Post-Surgical Injection With Triamcinolone Versus Triamcinolone/Fluorouracil in Treatment of Keloids

Study Overview
=================
Brief Summary
-----------------
There have been many modalities utilized in the treatment of keloids of the head and neck, however none have been universally successful. The most widely utilized non-surgical intervention is primary intralesional injection with triamcinolone (TAC) which inhibits the proliferation of fibroblasts, inhibits collagen synthesis, and increases collagenase production, or fluorouracil (5-FU), a potent inhibitor of fibroblast proliferation. Despite the abundance of studies evaluating primary intralesional injection for keloids, there are limited studies available regarding the efficacy of primary surgical excision followed by adjuvant intralesional injection. The proposed study herein would serve to improve the level of evidence and to establish the safety and efficacy of combined intralesional TAC+5FU for keloids following surgical excision.

Detailed Description
-----------------
This is a single blinded, prospective randomized controlled trial of patients who elect for surgical treatment of keloids at the Center for Facial Plastic and Reconstructive Surgery at Our Lady of the Lake Regional Medical Center (OLOLRMC), a tertiary referral center affiliated with the Louisiana State University Health Sciences Center (LSUHSC) teaching system. Power analysis estimated approximately 134 patients total (67 per group) for 80% power to detect a difference at the 5% confidence level. This is based off of a prior group's study comparing primary intralesional injection with TAC vs TAC+5FU (no surgery). That study showed 39.2% recurrence with TAC vs 17.5% with TAC+5FU. The patients enrolled in the study will be randomized to one of two arms: surgical excision+TAC or surgical excision+TAC+5FU. Randomization will be performed using a permuted block randomization algorithm (Ex. AABBABABABBABBAA, where A=TAC only group and B=TAC +5FU). All patients will undergo surgical excision of the keloid, either under general anesthesia in the operating room or local anesthesia in the clinic setting depending on patient age and preference. The goal of excision will be complete extra-lesional excision with primary closure. It will be noted if a patient requires intra-lesional excision or additional reconstructive techniques such as advancement flap, skin grafting, or allografting (i.e. Integra). Monofilament sutures will be used preferentially to prevent local inflammatory reaction which can precipitate keloid formation. In group 1 (surgical excision+TAC), all patients will be treated with adjuvant intralesional TAC 40mg/mL 7-10 days post-op and then every 4 weeks for a total of 3 injections. The triamcinolone vial will be obtained from pharmacy and drawn up by the physician prior to injection. In group 2 (surgical excision+TAC+5FU), all patients will be treated with adjuvant intralesional TAC and 5FU at a dose of 0.1mg TAC for every 0.9mg 5FU 7-10 days post-op then every 4 weeks for a total of 3 injections. The mixture of TAC+5FU will be prepared by the pharmacy and delivered to the physician prior to injection. The goal volume of injection for both arms of the study will be 0.1cc per cm2 of scar excised, though any deviations from this and the rationale will be noted. Assessments will be performed at 3, 6, 9, and 12 months after completion of treatment. At each time point, a member of the study team and patient will complete their respective portion of the Patient and Observer Scar Assessment Scale (POSAS) which has been proven as a reliable and valid method of assessing keloid scars (5). The observer portion of the survey to be completed by the study team assesses vascularity, pigmentation, thickness, pliability, and surface area of the lesion. The patient portion of the survey focuses on the overall cosmetic and functional sequela including pain, itching, color, stiffness, thickness, and irregularity. Patients will also be asked about any side effects experienced. Each portion of the POSAS will be blinded from the study team member and the participant until both have completed the survey at each visit, so that one set of answers will not bias the other. If a patient demonstrates signs of recurrence or return of symptoms, there will be the option for additional injections within the patient's originally designated study arm. However, if early analysis demonstrates the alternative study arm to have superior efficacy, there will be the option to continue injections with the alternative study arm injection. Data collection will include demographic data such as age, gender, race, and Fitzpatrick skin type, as well as location of the keloid, etiology (trauma, post-surgical, etc.), and prior treatments if any. The size and thickness of each lesion, secondary defect size following adjacent tissue transfer, and amount of adjuvant medication injected during each adjuvant injection will be collected. Data analysis will include overall efficacy as well as stratification by variables such as the location of the lesion, size of the lesion, and prior treatment.

Official Title
-----------------
Efficacy of Post-Surgical Intralesional Injection With Triamcinolone Versus Triamcinolone Plus Fluorouracil in the Treatment of Keloids

Conditions
-----------------
Keloid, Keloid Scar Following Surgery

Intervention / Treatment
-----------------
* Drug: Triamcinolone Injection
* Drug: Triamcinolone Injection and 5-fluorouracil injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects of any age Subjects with at least one keloid of any size located in the head and neck region Exclusion Criteria: subjects with comorbidities prohibiting local injection of either TAC or 5FU including pregnancy, lactation, or planning pregnancy.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 cohort arms, single blinded; 1=TAC alone, 2=TAC+5FU
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TAC only<br>Participants will be treated with adjuvant intralesional TAC 40mg/mL 7-10 days post-op and then every 4 weeks for a total of 3 injections. Assessments will be performed at 3, 6, 9, and 12 months after completion of treatment. At each time point, a member of the study team and patient will complete their respective portion of the Patient and Observer Scar Assessment Scale (POSAS). | Drug: Triamcinolone Injection<br>* Post surgical injection at site of keloid with TAC for 3 injections<br>* Other names: TAC;|
| Active Comparator: TAC + 5FU<br>Participants will be treated with adjuvant intralesional TAC and 5FU at a dose of 0.1mg TAC for every 0.9mg 5FU 7-10 days post-op then every 4 weeks for a total of 3 injections. Assessments will be performed at 3, 6, 9, and 12 months after completion of treatment. At each time point, a member of the study team and patient will complete their respective portion of the Patient and Observer Scar Assessment Scale (POSAS). | Drug: Triamcinolone Injection and 5-fluorouracil injection<br>* Post surgical injection at site of keloid with TAC and 5FU for 3 injections<br>* Other names: TAC + 5FU;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Keloid Recurrence by visual assessment meaning either there is or is not a keloid physically present (determined by number of keloids observed and rate of recurrence after treatment) | Treatment effective if no keloid recurrence is visible by 12 months post treatment | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatology-assessed by Patient and Observer Scar Assessment Scale | Effectiveness of treatment on symptoms (pruritus, pain, hyperpigmentation or other side effects) as determined by changes in the POSAS survey (1 being not observed to 10 being present always and also by visual assessment by the physician | 3 months |