Wound Healing and Scar Quality Following Mohs Surgery and Excisional Dermatologic Surgery
Conditions
Brief summary
The purpose of this research study is to test whether it is better to allow patients with post- operative wounds on the legs to heal on their own without a covering or to use a porcine xenograft (skin graft that is made from pig cells) to cover the wound during healing. It is currently not known which option is better in terms of the appearance, complication rate or the impact on the patient's quality of life during the healing process. In this location, it is common receive either treatment.
Detailed description
Porcine xenograft has been used as a barrier to the skin for over 30 years, and due to its wound healing promoting factors, we believe that its use may result in decreased healing time, smaller scar size, better cosmetic outcomes, lower pain levels, and decreased rates of infection and other post-surgical complications. Upon completion of dermatologic surgery following standard procedures, patients will be randomized into one of two groups (porcine xenograft placement or second intention healing). Weekly follow-up via questionnaires will be conducted as well as a final office visit follow-up at 3 months. The application of porcine xenograft dressings for wound healing was first studied in 1985, with evidence supporting several benefits when compared to traditional dressings \[1\]. Subsequent studies have substantiated the use of this dressing for a variety of clinical settings \[2,3\]. The EZ-DERM™ porcine xenograft is a biosynthetic dressing made from porcine collagen containing aldehyde crosslinking \[1,3\]. It has been most commonly applied to the management of 2nd degree burns, both partial-thickness and full-thickness defects \[4\]. This dressing can be used for two healing purposes, either for primary healing or as an intermediate in the preparation for a skin graft \[2\]. Compared to other biosynthetic dressings, porcine xenografts afford longer wound adherence and can be stored at room temperature \[1\]. The xenograft triggers rejection by the surgical defect, increasing local vascularization \[5\]. It also allows for rapid granulation, a reduced risk of infection, as well as reduced wound-related fluid and thermal losses \[6-8\]. There is also evidence that the quicker wound healing reduces the frequency of dressings, hospitalization time, pain, and analgesic \[9,10\]. Several clinical case series have extended the use of porcine xenografts to Mohs Micrographic Surgery (MMS) to facilitate post-operative wound care. Porcine xenograft dressings were determined to be safe, well-tolerated, and able to be applied to a wide anatomical range \[3,12\]. In addition to biosynthetic dressings, healing via second intention remains an alternative \[13,14\]. The extremities of elderly patients are a common location for wound granulation. Drawbacks to second intention healing on the extremities include prolonged healing time and extended wound care for the patient \[15\]. Chern et. al. completed a review of biological dressings in dermatologic surgery and concluded that there is a limited number of studies focusing on the conclusive benefits of dressings \[16\]. Although studies have established that EZ-DERM™ was helpful for wound healing following Mohs surgery, there have not been any definitive statistical measures reported in the literature. Additionally, there is a lack of studies assessing the direct comparison to second intention healing. Our plan is to perform a direct comparison of porcine xenograft placement to second intent healing. Based on the previously studied benefits of the xenograft as a barrier to the skin and one which has wound healing promoting factors, we believe that its use may result in decreased healing time, smaller scar size, better cosmetic outcomes, lower pain levels, and decreased rates of infection and other post-surgical complications. Our study will allow surgeons to make informed decisions on whether porcine xenograft dressing is superior to that of second intention healing and thus worth considering.
Interventions
DEVICEPorcine xenograft
The EZ-DERM™ porcine xenograft is a biosynthetic dressing made from porcine collagen containing aldehyde crosslinking. It has been most commonly applied to the management of 2nd degree burns, both partial-thickness and full-thickness defects. This dressing can be used for two healing purposes, either for primary healing or as an intermediate in the preparation for a skin graft
Sponsors
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The evaluator will not have knowledge of or access to the intervention that was performed and represents a provider not involved in the surgical care of the patient.
