Diabetic Foot Ulcers
Conditions
Brief summary
The purpose of this study is to assess the mechanism of action of the Unite Biomatrix and compare its performance with the standard of care, saline moistened gauze, for the treatment of diabetic foot ulcers.
Interventions
DEVICEUnite Biomatrix
Collagen based, decellularized equine pericardial dressing for skin surface wounds
OTHERSaline and Gauze
gauze moistened with sterile saline
Sponsors
Synovis Surgical Innovations
Baxter Healthcare 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
1. A full thickness diabetic foot ulcer with a viable wound bed free of necrotic material (grade 1 on Wagner scale). 2. Diagnosis of diabetes mellitus (type I or II) adequately controlled. 3. The ulcer is greater than 4 weeks duration. 4. Three or fewer ulcers separated by \> 3.0 cm distance. 5. Post-debridement, the ulcer size must be between 1 and 10 sq cm2. 6. Ankle/brachial index is between 0.7 to 1.2 and or one of the following must be present: * transcutaneous partial pressure oxygen (TcPO2) \> 30 mmHg at the ankle * toe pressure of \>40mm Hg or a Doppler waveform consistent with adequate flow in the foot (biphasic or triphasic) 7. At least 18 years old. 8. Able and willing to provide a voluntary written informed consent. 9. Able and willing to wear an off-loading orthopedic shoe. 10. Able and willing to attend scheduled follow-up visits and study related exams.
Exclusion criteria
1. Greater than 30% reduction in wound size during first week of observation by the investigator. 2. Ulcer with exposed tendon or bone. 3. Gross clinical infection at the study ulcer site including cellulitis and osteomyelitis. 4. Gangrene. 5. Active Charcot's disease as determined by clinical and radiographic examination. 6. Ulcer of a non-diabetic pathophysiology (e.g., rheumatoid, radiation-related, and vasculitis related ulcers). 7. Known severe anemia. 8. Known serum albumin \< 2.5. 9. Renal failure with Creatinine \> 2.5. 10. Rheumatoid arthritis (and other collagen vascular disease), vasculitis, sickle cell disease, HIV. 11. Severe liver disease as defined by the treating physician or patient's primary care physician. 12. Malignancy at or near the ulcer site. 13. Any condition judged by the investigator that would cause the study to be detrimental to the patient. 14. Presence of a hematology, clinical, chemistry or other test obtained within 7 days of screening that is outside the normal range for the laboratory and is determined to be clinically significant by the investigator. 15. Received another investigational device or drug within 30 days of Day 0. 16. Radiation therapy, chemotherapy or immunosuppressive therapy within 30 days of enrollment. 17. Received another allograft, autograft or xenograft within 30 days of the Day 0. 18. Known allergy to equine derived tissue. 19. Alcohol or drug abuse, defined as current medical treatment for substance abuse. 20. Pregnant or nursing women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Not Healed by Number of Days After Procedure | Day 20, Day 40, Day 60, Day 80 | Time to complete healing was captured by Kaplan-Meier Plot showing percentage of participants not healed by number of days after procedure. Patients were considered healed at their first follow-up visit where the patient's would had healed. |
| Percentage of Participants With Wounds Healed at 12 Weeks | Week 12 | — |
| Wound Healing Pathway Markers | Day 0, 72 hours post-procedure, Week 1, Week 2, Week 4 | — |
| Bacterial Burden | Day 0, Week 1 - Week 12 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Device Failures | Week 1 to Week 24 | Includes failure to heal the ulcer by the 12-week visit under the Intent-to-Treat principle. |
| Percentage Mean of Original Wound Size From Baseline by Week | Day 0, Week 4, Week 8, Week 12 | The percent of original wound size was calculated using the following formula: measure at baseline minus measure at follow-up visit divided by measure at baseline. In cases when the baseline depth was reported as 0cm, the minimum non-zero value in the sample (0.1cm) was imputed so a percent reduction measure could be calculated. |
| Ease of Dressing Use | Week 1 to Week 12 | Ease of usage on a 5-point scale where 1=greatest ease of use and 5=greatest difficult |
