Diabetic Foot Ulcer
Conditions
Brief summary
The study will evaluate the efficacy of PriMatrix Dermal Repair Scaffold in the management of diabetic foot ulcers in subjects with diabetes mellitus versus the Standard of Care treatment. Half of patients will be treated using PriMatrix while the other half will receive Standard of Care treatment.
Detailed description
A diabetic foot ulcer (DFU) is a major health complication that affects up to 15% of individuals with diabetes mellitus over their lifetime. The treatment of DFUs is extremely challenging as these ulcers may not respond to standard of care (SC) treatment and frequently become infected. Advanced wound therapies like PriMatrix have become an important strategy in the treatment of hard-to-heal chronic DFUs by trapping and binding the patients' own cells to rebuild the dermis layer of the skin to aid in healing. The study will evaluate the efficacy of PriMatrix Dermal Repair Scaffold in the closure of DFUs in subjects with diabetes mellitus in comparison to Standard of Care treatment.
Interventions
DEVICEPriMatrix Dermal Repair Scaffold
Application of PriMatrix to ulcer
DEVICESecondary Dressings
Dressings to ensure moist wound environment
DEVICEOffloading device
Offloading device to decrease pressure to wound area
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
Subjects are required to meet all of the following criteria for enrollment into the study and subsequent randomization: 1. The subject has signed and dated an informed consent form. 2. In the opinion of the investigator, subject is able and willing to comply with study procedures, including study visits, study dressing regimens and compliance with study required off-loading device. 3. The subject is ≥ 18 years of age. 4. The subject, if female of child-bearing potential, must not be pregnant. To document pregnancy status, subject statement is acceptable. 5. The subject has Type I or Type II diabetes mellitus with investigator-confirmed glycosylated hemoglobin (HbA1c) of ≤ 12% within 3 months prior to screening visit. 6. The subject has at least one diabetic foot ulcer that meets ALL of the following criteria: * Ulcer which has been in existence for a minimum of two weeks, prior to signing the Informed Consent Form for trial participation. * Ulcer is a partial or full thickness diabetic foot ulcer without capsule/tendon/bone exposure. * Ulcer does not have tunneling, undermining, or sinus tracts that necessitates surgical OR debridement and/or penetrates to capsule/tendon/bone. * Ulcer is located on the foot or ankle (with no portion above the top of the malleolus). * Ulcer size (area) is \> 1 cm2 and \< 12 cm2 post-debridement. 7. There is a minimum 1 cm margin between the qualifying study ulcer and any other ulcer on that same foot, post-debridement. • If the subject has more than one ulcer that meets the eligibility criteria, the ulcer designated as the study ulcer will be at the discretion of the investigator. 8. The subject has adequate vascular perfusion of the affected limb as defined by at least one of the following: * Ankle-Brachial Index (ABI) ≥ 0.65 or ≤1.2, performed within 3 months of screening, * Toe pressure (plethysmography) \> 50 mmHg at time of screening, * TcPO2 \> 40 mmHg at time of screening 9. The subject or responsible caregiver is willing and able to maintain required applicable dressing changes as well as study required off-loading/protective device for the duration of the study.
