Diabetic Foot Ulcers
Conditions
Brief summary
The purpose of this study is to assess the effect of four weeks of treatment with Santyl Ointment, compared to White Petrolatum, on the change from baseline in wound area of diabetic foot ulcers over four weeks, and on the proportion of subjects achieving complete wound closure within 12 weeks from initiation of treatment.
Interventions
DRUGSantyl
Apply an amount sufficient (thickness of a nickel) to cover the wound area. It will be applied once daily during the treatment phase, up to four weeks.
OTHERWhite Petrolatum
Apply an amount sufficient (thickness of a nickel) to cover the wound area. It will be applied once daily during the treatment phase, up to four weeks.
Sponsors
Healthpoint
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The informed consent document Photography Release 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 the screening visit. 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. * Age 18 years and older. Subjects may be of either sex and of any race or skin type. * Women of child-bearing potential (those who are not premenarchal, not surgically sterilized \[hysterectomy or bilateral oophorectomy\], or not post-menopausal) may participate in the study if they meet all of the following conditions: * they are not breast feeding * undertake an HCG serum pregnancy test, which must be negative * they do not intend to become pregnant during the study * they are using adequate birth control methods and they agree to continue using those methods for the duration of the study * Post-menopausal is defined as no period in the previous 12 months Adequate birth control methods are defined as: hormonal-topical, oral, implantable or injectable contraceptives; mechanical-spermicide in conjunction with a barrier such as a condom or diaphragm; IUD; or, surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, she must agree to use an adequate birth control method as described above for the remainder of the study. NOTE: Women who have had a bilateral tubal ligation are not considered to have been surgically sterilized and must agree to the conditions as specified above. * Willing to make all required study visits and to use the Darco shoe off-loading device and insole. * Able to follow instructions, particularly regarding the application of test articles and dressings at home. Able to apply the test article, or has a caregiver available to apply the test article according to the protocol. * Have a diabetic foot ulcer, Wagner Grades† 1 or 2, on the plantar surface of the foot. * Target ulcer present for at least 28 days, but no longer than 18 months, and has failed to close by ≥ 40% during the first 4 weeks of therapy administered during the past 4 to 8 weeks. * Target ulcer area between 2 and 15 cm², post debridement, if required. 9- 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 \> 30 mmHg OR a TcPO2 ≥ 40 mmHg; either secondary measure is acceptable, but if both are obtained, each must meet its respective cutoff. * 10\. Reasonable control of blood glucose, as evidenced by a serum HbA1C ≤ 12% at screening. * 11.Acceptable state of health and nutrition as evidenced by a serum pre-albumin level ≥ 15 mg/dL (0.15 g/L) and serum albumin ≥ 2.0 g/dL (20 g/L) at screening. * 12\. Hematology values in the following ranges: WBC ≥ 3.0x109/L Hgb ≥ 10.0 g/dL Neutrophils ≥ 1.5x109/L Platelets ≥ 75 x109/L Normal blood smear * Blood chemistry values and urinalysis in the following ranges (Healthpoint Ranges): Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times the ULN Alanine transaminase (ALT) ≤ 2.5 times the ULN Aspartate transaminase (AST) ≤ 2.5 times the ULN Serum creatinine ≤ 1.5 times the ULN Urinalysis: WBC \< 4/HPF; RBC \< 4/HPF
Exclusion criteria
* Contraindications or known hypersensitivity to the test articles or their components. * Therapy with another investigational agent within 30 days, lower extremity angioplasty within 4 weeks, untreated osteomyelitis, or chemotherapy or radiation therapy within 5 years prior to screening. * Prior therapy of the target wound with Santyl. * Current therapy with systemic antibiotics to treat a foot ulcer, or prescription topical antibiotics on the target ulcer. * Target ulcer located over the heel (talus, distal calcaneous, navicular, or cuboid). * Fracture of bones in the target ulcer foot occurring within the past 3 months. * Cellulitis or abscess of the target ulcer