Enhanced Secondary Intention Healing vs. Standard Secondary Intention Healing in Mohs Surgical Defects on the Head and Distal Lower Extremities

Study Overview
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Brief Summary
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The purpose of this study is to elucidate if a novel biomaterial containing gelatin, manuka honey, and hydroxyapatite enhances secondary intention healing when compared to conventional secondary intention healing for surgical defects after Mohs micrographic surgery on the head and distal lower extremities (below the knee). This novel biomaterial has already been FDA cleared for surgical wounds.

Detailed Description
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Secondary intention healing (SIH) is often underutilized and has several advantages compared to primary surgical repair. Wound care is minimal, bleeding and infection are rare, and risks associated with primary closure (e.g. hematoma, suture granuloma, graft or flap failure) are non-existent. Importantly, SIH facilitates surveillance of tumor recurrence, whereas flaps and grafts may bury residual tumor. When used in appropriate anatomical locations, SIH leads to high patient satisfaction. However, SIH requires regular wound care that can be cumbersome to patients. Prior studies utilizing biologic dressings have shown patients report better quality of life during the post-operative period related to less pain, decreased dressing changes, and faster healing times. Biologic dressings provide an alternative to surgical autografts and eliminate the risks associated with graft harvesting (e.g. pain, infection, and scarring). For many patients, the cosmetic outcome following healing is important. However, cosmetic outcome with SIH is variable and depends on many factors, namely location (e.g. concavities favorable), skin laxity, and underlying musculature. Exuberant granulation tissue, hypopigmented and telangiectatic scars are the most frequent adverse cosmetic outcomes with SIH. The novel biomaterial APIS® (SweetBio, Inc. Memphis, TN) is an advanced synthesis of gelatin, manuka honey, and hydroxyapatite bioengineered to protect wounds, manage exudate, and maintain a moist environment. It is FDA cleared (FDA number K1827250) for wound management across 9 indications including surgical wounds. It has been used successfully in a small case series of 8 patients for post-operative Mohs surgical wounds on the head and distal lower extremities. Time to complete re-epithelialization was 6 weeks (42 days), suggesting a reduction in healing time compared to standard SIH times for the leg and head of 127 and 57 days, respectively. Use of this novel biomaterial to enhance SIH is hypothesized to reduce healing times when compared to standard SIH wound care. This provides a useful option to aid SIH in sites like the lower legs, where healing can be prolonged due to intrinsic factors (e.g., cardiovascular disease, peripheral vascular disease, diabetes) or extrinsic factors (e.g., increased risk of surgical site infection following dermatologic surgery at sites below the knee). Randomized, comparative studies evaluating augmented SIH compared to conventional SIH in dermatologic surgery are limited. This study aims to evaluate whether use of a novel biomaterial enhances SIH, particularly in shortening time to complete re-epithelialization. Patients undergoing Mohs micrographic surgery amenable to SIH on the head and distal lower extremities will be randomized into one of four groups (standard SIH or biomaterial APIS® enhanced SIH on the head or distal lower extremities). Patients will have regularly scheduled follow-up with questionnaires at each visit. The investigators aim to evaluate whether use of this novel biomaterial decreases complete re-epithelialization times, reduces infection rates, and improves cosmetic outcomes.

Official Title
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Novel Biomaterial Containing Gelatin, Manuka Honey, and Hydroxyapatite Enhanced Secondary Intention Healing vs. Standard Secondary Intention Healing in Mohs Surgical Defects on the Head and Distal Lower Extremities - A Randomized Clinical Trial

Conditions
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Wound Heal

Intervention / Treatment
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* Device: Participants in this group will receive the experimental APIS Biomaterial on the Head.
* Device: Participants in this group will receive the experimental APIS Biomaterial on the Lower Extremities.
* Other: Standard Secondary Intention Healing on the Head
* Other: Standard Secondary Intention Healing on the Lower Extremities


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Post-operative wounds following Mohs surgery on the head or distal lower extremities Single Mohs post-operative defect Post-operative wounds greater than 1cm in width Depth of defect at least to subcutaneous tissue Patients have the ability to provide their own wound care Agreeable to regularly scheduled follow-up visits and transmission of photos via HIPAA compliant Vanderbilt University Medical Center Box Patients are able to provide informed consent Exclusion Criteria: Under 18 years of age Unable to provide informed consent Unable to understand oral and written English Post-operative wounds not appropriate for secondary intention healing Sensitivity or allergy to APIS® biomaterial including collagen and its derivatives, porcine-derived materials or honey Immunosuppressed and organ transplant patients Post-operative wounds superficial to subcutaneous tissue