Exclusion criteria
Subjects will not be enrolled in the study if any of the following criteria are met: 1. The subject was previously randomized and treated under this clinical study protocol. 2. The subject has suspected or confirmed gangrene or ulcer infection of the study ulcer or receiving systemic antibiotics for the treatment of such. 3. The subject has suspected or confirmed osteomyelitis of the foot with the study ulcer. 4. The subject has a history of hypersensitivity to bovine collagen, as determined by prior medical history. Protocol Number: T-PMXDFU-01 Confidential Page 23 of 64 Version 5.0 06 Nov 2018 5. The subject has participated in another clinical trial involving a device or a systemically administered investigational study drug/treatment within 28 days of randomization. 6. The subject has received, within 28 of signing Informed Consent Form, or is scheduled to receive during study participation, a medication or treatment which is known to interfere with or affect the rate and quality of ulcer healing (e.g., systemic steroids, immunosuppressive therapy, autoimmune disease therapy, dialysis, radiation therapy to the foot, vascular surgery, angioplasty, or thrombolysis). 7. The subject has a history of bone cancer or metastatic disease of the affected limb, radiation therapy to the foot, or has had chemotherapy within the 12 months prior to signing Informed Consent Form for trial participation. 8. In the opinion of the investigator, the subject has a history of, or is currently diagnosed with, any illness or condition, other than diabetes, that could interfere with ulcer healing (e.g., end-stage renal disease, severe malnutrition, liver disease, aplastic anemia, connective tissue disorder, acquired immune deficiency syndrome, HIV positive, or sickle cell anemia). 9. In the opinion of the investigator, the subject has unstable Charcot foot or Charcot with bony prominence that could inhibit ulcer healing. 10. The subject has ulcers secondary to a disease other than diabetes (e.g., vasculitis, neoplasms, or hematological disorders). 11. In the opinion of the investigator, the subject has excessive lymphedema that could interfere with off-loading and/or ulcer healing. 12. The study ulcer has received ulcer dressings that included growth factors, engineered tissues, or skin substitutes within 28 days of randomization or is scheduled to receive treatment during the study (e.g., Regranex, Dermagraft, Apligraf, EpiFix, GraftJacket, OASIS, Omnigraft, or Integra BMWD). 13. At the end of the screening phase and based on planimetric assessment, the area of the study ulcer after sharp debridement has decreased by more than 30% over the two-week screening period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Complete Wound Closure, as Assessed by the Investigator, at or Before Week 12 of the Treatment Phase | 12-week Treatment Phase | Complete wound closure was defined as 100% re-epithelialization of the ulcer surface without detectable exudate, confirmed on 2 consecutive study visits 1 week apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Complete Wound Closure, as Assessed by Computerized Planimetry, at or Before Week 12 of the Treatment Phase | 12-week treatment phase | — |
| Time to Complete Wound Closure, as Assessed by the Investigator | 12-week Treatment Phase | — |
| Time to Complete Wound Closure, as Assessed by Computerized Planimetry. | 12-week Treatment Phase | — |
| Rate of Wound Closure, as Assessed by Computerized Planimetry. | Weeks 1-12 during Treatment Phase | Rate of Wound closure was recorded as the percentage of the wound that was closed, per week. NOTE1: Rate (% closed/week) = 7 \* \[(Baseline wound size) - (Post-baseline wound size)\]/\[(Baseline wound size) \* (days in trial)\] NOTE2: Missing data is imputed using LOCF method for this analysis |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PriMatrix Arm will receive PriMatrix Dermal Repair Scaffold plus secondary dressings to maintain a moist wound healing environment and an appropriate off-loading device.
PriMatrix Dermal Repair Scaffold: Application of PriMatrix to ulcer
Secondary Dressings: Dressings to ensure moist wound environment
Offloading device: Offloading device to decrease pressure to wound area | 103 |
| Standard of Care Arm will receive moist wound therapy consisting of 0.9% Sodium Chloride gel plus secondary dressings and an appropriate off-loading device.
Secondary Dressings: Dressings to ensure moist wound environment
Offloading device: Offloading device to decrease pressure to wound area | 104 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 9 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other Reason | 5 | 7 |
| Overall Study | Physician Decision | 2 | 4 |
| Overall Study | Sponsor requested withdrawal | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 6 |
Baseline characteristics
| Characteristic | PriMatrix | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 58.5 Years STANDARD_DEVIATION 11.92 | 57.6 Years STANDARD_DEVIATION 11.49 | 58.0 Years STANDARD_DEVIATION 11.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 31 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 73 Participants | 133 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 26 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 81 Participants | 74 Participants | 155 Participants |
| Region of Enrollment United States | 103 participants | 104 participants | 207 participants |
| Sex: Female, Male Female | 20 Participants | 24 Participants | 44 Participants |
| Sex: Female, Male Male | 83 Participants | 80 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 110 | 0 / 116 |
| other Total, other adverse events | 16 / 110 | 23 / 116 |
| serious Total, serious adverse events | 19 / 110 | 15 / 116 |
Outcome results
Primary
Percentage of Subjects With Complete Wound Closure, as Assessed by the Investigator, at or Before Week 12 of the Treatment Phase
Complete wound closure was defined as 100% re-epithelialization of the ulcer surface without detectable exudate, confirmed on 2 consecutive study visits 1 week apart.
