Surgical Wound, Wound Healing
Conditions
Keywords
Complex Surgical Defect, Skin Cancer Excision, Platelet-Derived Growth Factor
Brief summary
Skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma lesions that develop on the head and neck are treated by Mohs surgery or wide local excision to remove all tumor cells and preserve the normal tissue. These surgical techniques may result in large defects requiring reconstruction to restore function and aesthetics. Rotational flaps and free flaps are techniques used to reconstruct large, complex defects that cannot be closed with sutures, staples, or glue. Older, frail patients are particularly vulnerable to complications from these procedures often leaving them to care for chronic wounds until a skin graft can be placed. Phenome-wide association studies (PheWAS) revealed a cohort of patients with a single nucleotide variant (SNV) in PDGFRβ having a higher incidence of chronic skin ulcers, skin grafts, and other skin and connective tissue disorders suggesting that the loss of PDGFβ signaling may impair healing following trauma. rhPDGF-BB, a recombinant human platelet derived growth factor protein-based therapy, signals through PDGFRβ to mediate inflammation, granulation, angiogenesis, and remodeling during wound healing and skin repair and is FDA cleared for diabetic neuropathic ulcers and periodontal bone and soft tissue reconstructions. These data suggest rhPDGF-BB may be a viable therapeutic strategy to augment the reconstruction of these complex defects by accelerating granulation, epithelialization, and wound closure.
Detailed description
This Phase II clinical trial will evaluate the potential efficacy of rhPDGF-BB-enhanced wound matrix versus wound matrix saturated with normal saline to augment healing of head and neck defects that cannot be healed by primary intention following skin cancer excision. This prospective, double-blinded, single-site study will randomize participants into two arms - intervention and control - comparing the granulation, re-epithelialization, complete healing, and scarring of the wound bed, pain, and quality of life. After recruiting, consenting, and screening, participants will undergo the baseline procedure to place the wound matrix into the wound bed. Randomization will occur immediately before the baseline procedure, and both the PI and participant will be blinded. To achieve balance in treatment allocation, randomization blocks of 4 (2 interventions : 2 controls) will be stratified by anatomical location, scalp versus face/neck, and greatest dimension, \< 3cm versus \> 3cm, of the surgical defect. Following the baseline procedure, participants will return for their first follow-up visit on day 6 for a clinical examination, suture removal, and wound dressing change, and then again at weeks 4 and 8 for a clinical exam and photographs. Pain and adverse events will be evaluated and documented weekly through the participants' electronic health records, phone call, email survey, or in-person. Participants will submit daily photographs of the wound while performing dressing changes at home starting on day 7 until day 56. These photographs will be taken using a wound imaging application that will be downloaded to a personal mobile device with assistance from the study coordinator. Each patient will also receive a hard copy of instructions for using the application at home. The mobile application can ensure quality photographs and transfer the images to a password-protected cloud-based portal. The photographs will be analyzed by blinded wound experts, retrospectively, to determine the precise day that the wound bed achieved 81-100% granulation. The imaging software will also be used to trace and measure the rate of healing by granulation, re-epithelialization, and wound closure. Under routine care with a wound matrix (no rhPDGF-BB), the average time to granulation is 4-6 weeks in this patient population. Here, we aim to reduce the time to readiness by adding rhPDGF-BB. It is expected that all participants will complete the study which begins at time of signing informed consent and ends at the final study follow-up visit.