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APIS Biomaterial on the Head<br>Participants in this group will receive the experimental APIS Biomaterial on the Head. One layer of APIS® will be applied to the post-operative wound covered by petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape. The biomaterial will be reapplied if it is completely absorbed at follow up and the wound depth below the epithelial level. | Device: Participants in this group will receive the experimental APIS Biomaterial on the Head.<br>* One layer of APIS® will be applied to the post-operative wound on the head covered by petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape.<br>|
| Experimental: APIS Biomaterial on the Lower Extremities<br>Participants in this group will receive the experimental APIS Biomaterial on the Lower Extremities. One layer of APIS® will be applied to the post-operative wound covered by petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape. The biomaterial will be reapplied if it is completely absorbed at follow up and the wound depth below the epithelial level. | Device: Participants in this group will receive the experimental APIS Biomaterial on the Lower Extremities.<br>* One layer of APIS® will be applied to the post-operative wound on the lower extremities covered by petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape.<br>|
| Active Comparator: Standard Secondary Intention Healing on the Head<br>Participants in this group will receive standard secondary intention wound healing post-operative care on the Head. Post-operative wound will heal via conventional secondary intention. Application of petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape. | Other: Standard Secondary Intention Healing on the Head<br>* Participants in this group will receive standard secondary intention wound healing post-operative care on the Head. Post-operative wound will heal via conventional secondary intention. Application of petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape.<br>|
| Active Comparator: Standard Secondary Intention Healing on the Lower Extremities<br>Participants in this group will receive standard secondary intention wound healing post-operative care on the Lower Extremities. Post-operative wound will heal via conventional secondary intention. Application of petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape. | Other: Standard Secondary Intention Healing on the Lower Extremities<br>* Participants in this group will receive standard secondary intention wound healing post-operative care on the Lower Extremities. Post-operative wound will heal via conventional secondary intention. Application of petrolatum impregnated gauze, a non-stick Telfa pad, gauze, and Opsite tape.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Complete Wound Re-epithelialization on the Head | Complete wound re-epithelialization is defined by epidermal regrowth covering entire post-operative defect. Patients will be seen in office 14 days post-operative, then every 14 days thereafter until complete re-epithelialization is achieved. Patients will also submit photos via Vanderbilt HIPAA compliant Box at regular follow-up intervals (post-operative day 7 then every 14 days thereafter until complete re-epithelialization is achieved). Time elapsed from surgery date to complete re-epithelialization will be noted in days. Time will be measured in days. Increased days indicates slower wound healing. | 14 days post-operative until complete re-epithelialization, approximately 5 months | 
| Time to Complete Wound Re-epithelialization on the Lower Extremities | Complete wound re-epithelialization is defined by epidermal regrowth covering entire post-operative defect. Patients will be seen in office 14 days post-operative, then every 14 days thereafter until complete re-epithelialization is achieved. Patients will also submit photos via Vanderbilt HIPAA compliant Box at regular follow-up intervals (post-operative day 7 then every 14 days thereafter until complete re-epithelialization is achieved). Time elapsed from surgery date to complete re-epithelialization will be noted in days. Time will be measured in days. Increased days indicates slower wound healing. | 14 days post-operative until complete re-epithelialization, approximately 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Self Reported Pain Score | Patients self-reported their surgical site/wound pain during each 2-week follow-up visit via a questionnaire. Scores were collected from participants until complete wound re-epithelialization, which was approximately 5 months for each participant. Pain scale will range from 1 (no pain) to 10 (worst pain imaginable). These pain scores were then averaged amongst the participants included in each arm. | Baseline to complete wound re-epithelialization, approximately 5 months | 
| Number of Participants With at Least One Post-Operative Wound Infection | Post-operative wounds will be assessed for infection at regularly scheduled follow-ups. Any clinically suspected infection (e.g. erythema, purulence, malodor) will be reported. | Baseline to complete re-epithelialization, approximately 5 months | 
| Number of Participants With at Least One Report of Post-operative Bleeding | Patients will report any bleeding (yes/no) via questionnaires at regularly scheduled follow-up appointments. | Baseline to complete re-epithelialization, approximately 5 months | 
| Skin Thickness | Participants were given a questionnaire at the final visit when complete wound re-epithelialization had been achieved (which was approximately 5 months for each participant) and asked, Is the thickness of the scar different from your normal skin at present? Participants reported on a scale of 1 (no, as normal skin) to 10 (yes, very different). These skin thickness scores were then averaged amongst the participants included in each arm. | Baseline to complete wound re-epithelialization, approximately 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mohs surgery, Manuka honey, Secondary intention wound healing