Intervention model description
To compare wound healing and scar quality following the placement of a porcine xenograft compared to second intention healing of leg wounds following Mohs or excisional surgery.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Over 18 years of age * Able to give informed consent themselves * Willing to return for follow-up visits * Post-operative defects greater than 8 mm (in greatest diameter or length of circular or oval geometric shape) on the lower extremities (including the feet) * Single defect
Exclusion criteria
* Mentally handicapped * Unable to understand written and oral English * Incarceration * Under 18 years of age * Unwilling to return for follow-up * Pregnant women * Wounds less than 8 mm in length * Wounds on the head, neck or digits * Patients in which primary linear closure is recommended
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient and Observer Scar Assessment Scale (POSAS) Observer Scale Total Score | Between 2.70 to 8.75 months | The primary outcome will be the total score of the POSAS observer scale, assessed at the 3-month (+/- 1 month) follow-up visit by two blinded evaluators who will not be involved in the placement of the porcine xenograft. For each patient, scores from the two blinded investigators will be combined by calculating the mean. The POSAS (Patient and Observer Scar Assessment Scale) is a validated assessment tool used for the assessment of all types of scars by professionals and patients. The observer scale is comprised of 6 items (vascularity, pigmentation, thickness, relief, pliability, and surface area) scored on a scale from 1(like normal skin) to 10 (worst scar imaginable). The total score is calculated as the sum of the six items (range, 6-60). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Healing Time | Up to 38 weeks | Healing time will be measured in weeks based on patient's responses to question 1 of the weekly follow-up questionnaire (Is the wound completely healed (i.e., wound is completely closed with no open areas)?). For example, a patient who first replies Yes to this question on the third weekly follow-up questionnaire will be assigned a healing time of 3 weeks. A more objective measure of healing time would not be feasible given our resources and patient schedule. |
| Ratio of Scar Size to Initial Defect Size | 3 months | The initial postoperative defect size will be measured by the investigator prior to intervention in terms of length and width using a sterile ruler. Initial defect area will be calculated as length times width. Scar size will be measured in terms of length and width at the 3-month follow-up visit, and scar area will be calculated as length times width. The outcome will be calculated by dividing the scar area by the initial defect area. |
| Pain Score at 1 Week Following Surgery | 1 week | Patients' pain scores will be measured based on their response to question 2 of the weekly follow-up questionnaire. Patients will be asked to rate their current pain level at the operative site on a scale from 1 (no pain) to 10 (worst imaginable pain). |
| POSAS Patient Scale Total Score | 3 months | Study participants will complete the POSAS patient scale at the 3-month follow-up visit. The POSAS (Patient and Observer Scar Assessment Scale) patient scale consists of 6 items assessing patients' subjective opinion of scar quality in terms of pain, itching, color, pliability, thickness, and relief. Each item is scored from 1 (normal pigmentation, no itching, etc.) to 10 (worst imaginable scar or sensation). The total score of the POSAS patient scale is calculated as the sum of the six items (range, 6-60). |
| Number of Participants With Infection | 3 months | Patient's charts will be reviewed at the completion of their 3-month office visit follow-up in order to analyze if they visited the dermatologist between the date of surgery and 3-month office visit and if infection was diagnosed. |
| Post-operative Bleeding Requiring Physician Intervention | 3 months | During each of the weekly follow-up questionnaires and during the 3-month follow-up visit, patients will be asked if they have experienced any post-operative bleeding that led to a visit to the physician (yes/no) and if there was any intervention performed by the physician to stop the bleeding (yes/no). The number and percentage of patients who experienced bleeding at any time during the 3-month follow-up period will be reported. |
| Pain Score of 6 or Higher at One Week | 1 week | The proportion of patients with a pain score greater than or equal to 6 at the operative site will be assessed at one week following surgery. This will be based on the patient's response to the weekly follow-up questionnaire, with scores ranging from 1 (no pain) to 10 (worst imaginable pain). |
| Number of Weeks With Pain Score Above 1 | 3 months | Patients' pain scores will be measured based on their response to question 2 of the weekly follow-up questionnaire. Patients will be asked to rate their current pain level at the operative site on a scale from 1 (no pain) to 10 (worst imaginable pain). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Porcine Xenograft Placement Porcine xenograft will be placed on the wound.