Time frame: 12-week Treatment Phase
Population: Primary Efficacy Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PriMatrix | Percentage of Subjects With Complete Wound Closure, as Assessed by the Investigator, at or Before Week 12 of the Treatment Phase | 47 Participants |
| Standard of Care | Percentage of Subjects With Complete Wound Closure, as Assessed by the Investigator, at or Before Week 12 of the Treatment Phase | 29 Participants |
Secondary
Percentage of Subjects With Complete Wound Closure, as Assessed by Computerized Planimetry, at or Before Week 12 of the Treatment Phase
Time frame: 12-week treatment phase
Population: Primary Efficacy Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PriMatrix | Percentage of Subjects With Complete Wound Closure, as Assessed by Computerized Planimetry, at or Before Week 12 of the Treatment Phase | 36 Participants |
| Standard of Care | Percentage of Subjects With Complete Wound Closure, as Assessed by Computerized Planimetry, at or Before Week 12 of the Treatment Phase | 20 Participants |
Secondary
Rate of Wound Closure, as Assessed by Computerized Planimetry.
Rate of Wound closure was recorded as the percentage of the wound that was closed, per week. NOTE1: Rate (% closed/week) = 7 \* \[(Baseline wound size) - (Post-baseline wound size)\]/\[(Baseline wound size) \* (days in trial)\] NOTE2: Missing data is imputed using LOCF method for this analysis
Time frame: Weeks 1-12 during Treatment Phase
Population: Primary Efficacy Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 1 | 1.727 Percentage of Wound Closed/Week | Standard Deviation 7.142 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 2 | 1.722 Percentage of Wound Closed/Week | Standard Deviation 9.446 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 3 | 2.587 Percentage of Wound Closed/Week | Standard Deviation 10.082 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 4 | 3.443 Percentage of Wound Closed/Week | Standard Deviation 9.376 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 5 | 3.603 Percentage of Wound Closed/Week | Standard Deviation 9.371 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 6 | 3.764 Percentage of Wound Closed/Week | Standard Deviation 9.441 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 7 | 4.054 Percentage of Wound Closed/Week | Standard Deviation 9.402 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 8 | 4.017 Percentage of Wound Closed/Week | Standard Deviation 9.759 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 9 | 4.213 Percentage of Wound Closed/Week | Standard Deviation 9.554 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 10 | 3.970 Percentage of Wound Closed/Week | Standard Deviation 10.23 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 11 | 4.558 Percentage of Wound Closed/Week | Standard Deviation 9.48 |
| PriMatrix | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 12 | 4.637 Percentage of Wound Closed/Week | Standard Deviation 9.513 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 11 | 3.837 Percentage of Wound Closed/Week | Standard Deviation 10.186 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 1 | 0.996 Percentage of Wound Closed/Week | Standard Deviation 8.222 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 7 | 3.308 Percentage of Wound Closed/Week | Standard Deviation 10.072 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 2 | 1.999 Percentage of Wound Closed/Week | Standard Deviation 9.366 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 10 | 3.896 Percentage of Wound Closed/Week | Standard Deviation 10.184 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 3 | 2.524 Percentage of Wound Closed/Week | Standard Deviation 9.304 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 8 | 3.632 Percentage of Wound Closed/Week | Standard Deviation 10.115 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 4 | 2.990 Percentage of Wound Closed/Week | Standard Deviation 9.653 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 12 | 3.928 Percentage of Wound Closed/Week | Standard Deviation 10.263 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 5 | 3.476 Percentage of Wound Closed/Week | Standard Deviation 9.549 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 9 | 3.820 Percentage of Wound Closed/Week | Standard Deviation 10.184 |
| Standard of Care | Rate of Wound Closure, as Assessed by Computerized Planimetry. | Week 6 | 3.279 Percentage of Wound Closed/Week | Standard Deviation 9.951 |
Secondary
Time to Complete Wound Closure, as Assessed by Computerized Planimetry.
Time frame: 12-week Treatment Phase
Population: Primary Efficacy Population with Complete Wound Closure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PriMatrix | Time to Complete Wound Closure, as Assessed by Computerized Planimetry. | 51.8 days | Standard Deviation 20.63 |
| Standard of Care | Time to Complete Wound Closure, as Assessed by Computerized Planimetry. | 56.8 days | Standard Deviation 16.25 |
Secondary
Time to Complete Wound Closure, as Assessed by the Investigator
Time frame: 12-week Treatment Phase
Population: Primary Efficacy Population with Complete Wound Closure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PriMatrix | Time to Complete Wound Closure, as Assessed by the Investigator | 53.6 days | Standard Deviation 21.39 |
| Standard of Care | Time to Complete Wound Closure, as Assessed by the Investigator | 56.2 days | Standard Deviation 18.24 |