Diabetic Foot Ulcers, Foot Wounds
Conditions
Keywords
Diabetic Foot Ulcers, Diabetic Foot Wounds
Brief summary
This study tests two different approaches to the removal of dead tissue from the surface of a wound.
Interventions
DRUGSantyl
2 mm Santyl applied once daily.
PROCEDUREControl
Daily gauze and optional sharp debridement
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
* The informed consent document must be read, signed, and dated by the subject or the subject's legally authorized representative before conducting any study procedures or exams. In addition, the informed consent document must be signed and dated by the individual who consents the subject before conducting Visit 1. A photocopy of the signed informed consent document must be provided to the subject, and the original signed document placed in the subject's chart. * 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. * Willing 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 the Darco (orthopedic) shoe off-loading device and insole, if appropriate, starting on the day of screening and running through the follow-up phase. * A history of Type I or Type II Diabetes Mellitus requiring insulin or oral hypoglycemic medications to normalize blood glucose levels. A foot wound which is: * Superficial, involving the full skin thickness but not underlying tissues and is 0.5 cm2 to 10 cm2 in measured surface area at screening visit (not yet debrided) * Chronic, defined as open for 30 days * On a neuropathic foot, defined as inability to perceive 10 grams pressure using a Semmes-Weinstein 5.07 or equivalent monofilament in the periwound area * Adequately perfused, defined as TcPO2 \> 40 mmHg; or toe pressure \> 40 mmHg, or Doppler waveform consistent with adequate flow in the foot (biphasic or triphasic waveforms) at screening. * Acceptable state of health and nutrition with: * Serum albumin ≥ 2.0 g/dL (20g/L) * Pre-albumin levels of ≥ 15 mg/dL (0.15g/L). * Per Screening lab chemistry† report: * 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 blood urea nitrogen (BUN) \< 75 mg/dL * Serum creatinine 4.5 mg/dL * HbA1c 12% * Per Screening lab hematology† report: * Hemoglobin (Hgb) \> 8.0 g/dL * White blood cells (WBC) \> 2.0 109/L * Absolute neutrophil count \> 1.0 109/L * Platelet count \> 50 109/L. * Local laboratories will be used, but the ranges for inclusion are set based on Healthpoint Data Management ranges. Refer to Appendix 18.1.2.
Exclusion criteria
* Contraindications or hypersensitivity to the use of the study medications or their components (refer to product labels). * Target wound does not require debridement, or is covered with dry eschar. * Uncontrolled bleeding disorder. * Untreated cellulitis extending \>2 cm around the target wound, untreated lymphangitic streaking, spread beneath the superficial fascia, deep-tissue abscess, gangrene, or infection of muscle, tendon, joint or bone. * Infection in a patient with systemic toxicity or metabolic instability (e.g., fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe hyperglycemia, or azotemia). * Any of the following: * Target wound tunneling per probing and visual assessment * Osteomyelitis of the target foot or wound probes to bone * Target wound is on the heel * Target wound is over a Charcot deformity which cannot be offloaded. * Diagnosis of chronic granulomatous disease, leukocyte adhesion defects or severe neutropenia * Treatment with any of the following: * Systemic corticosteroids * Immunosuppressive agent(s) * Chemotherapeutic agent(s) * Antiviral agent(s) * Platelet-derived growth factor * Living skin equivalent * Dermal substitute * Radiation therapy to the target lower extremity within 30 days prior to signing the informed consent document. * Currently on systemic antibiotic therapy * Any medical condition judged by the Medical Monitor and/or Investigator to cause the study to be detrimental to the subject (specify on the reason for screen failure if this applies).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bates-Jensen Wound Assessment Score - Modified (BWAT-m) | baseline and 28 days | The Bates-Jensen Wound Assessment Score was used to collect information about the wound bed appearance in each of 8 categories (sub-scales) each with a possible score of 1 to 5. For each sub-scale intact skin was scored a one (1) while a five (5) would indicate the worst possible rating. All scores were combined to compute a total score for each arm/group, with a score of 8 indicating intact skin (minimum summed score), and a score of 40 indicating the worst possible rating (maximum summed score). |
Secondary
| Measure | Time frame |
|---|---|
| Percent of Wound Area Change From Baseline at End of Treatment | baseline and 28 days |
| Percent of Wound Area Change From Baseline at the End of 12 Week Follow-up | baseline and 84 days |
Countries
United States
Participant flow
Recruitment details
4/1/2010 to 8/2/2011 at 7 clinics in the U.S.