Porcine xenograft: The EZ-DERM™ porcine xenograft is a biosynthetic dressing made from porcine collagen containing aldehyde crosslinking. It has been most commonly applied to the management of 2nd degree burns, both partial-thickness and full-thickness defects. This dressing can be used for two healing purposes, either for primary healing or as an intermediate in the preparation for a skin graft | 8 |
| No Porcine Xenograft The wound will be allowed to heal via second intention. | 6 |
| Total | 14 |
Baseline characteristics
| Characteristic | No Porcine Xenograft | Total | Porcine Xenograft Placement |
|---|---|---|---|
| Age, Continuous | 80 years | 78 years | 75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 14 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Initial post-op defect size, area (length x width) | 6.0 centimeters squared | 5.7 centimeters squared | 5.7 centimeters squared |
| Medical history: current tobacco use | 0 Participants | 0 Participants | 0 Participants |
| Medical history: Diabetes | 1 Participants | 5 Participants | 4 Participants |
| Medical history: Skin infection | 1 Participants | 1 Participants | 0 Participants |
| Medical history: venous stasis | 4 Participants | 9 Participants | 5 Participants |
| Medication history: antibiotics | 1 Participants | 1 Participants | 0 Participants |
| Medication history: blood thinners | 4 Participants | 10 Participants | 6 Participants |
| Medication history: immunosuppressants | 1 Participants | 1 Participants | 0 Participants |
| Procedure type Excision | 1 Participants | 1 Participants | 0 Participants |
| Procedure type Mohs | 5 Participants | 13 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
| Surgical Site Ankle | 4 Participants | 6 Participants | 2 Participants |
| Surgical Site Calf | 2 Participants | 2 Participants | 0 Participants |
| Surgical Site Foot | 0 Participants | 2 Participants | 2 Participants |
| Surgical Site Shin | 0 Participants | 4 Participants | 4 Participants |
| Topical or systemic prophylaxis after surgery | 4 Participants | 10 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 4 / 8 | 3 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 |
Outcome results
Primary
Patient and Observer Scar Assessment Scale (POSAS) Observer Scale Total Score
The primary outcome will be the total score of the POSAS observer scale, assessed at the 3-month (+/- 1 month) follow-up visit by two blinded evaluators who will not be involved in the placement of the porcine xenograft. For each patient, scores from the two blinded investigators will be combined by calculating the mean. The POSAS (Patient and Observer Scar Assessment Scale) is a validated assessment tool used for the assessment of all types of scars by professionals and patients. The observer scale is comprised of 6 items (vascularity, pigmentation, thickness, relief, pliability, and surface area) scored on a scale from 1(like normal skin) to 10 (worst scar imaginable). The total score is calculated as the sum of the six items (range, 6-60).
Time frame: Between 2.70 to 8.75 months
Population: The Modified Intention-to-Treat (mITT) Population consisted of all patients who received the study intervention and completed the 3-month office visit follow-up, during which the primary endpoint was evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Porcine Xenograft Placement | Patient and Observer Scar Assessment Scale (POSAS) Observer Scale Total Score | 17.0 score on a scale |
| No Porcine Xenograft | Patient and Observer Scar Assessment Scale (POSAS) Observer Scale Total Score | 20.5 score on a scale |
p-value: 0.0495% CI: [-8, -0.5]Wilcoxon (Mann-Whitney)
Secondary
Healing Time
Healing time will be measured in weeks based on patient's responses to question 1 of the weekly follow-up questionnaire (Is the wound completely healed (i.e., wound is completely closed with no open areas)?). For example, a patient who first replies Yes to this question on the third weekly follow-up questionnaire will be assigned a healing time of 3 weeks. A more objective measure of healing time would not be feasible given our resources and patient schedule.
Time frame: Up to 38 weeks
Population: The Modified Intention-to-Treat (mITT) Population consisted of all patients who received the study intervention and completed the 3-month office visit follow-up, during which the primary endpoint was evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Porcine Xenograft Placement | Healing Time | 14.0 weeks |
| No Porcine Xenograft | Healing Time | 13.0 weeks |
p-value: 195% CI: [-19, 20]Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Infection
Patient's charts will be reviewed at the completion of their 3-month office visit follow-up in order to analyze if they visited the dermatologist between the date of surgery and 3-month office visit and if infection was diagnosed.
Time frame: 3 months
Population: The analysis population for this endpoint was the Safety Population, which consisted of all patients who receive the randomized study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Porcine Xenograft Placement | Number of Participants With Infection | 2 Participants |
| No Porcine Xenograft | Number of Participants With Infection | 2 Participants |
p-value: 195% CI: [0.03, 13.3]Fisher Exact
Secondary
Number of Weeks With Pain Score Above 1
Patients' pain scores will be measured based on their response to question 2 of the weekly follow-up questionnaire. Patients will be asked to rate their current pain level at the operative site on a scale from 1 (no pain) to 10 (worst imaginable pain).
Time frame: 3 months
Population: The Modified Intention-to-Treat (mITT) Population consisted of all patients who received the study intervention and completed the 3-month office visit follow-up, during which the primary endpoint was evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Porcine Xenograft Placement | Number of Weeks With Pain Score Above 1 | 2.0 weeks |
| No Porcine Xenograft | Number of Weeks With Pain Score Above 1 | 1.0 weeks |
p-value: 0.5495% CI: [-1, 2]Wilcoxon (Mann-Whitney)
Secondary
Pain Score at 1 Week Following Surgery
Patients' pain scores will be measured based on their response to question 2 of the weekly follow-up questionnaire. Patients will be asked to rate their current pain level at the operative site on a scale from 1 (no pain) to 10 (worst imaginable pain).
