Use of Autologous Platelet-Rich Plasma to Treat Hypertrophic Burn Scars

Use of Autologous Platelet-Rich Plasma to Treat Hypertrophic Burn Scars; A Randomized Controlled Double-Blinded Trial

Hypertrophic burn scars are experienced by more than 70% of burn victims. They are a major source of decreased quality of life in burn patients due to pain, decreased range of motion, and poor cosmetic appearance. Current treatment strategies (including fat grafting and laser resurfacing) are either highly invasive, prohibitively costly, or painful. Autologous Platelet Rich Plasma (PRP) does not require anesthesia, and is an inexpensive, safe, fast, and less painful alternative that has been recognized for its role in reducing scars associated with acne, among other things. While PRP has not been studied specifically in burn scars, there is sufficient theoretical and practical evidence that it will improve the appearance and feel of these debilitating scars, representing a large potential benefit for these patients with minimal associated risk.

Study Overview

• Status: Terminated
• Conditions: Hypertrophic Scar
• Intervention / Treatment: Biological: PRP Injection; Drug: Saline Injection

Detailed Description

Severe burn injury is associated with hypertrophic scarring, which occurs in up to 70% of burn patients (Finnerty et al., 2016). Burn scars are particularly troublesome because they cause debilitating neuropathic pain and itch, joint contractures and stiffness that limit range of motion, inability to sweat, and physical disfigurement of cosmetically sensitive areas such as the hands and face.

Autologous platelet-rich plasma (PRP) is plasma with a higher concentration of platelets, and is prepared by drawing up a small amount of a patient's blood, centrifuging it, and collecting the platelet-rich layer. Many automated machines exist for doing this process. Platelets contain a multitude of growth factors and other small molecules that have been shown to promote wound healing and tissue regeneration in a variety of contexts. PRP, which is rich in these healing growth factors, has been studied extensively and has proved to be both a safe and effective treatment modality for a wide range of applications, including acne scars and hair loss (Elghblawi et al., 2018). It has been shown to be a safe and effective treatment for some types of surgical and traumatic scars, and has been safely applied to acute burn wounds where it has been shown to improve healing and subsequent scarring (Venter et al., 2016). Despite these known uses of PRP, its role in reducing the extent and severity of mature hypertrophic burn scars after they have already healed is notably lacking in the literature.

The purpose of this study is to assess whether intradermally-injected autologous platelet-rich plasma improves the size, texture, color, elasticity, contour, and neuropathic pain associated with mature burn scars.

Specific Aims:

1. Compare the effectiveness of intradermally-injected autologous platelet-rich plasma versus normal saline (NS) to improve burn scars, as measured by both clinician-reported (Vancouver scar scale; VSS) and patient-reported measures (Patient and Observer Scar Assessment Scale; POSAS).
2. Compare the effectiveness of intradermally-injected autologous platelet-rich plasma versus normal saline as a control to improve neuropathic pain associated with burn scars.
3. Understand the mechanism of action of PRP in improving burn scars via histological analysis of collagen content in the burn scar tissue biopsy specimens.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

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 to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hypertrophic burn scar present on trunk or abdomen

Exclusion Criteria:

