Diabetic Foot Ulcer
Conditions
Keywords
Diabetic Foot Ulcer, Chronic wounds, Chronic ulcers, Oasis, Dermagraft, Adaptic
Brief summary
The primary objective of this study is to assess the effectiveness of cellular dermal replacement tissue vs. non-viable extracellular matrix (ECM) for the treatment of non-healing diabetic foot ulcers. Our hypothesis is that these devices are of equal efficacy.
Interventions
DEVICESECONDARY dressing gauze and tape
SECONDARY dressing gauze and tape
PROCEDUREdebridement, irrigation
debridement, irrigation
DEVICEDermagraft
Dermagraft per company protocol
DEVICEOasis
Oasis per company protocol
Sponsors
VA Northern California Health Care System
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
(Answering NO will exclude patient): * An Institutional Review Board (IRB) Informed Consent Form signed and dated prior to any study-related activities. * The area of the study ulcer after debridement is between 1 cm2 and 25 cm2 at Visit 3/Week 0. * Subjects between 18 and 85 years of age. * Subject's highest Ankle-Brachial Pressure Index (ABPI) / Ankle-Arm Index (AAI) is greater than or equal to 0.80 and lower than 1.4 (the highest ABPI/AAI value from three measurements within last 6 months shall apply).or a toe-arm index is equal to or higher than 0.6. * The patient has one or more diabetic ulcers on the target foot with only one ulcer selected as the study (target) ulcer. The target ulcer must be at least 4 cm from a non-target ulcer and in the Investigator's opinion, be unlikely to coalesce with another ulcer within 12 weeks of randomization. * Subject's study ulcer is full thickness and does not extend to bone, muscle, or tendon. * Subject's study ulcer has been present at least 4 weeks prior to the initial screening (Visit 1) or 6 weeks at randomization (Visit 3). * Subject has been diagnosed with Type 1 or Type 2 diabetes and HbA1c is less than 10%. * Study ulcer has no clinical feature of infection (2 signs of inflammation and elevated bacterial load of the wound). * For female subjects of childbearing age potential, the subject has a negative pregnancy test and is not lactating for the duration of the study. * Subject understands the requirements of this study and is willing to comply with all the study requirements.
Exclusion criteria
(Answering YES will exclude patient): * The subject is diagnosed with cancer and is undergoing treatment with immunosuppressive or chemotherapeutic agents, radiotherapy or systemic corticosteroids less than 30 days before enrollment. * The subject is diagnosed with HIV/AIDS. * The subject is diagnosed with any bleeding disorders. * The subject is diagnosed with any connective tissue diseases. * For female subjects, the subject is pregnant or lactating. * The subject has a history of illicit drug use within one year of enrollment. * In the past year, the subject experiences episodes of drinking more than 5 alcoholic beverages in less than two hours and/or drinking alcohol has become a problem in interpersonal relationships, work, driving and/or their behavior in general. * The subject has any active infected wounds or osteomyelitis (confirmed by bone biopsy, MRI or bone scan). * Doppler exam within the last 365 days demonstrating reflux greater than 0.5 seconds. * The subject is diagnosed with active Charcot as described by Saunder's classification system. * The subject manifests signs of poor nutritional status and/or albumin level \< 2.9. * The subject has been exposed to Dermagraft and/or Oasis in the last 60 days. * The study ulcer size is less than 0.5 cm2 or greater than 25 cm2. * The subject has any porcine allergy or cow product allergy. * The subject's recent (last 30 days) chemistry tests serum creatinine is 2 times above the upper limit of normal and/or LFT's 3 times above the upper limit of normal. * Between Visit 1/Week -2 and Visit 3/Week 0 (randomization) the study ulcer has decreased in size by more than 40%, or increased in size by more than 50%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wound Closure by Week 15 | 15 weeks | The primary outcome of interest is defined as the wound healed completely on or before visit 15, regardless of a later recurrence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wound Closure at 20 Weeks | 20 weeks | Complete wound closure at study endpoint. The Secondary outcome of interest is defined as the wound healed completely on or before visit 19, regardless of a later recurrence. The number of subjects analyzed at secondary outcome differs from primary outcome due to some subjects not completing the study. |
| Cost Effectiveness | 12 weeks | — |
Countries
United States
Participant flow
Recruitment details
120 subjects enrolled from which 2 study subjects were not randomized into any groups and were terminated from the study; therefore, we only had overall of 118 study subjects.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Consist of subjects who were randomized to treatment with standard of Care (SOC) which included debridement, irritation, primary dressing, Adaptic, secondary dressing gauze and tape. | 28 |
| Dermagraft Study subjects who were randomized to treatment arm with Dermagraft. Dermagraft is a cryopreserved human fibroblast-derived dermal substitute composed of viable newborn foreskin fibroblasts, seeded onto a bio-absorbable polyglactin mesh.