Time frame: 1 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Porcine Xenograft Placement | Pain Score at 1 Week Following Surgery | 1.0 score on a scale |
| No Porcine Xenograft | Pain Score at 1 Week Following Surgery | 1.5 score on a scale |
p-value: 195% CI: [-6, 4]Wilcoxon (Mann-Whitney)
Secondary
Pain Score of 6 or Higher at One Week
The proportion of patients with a pain score greater than or equal to 6 at the operative site will be assessed at one week following surgery. This will be based on the patient's response to the weekly follow-up questionnaire, with scores ranging from 1 (no pain) to 10 (worst imaginable pain).
Time frame: 1 week
Population: The analysis population for this endpoint was all subjects in the Safety Population with a non-missing pain score at week 1. The safety Population consisted of all patients who received the randomized study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Porcine Xenograft Placement | Pain Score of 6 or Higher at One Week | 1 Participants |
| No Porcine Xenograft | Pain Score of 6 or Higher at One Week | 1 Participants |
p-value: 195% CI: [0.006, 55.9]Fisher Exact
Secondary
POSAS Patient Scale Total Score
Study participants will complete the POSAS patient scale at the 3-month follow-up visit. The POSAS (Patient and Observer Scar Assessment Scale) patient scale consists of 6 items assessing patients' subjective opinion of scar quality in terms of pain, itching, color, pliability, thickness, and relief. Each item is scored from 1 (normal pigmentation, no itching, etc.) to 10 (worst imaginable scar or sensation). The total score of the POSAS patient scale is calculated as the sum of the six items (range, 6-60).
Time frame: 3 months
Population: The Modified Intention-to-Treat (mITT) Population consisted of all patients who received the study intervention and completed the 3-month office visit follow-up, during which the primary endpoint was evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Porcine Xenograft Placement | POSAS Patient Scale Total Score | 15.0 score on a scale |
| No Porcine Xenograft | POSAS Patient Scale Total Score | 18.0 score on a scale |
p-value: 0.7595% CI: [-9, 12]Wilcoxon (Mann-Whitney)
Secondary
Post-operative Bleeding Requiring Physician Intervention
During each of the weekly follow-up questionnaires and during the 3-month follow-up visit, patients will be asked if they have experienced any post-operative bleeding that led to a visit to the physician (yes/no) and if there was any intervention performed by the physician to stop the bleeding (yes/no). The number and percentage of patients who experienced bleeding at any time during the 3-month follow-up period will be reported.
Time frame: 3 months
Population: The analysis population for this outcome was the Safety Population, consisting of all patients who received the randomized study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Porcine Xenograft Placement | Post-operative Bleeding Requiring Physician Intervention | 0 Participants |
| No Porcine Xenograft | Post-operative Bleeding Requiring Physician Intervention | 1 Participants |
p-value: 0.4395% CI: [-0.564, 0.185]Fisher Exact
Secondary
Ratio of Scar Size to Initial Defect Size
The initial postoperative defect size will be measured by the investigator prior to intervention in terms of length and width using a sterile ruler. Initial defect area will be calculated as length times width. Scar size will be measured in terms of length and width at the 3-month follow-up visit, and scar area will be calculated as length times width. The outcome will be calculated by dividing the scar area by the initial defect area.
Time frame: 3 months
Population: The Modified Intention-to-Treat (mITT) Population consisted of all patients who received the study intervention and completed the 3-month office visit follow-up, during which the primary endpoint was evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Porcine Xenograft Placement | Ratio of Scar Size to Initial Defect Size | 0.43 ratio |
| No Porcine Xenograft | Ratio of Scar Size to Initial Defect Size | 0.35 ratio |
p-value: 195% CI: [-0.26, 0.33]Wilcoxon (Mann-Whitney)
Post Hoc
Number of Patients Receiving Rescue Medication
This outcome describes the number of patients in each treatment group receiving treatment with silver nitrate sticks as a rescue medication due to lack of complete wound healing at the 3-month (+- 1 month) visit following surgery.
Time frame: 3 months
Population: The Modified Intention-to-Treat (mITT) Population consisted of all patients who received the study intervention and completed the 3-month office visit follow-up, during which the primary endpoint was evaluated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Porcine Xenograft Placement | Number of Patients Receiving Rescue Medication | 2 Participants |
| No Porcine Xenograft | Number of Patients Receiving Rescue Medication | 1 Participants |