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

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

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.

Study Overview

• Status: Completed
• Conditions: Wound Heal
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APIS Biomaterial on the Head; 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.; 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.
Experimental: APIS Biomaterial on the Lower Extremities; 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.; 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.
Active Comparator: Standard Secondary Intention Healing on the Head; 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; 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.
Active Comparator: Standard Secondary Intention Healing on the Lower Extremities; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Study Director: Anna S Clayton, MD, Vanderbilt University Medical Center Dermatology

Publications and helpful links

General Publications

• Yang YW, Ochoa SA. Use of Porcine Xenografts in Dermatology Surgery: The Mayo Clinic Experience. Dermatol Surg. 2016 Aug;42(8):985-91. doi: 10.1097/DSS.0000000000000804.
• Zitelli JA. Wound healing by secondary intention. A cosmetic appraisal. J Am Acad Dermatol. 1983 Sep;9(3):407-15. doi: 10.1016/s0190-9622(83)70150-7.
• Chern PL, Baum CL, Arpey CJ. Biologic dressings: current applications and limitations in dermatologic surgery. Dermatol Surg. 2009 Jun;35(6):891-906. doi: 10.1111/j.1524-4725.2009.01153.x. Epub 2009 Apr 6.
• Zitelli JA. Secondary intention healing: an alternative to surgical repair. Clin Dermatol. 1984 Jul-Sep;2(3):92-106. doi: 10.1016/0738-081x(84)90031-2. No abstract available.
• Donaldson MR, Coldiron BM. Scars after second intention healing. Facial Plast Surg. 2012 Oct;28(5):497-503. doi: 10.1055/s-0032-1325643. Epub 2012 Oct 1.
• Stebbins WG, Gusev J, Higgins HW 2nd, Nelson A, Govindarajulu U, Neel V. Evaluation of patient satisfaction with second intention healing versus primary surgical closure. J Am Acad Dermatol. 2015 Nov;73(5):865-7.e1. doi: 10.1016/j.jaad.2015.07.019. No abstract available.
• Eaglstein WH, Iriondo M, Laszlo K. A composite skin substitute (graftskin) for surgical wounds. A clinical experience. Dermatol Surg. 1995 Oct;21(10):839-43. doi: 10.1111/j.1524-4725.1995.tb00709.x.
• Mott KJ, Clark DP, Stelljes LS. Regional variation in wound contraction of mohs surgery defects allowed to heal by second intention. Dermatol Surg. 2003 Jul;29(7):712-22. doi: 10.1046/j.1524-4725.2003.29180.x.
• Deutsch BD, Becker FF. Secondary healing of Mohs defects of the forehead, temple, and lower eyelid. Arch Otolaryngol Head Neck Surg. 1997 May;123(5):529-34. doi: 10.1001/archotol.1997.01900050085011.
• Chetter IC, Oswald AV, McGinnis E, Stubbs N, Arundel C, Buckley H, Bell K, Dumville JC, Cullum NA, Soares MO, Saramago P. Patients with surgical wounds healing by secondary intention: A prospective, cohort study. Int J Nurs Stud. 2019 Jan;89:62-71. doi: 10.1016/j.ijnurstu.2018.09.011. Epub 2018 Sep 18.
• McMurray SL, Wallace MM, Stebbins WG, Clayton AS. Use of a Novel Biomaterial to Enhance Secondary Intention Healing. Dermatol Surg. 2021 Jun 1;47(6):843-844. doi: 10.1097/DSS.0000000000002725. No abstract available.
• Dixon AJ, Dixon MP, Askew DA, Wilkinson D. Prospective study of wound infections in dermatologic surgery in the absence of prophylactic antibiotics. Dermatol Surg. 2006 Jun;32(6):819-26; discussion 826-7. doi: 10.1111/j.1524-4725.2006.32167.x.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2020
• Primary Completion (Actual): March 8, 2022
• Study Completion (Actual): March 8, 2022

Study Registration Dates

• First Submitted: September 3, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (Actual): September 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Mohs surgery; Manuka honey; Secondary intention wound healing
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 201414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes