The Role of 5-Fluorouracil in Post-Operative Scar Formation Following Direct Brow Ptosis Repair

This is a double (physician and patient) blinded randomized controlled clinical trial in which patients who have undergone bilateral direct brow ptosis repair undergo a trial in which one of brow is injected with placebo 0.9% Normal Saline and the contra-lateral brow is injected with 0.3-0.6 mL over the entire brow of 50mg/mL 5-Fluorouracil sub-dermal injections. The researchers aim to investigate whether injecting 5-Fluorouracil preemptively will not only accelerate wound healing and decrease hypertrophic scar formation compared to placebo, but also improve overall scar appearance in a safe manner.

Study Overview

• Status: Unknown
• Conditions: Brow Ptosis; Facial Scarring
• Intervention / Treatment: Drug: 5-Fluorouracil; Drug: Normal Saline Flush, 0.9% Injectable Solution

Detailed Description

In this double-blinded (physician and patient) randomized controlled clinical trial, the patient's left and right brows are randomized to either the placebo or treatment arm of the study and maintain this designation for the entirety of the study. This randomization is performed and recorded by the study nurse in the physician's office. This study nurse also will be responsible for preparing the placebo 0.9% Normal Saline (0.9%NS) and the 50mg/mL 5-Fluorouracil (5-FU). Both placebo and 5-FU are placed into identical syringes with 30 gauge needles, both materials are identical in color and clarity, making it impossible for physician or patient to correctly identify which injection is which without a label. Only the study nurse will be aware of which injection is which, and the nurse will ensure that the correct injection is placed into the correct brow at each visit via the study log that the nurse maintains.

A patient who has undergone bilateral direct brow ptosis repair who has agreed to participate in the study will first return for the post-operative day 10 visit where sutures are removed from the brow incisions. The patient returns on post-operative week three for their first injections, the details of which are below:

Starting on post-operative week three, the patient will receive 0.05mL aliquots of each injection (0.9%NS and 5-FU) sub-dermally into the brow incision spread out evenly over the brow, totaling 0.3-0.6 mL of each injection over each respective brow. Photos of the patient's brows will be taken, and then both the physician and patient will fill out a survey recording their impressions, the contents of which are listed in subsequent sections of this protocol. This same procedure will be repeated every three weeks for a total of up to four rounds of injections, thus the final round of injections will be given on post-operative week twelve. At each of these post-operative visits, incidence of any side effects is recorded, and if an unacceptably high rate of side effects occurs, the study will be precociously terminated.

At post-operative week fifteen, the blind is broken, and again photos are taken and physician and patient impressions are recorded via survey. After the blind is broken, if desired, the patient can opt to undergo a similar series of injections on the placebo arm of 5-FU.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Houma, Louisiana, United States, 70363
      • Leonard J. Chabert Medical Center
    • New Orleans, Louisiana, United States, 70115
      • Eyelid and Facial Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who have undergone bilateral direct brow ptosis repair (either cosmetic of functional)

Exclusion Criteria:

• Known prior knowledge of the study's existence
• History of hypertrophic scarring
• Prior brow surgery, prior incisions or trauma to the forehead, brow or peri-ocular area in the past
• Patients who are decisionally or mentally impaired as they will be required to fill out the supplied survey and have the capacity for consent for the treatment
• Patients with any disease which may affect the brow (e.g. Myasthenia Gravis)
• Actively being treated for malignancy
• Uncontrolled autoimmune diseases with skin involvement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5-Fluorouracil Active Treatment Arm; A patient who has undergone bilateral direct brow ptosis repair and has elected to participate in the study will first have each of their brows randomized to either be the active treatment arm or the placebo arm. The active treatment arm brow will be injected with 0.05ml of 5-Fluorouracil 50mg/ml in several injections evenly spaced over the brow incision for a total of 0.3-0.6ml, repeated every three weeks for a total of 4 series of injections.	Drug: 5-Fluorouracil; 50mg/ml concentration of 5-Fluorouracil to be injected intra-dermally in direct brow skin incisions
Placebo Comparator: Placebo Arm; A patient who has undergone bilateral direct brow ptosis repair and has elected to participate in the study will first have each of their brows randomized to either be the active treatment arm or the placebo arm. The placebo arm brow will be injected with 0.05ml of 0.9% Normal Saline in several injections evenly spaced over the brow incision for a total of 0.3-0.6ml, repeated every three weeks for a total of 4 series of injections.	Drug: Normal Saline Flush, 0.9% Injectable Solution; 0.9% concentration of Normal Saline Injectable Solution to be injected intra-dermally in direct brow skin incisions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall appearance	Patient and physician impression of overall appearance of the direct brow incision scar	1 year
Skin tone match	Patient and physician impression of how close the direct brow incision scar matches the patient's natural skin tone/color	1 year
Scar roughness/tough to touch	Patient and physician impression as to the degree of rough to the touch (ie fibrosis) is present in the direct brow incision scar	1 year
Scar is flush with eyebrow	Patient and physician impressions as to degree that direct brow incision scar is flush with skin of the brow	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of side effects	Any incidence of any side effects	1 year

