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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Brow Ptosis, Facial Scarring

Intervention / Treatment
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* Drug: 5-Fluorouracil
* Drug: Normal Saline Flush, 0.9% Injectable Solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients who undergo bilateral direct brow ptosis repair will be randomized to have one brow as the placebo arm and one arm as the active treatment arm. This original randomization will be maintained throughout the study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5-Fluorouracil Active Treatment Arm<br>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<br>* 50mg/ml concentration of 5-Fluorouracil to be injected intra-dermally in direct brow skin incisions<br>|
| Placebo Comparator: Placebo Arm<br>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<br>* 0.9% concentration of Normal Saline Injectable Solution to be injected intra-dermally in direct brow skin incisions<br>|

What is the study measuring?
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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 |