The treatment included debridement, irrigation, primary dressing and Dermagraft and Adaptic, and secondary dressing with gauze and tape.
Dermagraft placed per company protocol | 42 |
| Oasis Study subjects who were randomized to treatment arm with Oasis. Oasis is a bio-absorbable ECM derived from porcine small intestinal submucosa. the product is processed using proprietary methods to retain its original structure while stored at room temperature.
The treatment included debridement, irrigation, primary dressing and Oasis and Adaptic, and secondary dressing with gauze and tape.
Oasis placed per company protocol | 48 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Screen failure, loss to follow-up | 2 | 7 | 6 |
Baseline characteristics
| Characteristic | Standard of Care | Dermagraft | Oasis | Total |
|---|---|---|---|---|
| Age, Customized | 63.31 years STANDARD_DEVIATION 9.09 | 62.83 years STANDARD_DEVIATION 9.3 | 61.88 years STANDARD_DEVIATION 8.64 | 62.67 years STANDARD_DEVIATION 9.01 |
| BMI | 36.52 kg/m2 STANDARD_DEVIATION 6.59 | 32.44 kg/m2 STANDARD_DEVIATION 5.32 | 36.51 kg/m2 STANDARD_DEVIATION 11.55 | 35.15 kg/m2 STANDARD_DEVIATION 7.83 |
| Ethnicity (NIH/OMB) Analyzed participants Hispanic or Latino | 0 Participants | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Analyzed participants Not Hispanic or Latino | 28 Participants | 39 Participants | 44 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Analyzed participants Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Analyzed participants American Indian or Alaska Native | 2 Participants | 0 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) Analyzed participants Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Analyzed participants Black or African American | 2 Participants | 1 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) Analyzed participants More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Analyzed participants Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Analyzed participants Unknown or Not Reported | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) Analyzed participants White | 21 Participants | 37 Participants | 33 Participants | 91 Participants |
| Region of Enrollment United States | 28 Participants | 42 Participants | 48 Participants | 118 Participants |
| Sex: Female, Male Analyzed participants Female | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Analyzed participants Male | 26 Participants | 42 Participants | 47 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 28 | 6 / 42 | 10 / 48 |
| other Total, other adverse events | 3 / 28 | 4 / 42 | 2 / 48 |
| serious Total, serious adverse events | 6 / 28 | 15 / 42 | 16 / 48 |
Outcome results
Primary
Wound Closure by Week 15
The primary outcome of interest is defined as the wound healed completely on or before visit 15, regardless of a later recurrence.
Time frame: 15 weeks
Population: Primary Outcome results consist of data available for the Northern California Veteran patient population participants who completed the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care | Wound Closure by Week 15 | Not Healed | 10 Participants |
| Standard of Care | Wound Closure by Week 15 | Healed completely | 16 Participants |
| Dermagraft | Wound Closure by Week 15 | Healed completely | 20 Participants |
| Dermagraft | Wound Closure by Week 15 | Not Healed | 15 Participants |
| Oasis | Wound Closure by Week 15 | Healed completely | 33 Participants |
| Oasis | Wound Closure by Week 15 | Not Healed | 9 Participants |
p-value: 0.051795% CI: [0.9141, 8.4839]Fisher Exact
Secondary
Cost Effectiveness
Time frame: 12 weeks
Population: Data not available because the investigators did not asses the cost effectiveness for the study.
Secondary
Wound Closure at 20 Weeks
Complete wound closure at study endpoint. The Secondary outcome of interest is defined as the wound healed completely on or before visit 19, regardless of a later recurrence. The number of subjects analyzed at secondary outcome differs from primary outcome due to some subjects not completing the study.
Time frame: 20 weeks
Population: Primary Outcome results consist of data still available for the Veteran patient population participants who completed the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care | Wound Closure at 20 Weeks | Not healed | 5 Wound Closure in weeks |
| Standard of Care | Wound Closure at 20 Weeks | Healed completely | 18 Wound Closure in weeks |
| Dermagraft | Wound Closure at 20 Weeks | Not healed | 9 Wound Closure in weeks |
| Dermagraft | Wound Closure at 20 Weeks | Healed completely | 25 Wound Closure in weeks |
| Oasis | Wound Closure at 20 Weeks | Not healed | 12 Wound Closure in weeks |
| Oasis | Wound Closure at 20 Weeks | Healed completely | 27 Wound Closure in weeks |
p-value: 0.797495% CI: [0.2543, 2.5224]Fisher Exact