Collaborators and Investigators

• Sponsor: Eyelid and Facial Consultants
• Collaborators: Ochsner Health System
• Investigators: Principal Investigator: Adham B. al Hariri, M.D., Eyelid and Facial Consultants New Orleans

Publications and helpful links

General Publications

• Poetschke J, Gauglitz GG. Current options for the treatment of pathological scarring. J Dtsch Dermatol Ges. 2016 May;14(5):467-77. doi: 10.1111/ddg.13027.
• Wendling J, Marchand A, Mauviel A, Verrecchia F. 5-fluorouracil blocks transforming growth factor-beta-induced alpha 2 type I collagen gene (COL1A2) expression in human fibroblasts via c-Jun NH2-terminal kinase/activator protein-1 activation. Mol Pharmacol. 2003 Sep;64(3):707-13. doi: 10.1124/mol.64.3.707.
• Yoo DB, Azizzadeh B, Massry GG. Injectable 5-FU with or without added steroid in periorbital skin grafting: initial observations. Ophthalmic Plast Reconstr Surg. 2015 Mar-Apr;31(2):122-6. doi: 10.1097/IOP.0000000000000214.
• Gupta S, Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatology. 2002;204(2):130-2. doi: 10.1159/000051830.
• Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, Stefanaki K, Argyrakos T, Petridis A, Katsambas A. Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study. J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):474-9. doi: 10.1016/j.jaad.2004.09.018.
• Fang QQ, Chen CY, Zhang MX, Huang CL, Wang XW, Xu JH, Wu LH, Zhang LY, Tan WQ. The Effectiveness of Topical Anti-scarring Agents and a Novel Combined Process on Cutaneous Scar Management. Curr Pharm Des. 2017;23(15):2268-2275. doi: 10.2174/1381612822666161025144434.
• Khan MA, Bashir MM, Khan FA. Intralesional triamcinolone alone and in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. J Pak Med Assoc. 2014 Sep;64(9):1003-7.
• Darougheh A, Asilian A, Shariati F. Intralesional triamcinolone alone or in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars. Clin Exp Dermatol. 2009 Mar;34(2):219-23. doi: 10.1111/j.1365-2230.2007.02631.x. Epub 2008 Nov 6.
• Huang L, Cai YJ, Lung I, Leung BC, Burd A. A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro. J Plast Reconstr Aesthet Surg. 2013 Sep;66(9):e251-9. doi: 10.1016/j.bjps.2013.06.004. Epub 2013 Jun 28.
• Pomerantz H, Hogan D, Eilers D, Swetter SM, Chen SC, Jacob SE, Warshaw EM, Stricklin G, Dellavalle RP, Sidhu-Malik N, Konnikov N, Werth VP, Keri J, Lew R, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial Group. Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial. JAMA Dermatol. 2015 Sep;151(9):952-60. doi: 10.1001/jamadermatol.2015.0502.
• Jones CD, Guiot L, Samy M, Gorman M, Tehrani H. The Use of Chemotherapeutics for the Treatment of Keloid Scars. Dermatol Reports. 2015 May 21;7(2):5880. doi: 10.4081/dr.2015.5880. eCollection 2015 May 21.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2017
• Primary Completion (Anticipated): April 30, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: July 13, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Prolapse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: LSUIRB#9586

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