Neuropathic Diabetic Ulcer - Foot
Conditions
Keywords
Foot Ulcer, Diabetic, Wound Healing, Integra Dermal Regeneration Template, Full Thickness, Neuropathic, Omnigraft
Brief summary
The objective of this study is to evaluate the safety and efficacy of the INTEGRA® Dermal Regeneration Template for the treatment of diabetic foot ulcers located distal to the malleolus in subjects with diabetes mellitus, neuropathy, and without significantly compromised arterial circulation.
Interventions
DEVICEIntegra® Dermal Regeneration Template
Application of Integra® Dermal Regeneration Template in diabetic foot ulcer
Conventional Wound Therapy
Sponsors
Integra LifeSciences Corporation
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
* Type I or Type II diabetes mellitus * Glycosylated hemoglobin, HbA1c, ≤ 12% * Negative serum pregnancy test at screening for female participants of child-bearing potential * Willing and able to maintain the required off-loading (as applicable for the location for the ulcer) and applicable dressing changes * At least one DFU that met the following criteria: 1. Ulcer was diagnosed as a full-thickness neuropathic DFU that was located distal to the malleolus (excluding ulcers between the toes but including those of the heel), 2. Minimum 2-cm margin between the qualifying study ulcer and any other ulcers on the specified foot (post debridement), 3. Area greater than or equal to 1 square centimeter and less than or equal to 12 square centimeters (post debridement at the time of randomization), 4. Wagner grade 1 or 2, 5. Depth less than or equal to 5 millimeters with no exposed capsule, tendon or bone and no tunneling, undermining or sinus tracts, 6. Duration of the study ulcer was at least 30 days at the time of the screening visit * Adequate vascular perfusion of the affected limb
Exclusion criteria
* Suspected or confirmed signs/symptoms of gangrene or wound infection on any part of the limb * History of hypersensitivity to bovine collagen and/or chondroitin. * Pregnancy * Previous treatment under this clinical protocol * Participation in another clinical trial involving a device or systematically administered investigational study drug or treatment within 30 days of the randomization visit. * Receiving or scheduled to receive a medication or treatment which, in the opinion of the investigator, was known to interfere with, or affect the rate and quality of wound healing * Any unstable condition or circumstance that could interfere with treatment regimen compliance * Excessive lymphedema that could interfere with wound healing * Unstable Charcot foot or Charcot with boney prominence * Ulcers secondary to a disease other than diabetes * Osteomyelitis with necrotic soft bone * Chopart amputation * History of bone cancer or metastatic disease of the affected limb, radiation therapy to the foot, or chemotherapy within the 12 months prior to randomization * Treatment with wound dressings that include growth factors, engineered tissues, or skin substitutes within 30 days of randomization or scheduled to receive such treatment during the study * Non-study ulcer requiring treatment that could not be treated during the study with moist wound therapy * History of or intercurrent illnesses or conditions (other than diabetes) that would compromise the safety of the subject, or the normal wound healing process * Employees or relatives of any member of the investigational site or sponsor * Size of the study ulcer following debridement decreased by more than 30% during the run in period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Complete Wound Closure | 16 weeks | 100% closure as assessed by the Investigator and confirmed at 2 consecutive treatment phase visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Complete Wound Closure | 16 weeks | Percentage of subjects with complete wound closure of the study ulcer, as assessed by computerized planimetry, during the treatment phase. |
| Time to Complete Wound Closure | 16 weeks | Measures the time to complete wound closure as assessed by the Investigator. |
| Rate of Wound Closure | 16 weeks | Rate of wound closure as assessed by computerized planimetry |
| Incidence of Ulcer Recurrence | 12 weeks | Measures the incidence of ulcer recurrence at the site of the study ulcer during the follow up phase. |
| Change in Short Form Health Survey (SF-36) Quality of Life Metrics | Baseline and 16 weeks | Short Form Health Survey (SF-36)- Quality of Life Metrics. The SF-36 was utilized and the Physical Function and Bodily Pain subscales were norm-based, with a Mean = 50, SD = 10. Scores could theoretically range from 0 to 100, with higher scores indicating a better health status. |
Countries
Netherlands Antilles, United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 36 medical centers between March 2010 and November 2013. The first study participant was enrolled in April 2010 and the last study participant was enrolled in November 2013.
