Using Santyl on Diabetic Foot Ulcers

Study Overview
=================
Brief Summary
-----------------
Subjects enrolled in this study will either use Santyl daily or follow standard care procedures for up to 6 weeks for their diabetic foot wound. After 6 weeks of treatment, the subjects will continue into the follow-up phase for an additional 6 weeks. Study doctors will look at the wound in the office each week (up to 12 weeks) to see if the wound is healing. Depending on a number of factors at each office visit, the study doctors may also use a procedure called sharp debridement to remove dead skin from the wound. This study will test the hypothesis that daily treatment of diabetic foot wounds with Santyl will result in more rapid healing, healthier wounds, and fewer required sharp debridements over the study period than for diabetic foot wounds treated in other ways.

Official Title
-----------------
A Comparison of Collagenase Santyl® Ointment Used Adjunctively to Sharp Surgical Debridement and Sharp Surgical Debridement in the Care of Diabetic Foot Wounds

Conditions
-----------------
Diabetic Foot Ulcers, Diabetic Foot Wounds

Intervention / Treatment
-----------------
* Biological: Santyl
* Procedure: Control


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Subjects 18 years of age or older. Subjects may be of either sex and of any race or skin type provided that their skin color, in the opinion of the Investigator, will not interfere with the study assessments. A target ulcer which is 0.5 cm2 - 10 cm2 inclusive (as measured at the Screening Visit) with a duration ≥ 30 days (documented in the patient's history or by patient report of onset) which requires sharp surgical debridement. Adequate arterial blood flow as evidenced by an ankle brachial index (ABI) of > 0.7 and ≤ 1.1. If the ABI is greater than 1.1, then a toe pressure of > 40 mmHg OR a TcPO2 ≥ 40 mmHg must be present. Either toe pressure or TcPO2 is also acceptable as a stand-alone measurement, but if both are obtained, each must meet its respective cutoff. Alternatively, a Doppler waveform consistent with adequate flow to the region of the foot with the target ulcer (biphasic or triphasic waveforms) is acceptable. A target ulcer that is not infected based on clinical assessment. 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 whenever necessary to keep weight off of any foot ulcers. History of diabetes mellitus (Type 1 or 2) requiring insulin or oral hypoglycemic medications to control blood glucose levels. CBC and blood chemistry values as follows: Serum albumin ≥ 2.0 g/dL Pre-albumin levels of ≥ 15 mg/dL Alkaline phosphatase ≤ 500 U/L Alanine aminotransferase (ALT) ≤ 200 U/L Aspartate aminotransferase (AST) ≤ 175 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 EXCLUSION CRITERIA Contraindications or hypersensitivity to the use of the study medications or their components. Target ulcer does not require debridement. Uncontrolled bleeding disorder. Cellulitis of the target wound, 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). Any of the following: Target ulcer tunneling Target ulcer requires hyperbaric or negative pressure therapy per the investigator's medical judgment Target ulcer is on the heel and cannot be offloaded Target ulcer is over a Charcot deformity which cannot be offloaded NOTE: A heel ulcer or an ulcer over a Charcot is not excluded unless effective offloading is not possible. Current, ongoing osteomyelitis of the target foot as determined by medical history. Participation in another investigational clinical study within thirty (30) days of the Screening Visit. A target ulcer which involves underlying tissues (i.e., fat, fascia, tendon, muscle, bone). A target ulcer on a non-neuropathic foot (neuropathic defined as inability to perceive 10 grams pressure using a Semmes-Weinstein 5.07 or equivalent monofilament in the periwound area). NOTE: Monofilament test result must be documented. 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 Immunosuppressive agents Chemotherapeutic agents Antiviral agents Platelet-derived growth factor (e.g., Regranex) Living skin equivalent (e.g., Apligraf) Dermal substitute (e.g., Dermagraft, Integra, etc.) Systemic antibiotic therapy or topical antibiotic treatment of the target ulcer Radiation therapy to the target lower extremity within 30 days prior to screening The Medical Monitor and/or Investigator may declare any subject ineligible for a valid medical reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Santyl<br>2mm Santyl applied once daily. | Biological: Santyl<br>* 2 mm Santyl applied once daily<br>|
| Active Comparator: Control<br>Standard Care | Procedure: Control<br>* Standard Care<br>* Other names: Standard Care;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in Wound Area | Wound area was measured using the ARANZ Silhouette digital wound imaging and measurement device. The average percent (%) of change from baseline of the target wound area at the end of the 6-week treatment period and the end of the entire 12-week study period respectively, was calculated using a two-way ANCOVA model. | 6 and 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetic Foot Ulcers, Diabetic Foot Wounds