Third Degree Burn, Burns, Wound Infection, Degloving Injury
Conditions
Keywords
Complex skin defects, Burns, Wound infection, Skin trauma
Brief summary
This pilot Phase I/II clinical study will be conducted at up to three clinical sites. This is an open-label, randomized, comparative study with a maximum of fifteen (15) patients, each with skin defects. The patients are intended to undergo sequential surgical procedures involving surgical skin debridement and temporary allogeneic (cadaver skin) grafting at various separate or contiguous wound sites. Patients will be randomized within each wound site to one of two test products: cadaver skin or StrataGraft™ skin tissue.
Detailed description
Stratatech has completed a phase I/IIa clinical study to assess the safety and efficacy of escalating amounts of StrataGraft skin tissue in patients with complex skin defects requiring sequential debridement and temporary wound coverage with biological dressing prior to autografting. The specific objectives of this phase I/IIa clinical trial were to assess the safety of StrataGraft skin tissue using a predetermined panel of clinical and laboratory endpoints and assess the efficacy of StrataGraft skin tissue by comparing the ability of StrataGraft skin tissue to the standard of care, human cadaver skin, to condition complex skin defects for subsequent autografting. In three cohorts of five patients each, the maximum amount of StrataGraft skin tissue applied to excised full-thickness skin wounds was increased sequentially from 0.5% to 1.0%, and then to 1.5% TBSA. Equivalent study wound areas on each subject were treated with StrataGraft or cadaver allograft for one week, at which time the allograft tissues were removed and the wound bed was evaluated. Infection and appearance of the temporary allogeneic skin tissue were evaluated at every study session until autograft placement. The wound was covered with split-thickness skin autografts when the wound was judged ready to accept an autograft. Autograft take was assessed two weeks after autograft placement.
Interventions
BIOLOGICALStrataGraft Skin Tissue
StrataGraft™ skin tissue is provided as a suturable circular patch of stratified epithelial tissue composed of a living dermal matrix (containing dermal fibroblasts) overlaid with human epidermal cells (NIKS™ cells).
PROCEDURECadaver allograft
The standard of care for temporary coverage of full thickness skin defects is coverage with cadaver allograft until the wound can be autografted.
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Stratatech, a Mallinckrodt Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged greater than 18 yrs. * Patients with complex skin defects requiring sequential debridement under anesthesia with temporary biological dressing (allogeneic grafting) prior to autografting * Full-thickness skin defects * Informed consent
Exclusion criteria
* Prisoners * Pregnant (positive urinary pregnancy in women of child-bearing potential at Visit#1) or lactating females * Immunosuppressive therapy * Infection with Human Immunodeficiency Virus * Venous stasis ulcers of the lower leg * Diabetic foot ulcers * Donor site wounds * Wounds of less than 5% body surface area * Wounds of the hands, face, and feet (although such wound surface areas can be counted toward total injured BSA) * Prior entry into this study * Expected survival of less than 3 months * Concomitant processes sustained contemporaneously with the dermal injury (e.g., inhalational injury requiring ventilation, electrical injury with cardiac damage or arrhythmia, sepsis, other serious or unstabilized organ damage from trauma, etc.) * Use of an investigational agent within 30 days * Active malignancy * Clinical evidence of malnutrition * Clinically significant renal, hepatic, cardiac, pulmonary, or neurological impairments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Autograft Take on Wounds Prepared by StrataGraft™ Skin Tissue. | two weeks post-autografting | The percentage take of the autografted area on each treatment site based on clinical judgement of visual and tactile assessments two weeks after autografting of wounds that had been temporarily covered with StrataGraft skin tissue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Appearance of Allograft Tissues | StrataGraft and cadaver allograft appearance were performed every other day after placement and at the time of allograft removal and the values averaged for each subject. | The following three point scale was used to assess the condition of skin allografts: pink and adherent (2 points); either pink or adherent but not both (1 point); or neither pink nor adherent (0 points). |
| Viability of Allograft Tissues | At the time of allograft removal (~7 days) | Immunohistochemical staining for Ki67, a protein expressed only in proliferating cells. |
Countries
United States
Participant flow
Recruitment details
The study evaluated autograft take and infection in 15 patients with full-thickness skin defects who required sequential surgical procedures. Subjects had surgical excision and temporary placement of StrataGraft and cadaver allograft. The trial was conducted at the University of Wisconsin Hospital and the Arizona Burn Center.
Pre-assignment details
All subjects were treated with both StrataGraft and cadaver allograft in a split-wound design. The half-wound sites were randomized to receive StrataGraft or cadaver allograft.
Participants by arm
| Arm | Count |
|---|---|
| StrataGraft : Cadaver Allograft Wounds were excised and the half-wound sites were randomized to receive StrataGraft skin tissue or cadaver allograft for 7 days until the wounds were ready for autografting. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | StrataGraft : Cadaver Allograft |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 43.4 years STANDARD_DEVIATION 14.7 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
Percent Autograft Take on Wounds Prepared by StrataGraft™ Skin Tissue.
The percentage take of the autografted area on each treatment site based on clinical judgement of visual and tactile assessments two weeks after autografting of wounds that had been temporarily covered with StrataGraft skin tissue.
Time frame: two weeks post-autografting
Population: Intrapatient treatment sites were randomized such that each half of the wound site received StrataGraft and the other half received cadaver skin. Therefore, each patient received StrataGraft and cadaver allograft.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| StrataGraft Skin Tissue | Percent Autograft Take on Wounds Prepared by StrataGraft™ Skin Tissue. | 97.7 Percent Area of Autograft Take (%) | Standard Deviation 6.78 |
| Cadaver Skin | Percent Autograft Take on Wounds Prepared by StrataGraft™ Skin Tissue. | 96.7 Percent Area of Autograft Take (%) | Standard Deviation 10.47 |
Secondary
Appearance of Allograft Tissues
The following three point scale was used to assess the condition of skin allografts: pink and adherent (2 points); either pink or adherent but not both (1 point); or neither pink nor adherent (0 points).
Time frame: StrataGraft and cadaver allograft appearance were performed every other day after placement and at the time of allograft removal and the values averaged for each subject.
Population: Treatment for each patient was randomized such that each half of the wound site received StrataGraft or cadaver skin. Therefore, each patient received StrataGraft and cadaver allograft.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| StrataGraft Skin Tissue | Appearance of Allograft Tissues | 1.70 points | Standard Error 0.62 |
| Cadaver Skin | Appearance of Allograft Tissues | 1.49 points | Standard Error 0.65 |
Secondary
Viability of Allograft Tissues
Immunohistochemical staining for Ki67, a protein expressed only in proliferating cells.
Time frame: At the time of allograft removal (~7 days)
Population: Treatment for each patient was randomized such that each half of the wound site received StrataGraft or cadaver skin. Therefore, each patient received StrataGraft and cadaver allograft.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| StrataGraft Skin Tissue | Viability of Allograft Tissues | 0.567 Ki67 positive cells/ total cells | Full Range 0.175 |
| Cadaver Skin | Viability of Allograft Tissues | 0.189 Ki67 positive cells/ total cells | Full Range 0.315 |