Pre-assignment details
Participants participated in a Run-In phase that must last a minimum of 14 days, but may have been extended up to 17 days to allow for scheduling of the randomization visit.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing and a gauze wrap and, an offloading/protective device were to be used in conjunction with the IDRT. | 154 |
| Control Treatment Control Treatment consisted of moist wound therapy and was comprised of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing and a gauze wrap and, an offloading/protective device | 153 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Run In | screen failure | 0 | 238 |
Baseline characteristics
| Characteristic | Active Treatment | Control Treatment | Total |
|---|---|---|---|
| Age, Continuous | 55.8 years | 57.3 years | 56.5 years |
| Region of Enrollment Netherlands Antilles | 2 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 152 participants | 151 participants | 303 participants |
| Sex: Female, Male Female | 36 Participants | 39 Participants | 75 Participants |
| Sex: Female, Male Male | 118 Participants | 114 Participants | 232 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 154 | 0 / 153 |
| serious Total, serious adverse events | 38 / 154 | 55 / 153 |
Outcome results
Primary
Incidence of Complete Wound Closure
100% closure as assessed by the Investigator and confirmed at 2 consecutive treatment phase visits.
Time frame: 16 weeks
Population: The results were based on the Investigator assessment and ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Incidence of Complete Wound Closure | 79 participants |
| Control Treatment | Incidence of Complete Wound Closure | 49 participants |
Secondary
Change in Short Form Health Survey (SF-36) Quality of Life Metrics
Short Form Health Survey (SF-36)- Quality of Life Metrics. The SF-36 was utilized and the Physical Function and Bodily Pain subscales were norm-based, with a Mean = 50, SD = 10. Scores could theoretically range from 0 to 100, with higher scores indicating a better health status.
Time frame: Baseline and 16 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Treatment | Change in Short Form Health Survey (SF-36) Quality of Life Metrics | Physical Function | 1.28 units on a scale | Standard Deviation 11.62 |
| Active Treatment | Change in Short Form Health Survey (SF-36) Quality of Life Metrics | Bodily Pain | 2.33 units on a scale | Standard Deviation 9.42 |
| Control Treatment | Change in Short Form Health Survey (SF-36) Quality of Life Metrics | Bodily Pain | -.50 units on a scale | Standard Deviation 9.82 |
| Control Treatment | Change in Short Form Health Survey (SF-36) Quality of Life Metrics | Physical Function | -1.41 units on a scale | Standard Deviation 9.22 |
Secondary
Incidence of Complete Wound Closure
Percentage of subjects with complete wound closure of the study ulcer, as assessed by computerized planimetry, during the treatment phase.
Time frame: 16 weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Incidence of Complete Wound Closure | 50 percentage of subjects |
| Control Treatment | Incidence of Complete Wound Closure | 31 percentage of subjects |
Secondary
Incidence of Ulcer Recurrence
Measures the incidence of ulcer recurrence at the site of the study ulcer during the follow up phase.
Time frame: 12 weeks
Population: ITT Population complete wound healed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment | Incidence of Ulcer Recurrence | 15 participants |
| Control Treatment | Incidence of Ulcer Recurrence | 13 participants |
Secondary
Rate of Wound Closure
Rate of wound closure as assessed by computerized planimetry
Time frame: 16 weeks
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Rate of Wound Closure | 7.15 percentage wound closure/week | Standard Deviation 8.27 |
| Control Treatment | Rate of Wound Closure | 4.81 percentage wound closure/week | Standard Deviation 7.34 |
Secondary
Time to Complete Wound Closure
Time to complete wound closure, as assessed by computerized planimetry.
Time frame: 16 weeks
Population: ITT population complete wound healed with analyzable data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Treatment | Time to Complete Wound Closure | 43 days |
| Control Treatment | Time to Complete Wound Closure | 78 days |
Secondary
Time to Complete Wound Closure
Measures the time to complete wound closure as assessed by the Investigator.
Time frame: 16 weeks
Population: ITT Population complete wound healed with analyzable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Time to Complete Wound Closure | 52.61 days | Standard Deviation 27.22 |
| Control Treatment | Time to Complete Wound Closure | 69.78 days | Standard Deviation 31.73 |