Use of Santyl in Diabetic Foot Ulcers

The objectives of this study were to compare outcomes of diabetic foot ulcers (DFUs) treated with SANTYL or silver-containing products, both in combination with sharp debridement as needed. One hundred two subjects with qualifying DFUs were randomized to daily treatment with either SANTYL or a silver-containing product for 6 weeks followed by a 4 -week follow-up period. The primary outcome was the mean percent reduction in DFU area. A secondary outcome was the incidence of ulcer infections between groups.

Inclusion criteria

• 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.
• Eighteen (18) years of age or older, of either sex, and of any race or skin type.
• Willing and able to make all required study visits.
• 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.
• Willing to use an appropriate off-loading device to keep weight off of foot ulcers.
• 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.
• 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.
• 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.
• Diabetes mellitus (Type 1 or 2) requiring insulin or oral/injectable medications to control blood glucose levels.
• Target ulcer is not infected based on clinical assessment.

Exclusion criteria

• Contraindications or hypersensitivity to the use of clostridial collagenase or products containing silver.
• Participation in another clinical trial within thirty (30) days of Visit 1, or planned participation overlapping with this study.
• Bleeding disorder that would preclude sharp debridement during the study.
• Active cellulitis of the target ulcer, lymphangitic streaking, deep tissue abscess, gangrene, or infection of muscle, tendon, joint or bone.
• Infection with systemic toxicity or metabolic instability (e.g., fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe hyperglycemia, azotemia).
• A target ulcer which involves the underlying tissues of tendon, muscle, or bone.
• Diagnosis of chronic granulomatous disease, leukocyte adhesion defects, or severe neutropenia.
• 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
• 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.)
• Prior treatment of target ulcer for any length of time with clostridial collagenase ointment (SANTYL®).
• Radiation therapy to the target lower extremity within 30 days prior to screening.
• Medical or physical condition that, in the opinion of the Investigator, would preclude safe subject participation in the study.
• 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