• Initial burn injury less than 1 year old
• History of chemical or electrical burn
• Genetic or acquired conditions that severely affect systemic wound healing or collagen formation (vasculitis, diabetes, Ehlers-Danlos syndrome, radiation therapy to the scar site or use of immunosuppressive medications within the last year, active cancer)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRP injection right half; The scar to be treated will first be wiped with an alcohol swab, then measured and marked out with a marking pen such that the entirety of the scar will fit into a symmetric ellipse that is drawn, and the ellipse is filled entirely with the scar tissue. A ruler will be used to measure the scar in its greatest horizontal span, and the midway point will be marked with a vertical line. A coin flip will determine if the PRP injection (the experimental half) will be on the right half of the scar (as opposed to the left half). The half of the scar that will not receive PRP will be the control half. After finishing the VSS and POSAS, the area inside the control half of the ellipse will then be subdivided with a marking pen into 1cm x 1cm square boxes, with the plan of injecting 1mL normal saline into each 1 square cm box at 0 months, 1 month, 4 months, and 6 months. Punch biopsies from each scar will be will be obtained at both six months and one year from enrollment.	Biological: PRP Injection; 1mL platelet rich plasma will be injected into each 1cm x 1cm area of scar tissue of the experimental half of the scar.; Drug: Saline Injection; 1mL NS will be injected into each 1cm x 1cm area of scar tissue of the control half of the scar.
Experimental: PRP injection left half; The scar to be treated will first be wiped with an alcohol swab, then measured and marked out with a marking pen such that the entirety of the scar will fit into a symmetric ellipse that is drawn, and the ellipse is filled entirely with the scar tissue. A ruler will be used to measure the scar in its greatest horizontal span, and the midway point will be marked with a vertical line. A coin flip will determine if the PRP injection (the experimental half) will be on the right half of the scar (as opposed to the left half). The half of the scar that will not receive PRP will be the control half. After finishing the VSS and POSAS, the area inside the experimental half of the ellipse will then be subdivided with a marking pen into 1cm x 1cm square boxes, with the plan of injecting 1mL PRP into each 1 square cm box at 0 months, 1 month, 4 months, and 6 months. Punch biopsies from each scar will be will be obtained at both six months and one year from enrollment.	Biological: PRP Injection; 1mL platelet rich plasma will be injected into each 1cm x 1cm area of scar tissue of the experimental half of the scar.; Drug: Saline Injection; 1mL NS will be injected into each 1cm x 1cm area of scar tissue of the control half of the scar.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scar Assessment: POSAS at 2 Months	Scar will be measured by Patient and Observer Scar Assessment Scale ( POSAS ) on both sides of the scar. POSAS score is an assessment of scar severity. The range is 6-60. 6=normal skin and 60= severely scarred skin.	2 months
Scar Assessment: VSS at 2 Months	Scar will be measured by Vancouver Scar Scale (VSS) on both control half and experimental half. VSS score is an assessment of scar severity. Four characteristics of the scar are assessed. These are: vascularity, height, pliability, and pigmentation. Each characteristic is given a score, which are added together to give an overall score between 0 and 13. 0= normal; 13=severely scarred.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Scar assessment: POSAS 1 year	Scar will be measured by Patient and Observer Scar Assessment Scale ( POSAS ) on both sides of the scar. POSAS score is an assessment of scar severity. The range is 6-60. 6=normal skin and 60= severely scarred skin.	Baseline to 1 year
Change in Scar Assessment: VSS 1 year	Scar will be measured by Vancouver Scar Scale (VSS) on both control half and experimental half. VSS score is an assessment of scar severity. The scale range is 14-140. 14=normal skin and 140= severely scarred skin.	Baseline to 1 year

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Galen Perdikis, MD, Vanderbilt University School of Medicine

Publications and helpful links

General Publications

• Cervelli V, Nicoli F, Spallone D, Verardi S, Sorge R, Nicoli M, Balzani A. Treatment of traumatic scars using fat grafts mixed with platelet-rich plasma, and resurfacing of skin with the 1540 nm nonablative laser. Clin Exp Dermatol. 2012 Jan;37(1):55-61. doi: 10.1111/j.1365-2230.2011.04199.x.
• Prochazka V, Klosova H, Stetinsky J, Gumulec J, Vitkova K, Salounova D, Dvorackova J, Bielnikova H, Klement P, Levakova V, Ocelka T, Pavliska L, Kovanic P, Klement GL. Addition of platelet concentrate to dermo-epidermal skin graft in deep burn trauma reduces scarring and need for revision surgeries. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014 Jun;158(2):242-58. doi: 10.5507/bp.2013.070. Epub 2013 Sep 27.
• Ruiz A, Cuestas D, Garcia P, Quintero J, Forero Y, Galvis I, Velasquez O. Early intervention in scar management and cutaneous burns with autologous platelet-rich plasma. J Cosmet Dermatol. 2018 Dec;17(6):1194-1199. doi: 10.1111/jocd.12554. Epub 2018 Apr 22.
• Asif M, Kanodia S, Singh K. Combined autologous platelet-rich plasma with microneedling verses microneedling with distilled water in the treatment of atrophic acne scars: a concurrent split-face study. J Cosmet Dermatol. 2016 Dec;15(4):434-443. doi: 10.1111/jocd.12207. Epub 2016 Jan 8.
• Klosova H, Stetinsky J, Bryjova I, Hledik S, Klein L. Objective evaluation of the effect of autologous platelet concentrate on post-operative scarring in deep burns. Burns. 2013 Sep;39(6):1263-76. doi: 10.1016/j.burns.2013.01.020. Epub 2013 Mar 5.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2020
• Primary Completion (Actual): May 24, 2021
• Study Completion (Actual): October 19, 2022

Study Registration Dates

• First Submitted: April 30, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 2, 2019

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: burn scar; hypertrophic scar; tissue repair; platelet rich plasma (PRP); vancouver scar scale (VSS); patient and observer scar assessment scale (POSAS)
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Fibrosis; Cicatrix; Hypertrophy; Cicatrix, Hypertrophic
• Other Study ID Numbers: IRB #190170

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: All reasonable efforts will be made to keep a patient's protected health information (PHI) private and confidential. Electronic records will be stored in restricted access database (Redcap, Vanderbilt) open only to the study team or on sponsor electronic databases which are password protected.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No