foot. * A positive result from the screening Quantitative Bacteriology (Qbac) biopsy. A wound will be considered infected if the laboratory findings reveal ≥ 106 colony forming units (cfu) per gram of tissue or \> 1 beta-hemolytic Streptococcus per gram of tissue. * Target ulcer tunneling, per probing. * More than three DFU on the target foot. The target ulcer must be at least 2 cm from another ulcer. * Concomitant severe burn, immunodeficiency disorder, hematologic disorder, or malignancy (other than non-melanoma skin cancer) beyond the in situ stage. * Abnormal laboratory values that, in the opinion of the Principal Investigator, place the subject at risk for the study. * Positive serum HCG pregnancy test. * The Medical Monitor may declare any subject ineligible for a valid procedural or medical reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Wound Area | 4 Weeks | The primary efficacy endpoint was the percent change in wound area from baseline to completion of the 4-week treatment phase and the 8-week follow-up period |
Secondary
| Measure | Time frame |
|---|---|
| Number of Sharp Debridements Performed During the 4-week Treatment Phase and the 8-week Follow-up Period (12 Weeks Total) | 12 weeks |
Countries
United States
Participant flow
Recruitment details
Adults aged 18 years and older, with a diabetic foot ulcer that has not responded to treatment
Participants by arm
| Arm | Count |
|---|---|
| Collagenase Santyl Ointment Santyl : Applied an amount sufficient (thickness of a nickel) to cover the wound area. It will be applied once daily during the treatment phase, up to four weeks. | 29 |
| Vehicle (White Petrolatum) White Petrolatum : Applied an amount sufficient (thickness of a nickel) to cover the wound area. It will be applied once daily during the treatment phase, up to four weeks. | 28 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Subject non-compliance | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
| Overall Study | wound closed = deemed healed | 1 | 0 |
| Overall Study | wound size increased | 1 | 0 |
Baseline characteristics
| Characteristic | Vehicle (White Petrolatum) | Collagenase Santyl Ointment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 20 Participants | 39 Participants |
| Age Continuous | 59.9 years STANDARD_DEVIATION 12.4 | 60.0 years STANDARD_DEVIATION 9.4 | 59.9 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment United States | 28 participants | 29 participants | 57 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 23 Participants | 21 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 29 | 5 / 28 |
| serious Total, serious adverse events | 4 / 29 | 4 / 28 |
Outcome results
Primary
Change in Wound Area
The primary efficacy endpoint was the percent change in wound area from baseline to completion of the 4-week treatment phase and the 8-week follow-up period
Time frame: 4 Weeks
Population: Sample size originally set at 100 to provide 80% power, a=0.05. Interim analysis when enrollment reached 50 indicated results would not change with additional enrollment. Intent-to-treat used for primary inference; Missing values imputed by method of population mean and last observation carried forward (wound area).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Collagenase Santyl Ointment | Change in Wound Area | Follow-up Period | -49.34 percentage of average change in wound | Standard Error 12.34 |
| Collagenase Santyl Ointment | Change in Wound Area | Treatment Phase | -32.74 percentage of average change in wound | Standard Error 7.12 |
| Vehicle (White Petrolatum) | Change in Wound Area | Treatment Phase | -33.08 percentage of average change in wound | Standard Error 7.13 |
| Vehicle (White Petrolatum) | Change in Wound Area | Follow-up Period | -34.27 percentage of average change in wound | Standard Error 12.36 |
Secondary
Number of Sharp Debridements Performed During the 4-week Treatment Phase and the 8-week Follow-up Period (12 Weeks Total)
Time frame: 12 weeks
Population: Intent-to-Treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Santyl Ointment | Number of Sharp Debridements Performed During the 4-week Treatment Phase and the 8-week Follow-up Period (12 Weeks Total) | 1.38 debridements | Standard Error 0.22 |
| Vehicle (White Petrolatum) | Number of Sharp Debridements Performed During the 4-week Treatment Phase and the 8-week Follow-up Period (12 Weeks Total) | 1.5 debridements | Standard Error 0.22 |