Participants by arm
| Arm | Count |
|---|---|
| Santyl 2 mm Santyl once daily (QD) | 24 |
| Control Daily gauze and optional sharp debridement | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | Control | Santyl | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 9 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 15 Participants | 28 Participants |
| Age Continuous | 63.5 years STANDARD_DEVIATION 9.8 | 58.5 years STANDARD_DEVIATION 13.3 | 61.0 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment United States | 24 participants | 24 participants | 48 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 9 / 24 |
| serious Total, serious adverse events | 2 / 24 | 4 / 24 |
Outcome results
Primary
Bates-Jensen Wound Assessment Score - Modified (BWAT-m)
The Bates-Jensen Wound Assessment Score was used to collect information about the wound bed appearance in each of 8 categories (sub-scales) each with a possible score of 1 to 5. For each sub-scale intact skin was scored a one (1) while a five (5) would indicate the worst possible rating. All scores were combined to compute a total score for each arm/group, with a score of 8 indicating intact skin (minimum summed score), and a score of 40 indicating the worst possible rating (maximum summed score).
Time frame: baseline and 28 days
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Santyl | Bates-Jensen Wound Assessment Score - Modified (BWAT-m) | 15.8 units on a scale | Standard Deviation 4.5 |
| Control | Bates-Jensen Wound Assessment Score - Modified (BWAT-m) | 13.8 units on a scale | Standard Deviation 4.8 |
Comparison: The BWAT-m scores were compared at each of the 4 treatment weeks and at the end of the follow-up using a mixed-effects ANCOVA for the intent-to-treat population. Treatment and treatment week, as well as their interaction, were defined as fixed effects with subject as a random effect. The BWAT-m score at baseline was used as a covariate.p-value: =0.208ANCOVA
Secondary
Percent of Wound Area Change From Baseline at End of Treatment
Time frame: baseline and 28 days
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Santyl | Percent of Wound Area Change From Baseline at End of Treatment | -44.9 percentage of baseline wound area | Standard Error 17 |
| Control | Percent of Wound Area Change From Baseline at End of Treatment | 0.8 percentage of baseline wound area | Standard Error 57.2 |
Comparison: Null hypothesis: no differences between the 2 treatments with the alternative of non-zero differences. 48 evaluable subjects is sufficient to detect an effect size of 0.80.p-value: =0.2737ANCOVA
Secondary
Percent of Wound Area Change From Baseline at the End of 12 Week Follow-up
Time frame: baseline and 84 days
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Santyl | Percent of Wound Area Change From Baseline at the End of 12 Week Follow-up | -53.8 percentage of baseline wound area | Standard Error 17.7 |
| Control | Percent of Wound Area Change From Baseline at the End of 12 Week Follow-up | 8.1 percentage of baseline wound area | Standard Error 54.2 |
Comparison: Null hypothesis: no differences between the 2 treatments with the alternative of non-zero differences. 48 evaluable subjects is sufficient to detect an effect size of 0.80.p-value: =0.2741ANCOVA
Post Hoc
Change From Baseline in Wound Area - Control Group
Wound area at the end of treatment visit compared to the wound area at baseline for each subject
Time frame: baseline and 28 days
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Santyl | Change From Baseline in Wound Area - Control Group | Baseline wound area | 2.4 square centimeters | Standard Deviation 2.1 |
| Santyl | Change From Baseline in Wound Area - Control Group | Wound area at 28 days | 2.3 square centimeters | Standard Deviation 4.9 |
Comparison: Paired t-test, 2-sided, alpha = 0.05p-value: =0.9392t-test, 2 sided
Post Hoc
Change From Baseline in Wound Area - Santyl Treatment Group
Wound area at the end of treatment visit compared to the wound area at baseline for each subject
Time frame: baseline and 28 days
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Santyl | Change From Baseline in Wound Area - Santyl Treatment Group | Baseline wound area | 3.0 square centimeters | Standard Deviation 2.1 |
| Santyl | Change From Baseline in Wound Area - Santyl Treatment Group | Wound area at 28 days | 1.8 square centimeters | Standard Deviation 2.5 |
Comparison: Paired t-test, 2-sided, alpha = 0.05p-value: =0.0164t-test, 2 sided