| Number of Device Removals | Week 1 to Week 24 | Device removal is included in device failure under ITT. Subjects who experienced procedure-related events were also device failures under ITT. This endpoint is equivalent to device failure rates reported above. |
| Number of Participants With Ulcer Recurrence | Week 1 to Week 24 | — |
| Number of Device-related Adverse Events (AE) | Week 1 to Week 24 | — |
| Number of Procedure-related Adverse Events (AE) | Week 1 to Week 24 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Biologic - Unite Biomatrix Unite Biomatrix: Collagen based, decellularized equine pericardial dressing for skin surface wounds | 42 |
| Saline and Gauze Saline and Gauze: gauze moistened with sterile saline | 48 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Other | 2 | 5 |
| Overall Study | Physician Decision | 5 | 7 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Biologic - Unite Biomatrix | Saline and Gauze | Total |
|---|---|---|---|
| Age, Continuous | 58.1 Years STANDARD_DEVIATION 10.7 | 54.9 Years STANDARD_DEVIATION 10.2 | 56.39 Years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized Black | 11 Participants | 19 Participants | 30 Participants |
| Race/Ethnicity, Customized Caucasian | 24 Participants | 24 Participants | 48 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 10 Participants | 14 Participants | 24 Participants |
| Sex: Female, Male Male | 32 Participants | 34 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 42 | 2 / 48 |
| other Total, other adverse events | 6 / 42 | 7 / 48 |
| serious Total, serious adverse events | 9 / 42 | 8 / 48 |
Outcome results
Primary
Bacterial Burden
Time frame: Day 0, Week 1 - Week 12
Population: Source document notes no data provided. Limited information available since product no longer licensed with Baxter.
Primary
Percentage of Participants Not Healed by Number of Days After Procedure
Time to complete healing was captured by Kaplan-Meier Plot showing percentage of participants not healed by number of days after procedure. Patients were considered healed at their first follow-up visit where the patient's would had healed.
Time frame: Day 20, Day 40, Day 60, Day 80
Population: Intent-to-Treat (ITT): all randomized participants who provided consent..
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biologic - Unite Biomatrix | Percentage of Participants Not Healed by Number of Days After Procedure | Day 20 | 0.97 Percentage of Participants |
| Biologic - Unite Biomatrix | Percentage of Participants Not Healed by Number of Days After Procedure | Day 40 | 0.91 Percentage of Participants |
| Biologic - Unite Biomatrix | Percentage of Participants Not Healed by Number of Days After Procedure | Day 60 | 0.74 Percentage of Participants |
| Biologic - Unite Biomatrix | Percentage of Participants Not Healed by Number of Days After Procedure | Day 80 | 0.61 Percentage of Participants |
| Saline and Gauze | Percentage of Participants Not Healed by Number of Days After Procedure | Day 80 | 0.65 Percentage of Participants |
| Saline and Gauze | Percentage of Participants Not Healed by Number of Days After Procedure | Day 20 | 1.0 Percentage of Participants |
| Saline and Gauze | Percentage of Participants Not Healed by Number of Days After Procedure | Day 60 | 0.74 Percentage of Participants |
| Saline and Gauze | Percentage of Participants Not Healed by Number of Days After Procedure | Day 40 | 0.95 Percentage of Participants |
Primary
Percentage of Participants With Wounds Healed at 12 Weeks
Time frame: Week 12
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biologic - Unite Biomatrix | Percentage of Participants With Wounds Healed at 12 Weeks | Healed | 42.9 Percentage of participants |
| Biologic - Unite Biomatrix | Percentage of Participants With Wounds Healed at 12 Weeks | Not Healed | 57.1 Percentage of participants |
| Saline and Gauze | Percentage of Participants With Wounds Healed at 12 Weeks | Healed | 29.2 Percentage of participants |
| Saline and Gauze | Percentage of Participants With Wounds Healed at 12 Weeks | Not Healed | 70.8 Percentage of participants |
Primary
Wound Healing Pathway Markers
Time frame: Day 0, 72 hours post-procedure, Week 1, Week 2, Week 4
Population: Source document notes no data provided. Limited information available since product no longer licensed with Baxter.
Secondary
Ease of Dressing Use
Ease of usage on a 5-point scale where 1=greatest ease of use and 5=greatest difficult
Time frame: Week 1 to Week 12
Population: ITT. Note: Limited information available since product no longer licensed with Baxter. The only stats analysis information available provides data for Unite Biomatrix treatment arm, and will need to assume analysis was not performed for control arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Biologic - Unite Biomatrix | Ease of Dressing Use | Ease of Preparation | 1.4 Score on a Scale | Standard Deviation 0.6 |
| Biologic - Unite Biomatrix | Ease of Dressing Use | Handling | 1.2 Score on a Scale | Standard Deviation 0.6 |
| Biologic - Unite Biomatrix | Ease of Dressing Use | Comfortability | 1.5 Score on a Scale | Standard Deviation 0.7 |
| Biologic - Unite Biomatrix | Ease of Dressing Use | Securability | 1.4 Score on a Scale | Standard Deviation 0.6 |
Secondary
Number of Device Failures
Includes failure to heal the ulcer by the 12-week visit under the Intent-to-Treat principle.
Time frame: Week 1 to Week 24
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biologic - Unite Biomatrix | Number of Device Failures | 24 Devices |
| Saline and Gauze | Number of Device Failures | 34 Devices |
Secondary
Number of Device-related Adverse Events (AE)
Time frame: Week 1 to Week 24
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biologic - Unite Biomatrix | Number of Device-related Adverse Events (AE) | 0 Events |
| Saline and Gauze | Number of Device-related Adverse Events (AE) | 0 Events |
Secondary
Number of Device Removals
Device removal is included in device failure under ITT. Subjects who experienced procedure-related events were also device failures under ITT. This endpoint is equivalent to device failure rates reported above.
Time frame: Week 1 to Week 24
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biologic - Unite Biomatrix | Number of Device Removals | 24 Devices |
| Saline and Gauze | Number of Device Removals | 34 Devices |
Secondary
Number of Participants With Ulcer Recurrence
Time frame: Week 1 to Week 24
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Biologic - Unite Biomatrix | Number of Participants With Ulcer Recurrence | 0 Participants |
| Saline and Gauze | Number of Participants With Ulcer Recurrence | 2 Participants |
Secondary
Number of Procedure-related Adverse Events (AE)
Time frame: Week 1 to Week 24
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biologic - Unite Biomatrix | Number of Procedure-related Adverse Events (AE) | 2 Events |
| Saline and Gauze | Number of Procedure-related Adverse Events (AE) | 0 Events |
Secondary
Percentage Mean of Original Wound Size From Baseline by Week
The percent of original wound size was calculated using the following formula: measure at baseline minus measure at follow-up visit divided by measure at baseline. In cases when the baseline depth was reported as 0cm, the minimum non-zero value in the sample (0.1cm) was imputed so a percent reduction measure could be calculated.
Time frame: Day 0, Week 4, Week 8, Week 12
Population: ITT
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Length | 0.879 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Width | 0.809 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Depth | 0.820 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Area | 0.807 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Length | 0.705 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Width | 0.650 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Depth | 1.612 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Area | 0.546 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Length | 0.381 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Width | 0.323 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Depth | 0.304 Percentage mean of wound size |
| Biologic - Unite Biomatrix | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Area | 0.341 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Depth | 1.347 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Length | 0.754 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Depth | 1.365 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Width | 0.750 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Width | 0.465 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Depth | 1.082 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Area | 0.592 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 4 Area | 0.732 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Area | 0.433 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Length | 0.695 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 12 Length | 0.567 Percentage mean of wound size |
| Saline and Gauze | Percentage Mean of Original Wound Size From Baseline by Week | Week 8 Width | 0.671 Percentage mean of wound size |