A Randomized, Double-Blinded, Controlled Trial Evaluating Recombinant Human Platelet-Derived Growth Factor B (rhPDGF-BB)-Enhanced Wound Matrix in the Reconstruction of Full-Thickness Head or Neck Defects Following Skin Cancer Excision
概览
- 阶段
- 2 期
- 干预措施
- Saline
- 疾病 / 适应症
- Wound Healing
- 发起方
- Vanderbilt University Medical Center
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Time-to-Readiness for Skin Graft in Days
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
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.
研究者
Wesley Thayer
Vice Chair of Research, Department of Plastic Surgery
Vanderbilt University Medical Center
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Saline matrix
Participants receive wound matrix saturated with normal saline.
干预措施: Saline
rhPDGF-BB matrix
Participants receive wound matrix saturated with rhPDGF-BB.
干预措施: RhPDGF-BB
结局指标
主要结局
Time-to-Readiness for Skin Graft in Days
时间窗: 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
次要结局
- Granulation Rate(Daily, starting at day 7 up to day 56 following the baseline procedure)
- Aesthetics Rating at Week 8(Week 8)
- Change from Baseline in Pain on an 11-Point Scale(From enrollment through week 8)
- Change from Baseline in Quality of Life(From enrollment through week 8)
- Number of Participants Recruited and Eligible(Monthly up to month 15)
- Number of Participants Randomized Per Month(Monthly up to month 15)
- Proportion of Participants Retained at Week 8(Week 8)
- Weekly Percentage of Completed Daily Photos at Week 8(Weekly, week 1 up to week 8)
- Change in Granulation on a 5-Point Scale(Weekly, starting at week 1 up to week 8 following the baseline procedure)
- Scar Scale at Week 8(Week 8)
- Time to re-epithelialization(Daily, starting at day 7 up to day 56 following the baseline procedure)
- Re-epithelialization rate(Daily, starting at day 7 up to day 56 following the baseline procedure)
- Time to complete healing(Daily, starting at day 7 up to day 56 following the baseline procedure)
- Healing rate(Daily, starting at day 7 up to day 56 following the baseline procedure)