomatous disease, leukocyte adhesion defects, or severe
             neutropenia.

          8. Current treatment (at the time of the Screening Visit) with any of the following:

               -  Systemic corticosteroids. If corticosteroid treatment was for ≥ 10 days, there
                  must be a 1 week interval between discontinuation and screening.

               -  Immunosuppressive agents

               -  Chemotherapeutic agents

               -  Antiviral agents

               -  Systemic antibiotic therapy (for any reason) or topical antibiotic treatment of
                  the target ulcer

          9. Treatment of target ulcer with bioactive therapies within 1 month of screening:

               -  Platelet-derived growth factor (e.g., Regranex®)

               -  Living skin equivalent (e.g., Apligraf®)

               -  Dermal substitute (e.g., Dermagraft®, Integra®, Oasis®, etc.)

               -  Amniotic membrane products (e.g., EpiFix®, Grafix®, etc.)

         10. Prior treatment of target ulcer for any length of time with clostridial collagenase
             ointment (SANTYL®).

         11. Radiation therapy to the target lower extremity within 30 days prior to screening.

         12. Medical or physical condition that, in the opinion of the Investigator, would preclude
             safe subject participation in the study.

         13. Blood counts and blood chemistry values as follows:

               -  Alanine aminotransferase (ALT) > 3x upper limit of normal

               -  Aspartate aminotransferase (AST) > 3x upper limit of normal

               -  Gamma Glutamyl Transferase (GGT) > 2.5x upper limit of normal

               -  Serum albumin < 2.0 g/dL • Pre-albumin levels of < 10 mg/dL

               -  Alkaline phosphatase > 500 U/L • Serum total bilirubin > 3.0 mg/dL

               -  Serum BUN > 75 mg/dL • Serum creatinine > 4.5 mg/dL

               -  HbA1c > 12% • Hemoglobin (Hgb) < 8.0 g/dL

               -  WBC < 2.0 x 109/L • Absolute neutrophil count < 1.0 x 109/L

               -  Platelet count < 50 x 109/L