Interventions
DRUGRhPDGF-BB
0.3 mg/mL rhPDGF-BB
DRUGSaline
Normal saline
Sponsors
Lynch Regenerative Medicine
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Underwent surgery to completely remove skin cancer, either Mohs micrographic or wide local excision, that left a full-thickness surgical defect of the head or neck measuring between 1.5-10cm in greatest dimension with clear margins as assessed in the pathology report. * Margins of the wound cannot be approximated or closed with stitches, sutures, staples, or glue * Surgeon does not plan for immediate skin graft or flap * Aged \>21 years old * Willing and able to provide informed consent for study participation and compliance with study protocol * Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion criteria
* Medical conditions that would, in the opinion of the Investigator or treating provider, compromise the safety of the individual with study participation and/or the ability of the individual to follow study protocol * The device will not fit the contour of the base of the wound bed * Evidence of current clinical infection as demonstrated by the invasion of bacteria into the healthy viable tissue on the periphery of the wound (colonization of wound bed due to normal flora or environment is not exclusionary) * Prior radiation therapy at the application site * Known allergic reactions to porcine tissue, porcine collagen, or yeast-derived products * Currently enrolled in a drug or device trial or within 30 days of last investigational drug or device administration at baseline visit where investigational treatment (drug or device) was placed in wound bed or may potentially interact with study treatment * Women who are pregnant, breastfeeding, or planning to become pregnant during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-Readiness for Skin Graft in Days | Daily, starting at day 7 up to day 56 following the baseline procedure | Time to 81-100% granulation of wounds as assessed by expert clinical review of photographs taken daily starting at day 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Granulation Rate | Daily, starting at day 7 up to day 56 following the baseline procedure | Percent granulation versus time in days as determined by clinical assessment of the percent granulation of the wound bed in photographic images taken daily starting at day 7 following the baseline procedure. |
| Change in Granulation on a 5-Point Scale | Weekly, starting at week 1 up to week 8 following the baseline procedure | Weekly ordinal scale outcomes of granulation as determined by clinical review of wound bed granulation in photographs taken daily starting at day 7 following the baseline procedure. Ordinal scale ranges from 1 to 5 in the increments below. * 0-20% granulation = 1 * 21-40% granulation = 2 * 41-60% granulation = 3 * 61-80% granulation = 4 * 81-100% = 5 |
| Time to re-epithelialization | Daily, starting at day 7 up to day 56 following the baseline procedure | Time to 100% re-epithelialization as assessed by expert clinicians utilizing the NetHealth Tissue Analytics software to measure the percent of new epithelial tissue formed on the wound in daily photographs |
| Re-epithelialization rate | Daily, starting at day 7 up to day 56 following the baseline procedure | Percent re-epithelialization versus time as assessed by expert clinicians utilizing the NetHealth Tissue Analytics software to measure the percent of new epithelial tissue formed on the wound in daily photographs |
| Time to complete healing | Daily, starting at day 7 up to day 56 following the baseline procedure | Time to complete healing as assessed by expert clinicians utilizing the NetHealth Tissue Analytics software to measure wound closure in daily photographs |
| Healing rate | Daily, starting at day 7 up to day 56 following the baseline procedure | Wound size change over time to as assessed by expert clinicians utilizing the NetHealth Tissue Analytics software to measure wound closure in daily photographs |
| Aesthetics Rating at Week 8 | Week 8 | Aesthetics rating of the wound as assessed by clinical examination at the final week 8 follow-up visit using an ordinal scale from 0 (very ugly) to 10 (very nice). |
| Scar Scale at Week 8 | Week 8 | Scar rating of the wound as assessed by clinical examination at the final week 8 follow-up visit, with rating determined by the score on the Manchester Scar Scale. This score is calculated from four ordinal scales that range from 1-4, with 1 indicating a better scar and 4 indicating a worse scar. |
| Change from Baseline in Pain on an 11-Point Scale | From enrollment through week 8 | Weekly self-reported participant surveys will assess average pain intensity on an 11-point scale. Possible scores range from 0 (No Pain) to 10 (Worst Pain). |
| Change from Baseline in Quality of Life | From enrollment through week 8 | Change in quality of life based on a self-reported 12-question survey taken at baseline and at week 8. |
| Number of Participants Recruited and Eligible | Monthly up to month 15 | Total number of participants that were recruited and eligible for the study. |
| Number of Participants Randomized Per Month | Monthly up to month 15 | Number of participants that were randomized each month of the study. |
| Proportion of Participants Retained at Week 8 | Week 8 | Proportion of participants retained in the study at week 8 (end of study). |
| Weekly Percentage of Completed Daily Photos at Week 8 | Weekly, week 1 up to week 8 | Participant adherence to daily wound photograph schedule. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWesley Self
Vanderbilt University Medical Center
Outcome results
None listed