Diabetic Foot Ulcers, Diabetic Foot Wounds
Conditions
Keywords
Diabetic Foot Ulcers, Diabetic Foot Wounds
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.
Interventions
BIOLOGICALSantyl
2 mm Santyl applied once daily
PROCEDUREControl
Standard Care
Sponsors
Healthpoint
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change in Wound Area | 6 and 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Santyl Collagenase (SANTYL®) Ointment | 28 |
| Control Standard Care | 27 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Santyl | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 20 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 23 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 22 Participants | 47 Participants |
| Region of Enrollment United States | 28 participants | 27 participants | 55 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 21 Participants | 20 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 28 | 6 / 27 |
| serious Total, serious adverse events | 3 / 28 | 4 / 27 |
Outcome results
Primary
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.
Time frame: 6 and 12 weeks
Population: Primary analysis was based on the Intent-to-treat dataset which consisted of all subjects randomized to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Santyl® | Mean Percent Change in Wound Area | % change at end of 6 weeks | -68 percentage of change in wound area | Standard Error 6.3 |
| Santyl® | Mean Percent Change in Wound Area | % change at end of 12 weeks | -61 percentage of change in wound area | Standard Error 9.6 |
| Control | Mean Percent Change in Wound Area | % change at end of 6 weeks | -36 percentage of change in wound area | Standard Error 20.4 |
| Control | Mean Percent Change in Wound Area | % change at end of 12 weeks | -46 percentage of change in wound area | Standard Error 18.3 |