A Single Center, Double-blinded Randomized Placebo-controlled Trial to Evaluate Surgical Scars After Treatment With Fractional Carbon Dioxide Rejuvenation Laser Therapy
Phase: NA
Conditions: Cicatrix, Carbon Dioxide Laser
Sponsor: St. Louis University

A single center, double-blinded randomized
placebo-controlled trial to evaluate surgical scars after
treatment with fractional carbon dioxide rejuvenation laser
therapy
NCT02985151
Approved: 28 November 2016

1 
 
 
 
 
A single center, double-blinded randomized placebo-controlled trial to evaluate surgical scars after 
treatment with fractional carbon dioxide rejuvenation laser therapy 
 
Version 1 
IRB # 27403 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
Table of Contents  
Synopsis……………………………………………………………………………………………………………………………………..4 
Study Timeline…………………………………………………………………………………………………………………………….4 
Introduction………………………………………………………………………………………………………………………………..4 
Study Objectives/Primary and Secondary……………………………………………………………………………………5  
Selection and Withdrawal of Subjects…………………………………………………………………………………………5 
Study Population……………………………………………………………………………………………………………5 
Inclusion and Exclusion Criteria…..…………………………………………………………………………………6 
Subject Discontinuation or Withdrawal from Study Participation………………….………………6 
 
Subject Discontinuation……………………………………………………………………………………6 
 
Screen Failures…………………………………………………………………………………………………7   
Study Device: CO2RE Laser…………………………………………………………………………………………...7   
Mechanism of Action……………………………………………………………..…….………………....7 
Dose Regimen………………………………………………………………………………………………….7 
Study Device: Vectra Imaging System…………………………………………………………………………...7  
Study Procedures………………………………………………………………………………………………………….8 
Visit Flowchart…………………………………………………………………………………………………9 
Visit #1…………………………………………………………………………………………………………….9 
Visit #2…………………………………………………………………………………………………………….11 
Visit #3…………………………………………………………………………………………………………….11 
Visit #4…………………………………………………………………………………………………………….12  
Visit #5…………………………………………………………………………………………………………….13 
Unscheduled Visits…………………………………………………………………………………………..13 
Completion of Study………………………………………………………………………………………..13  
Methods of Assigning Subjects to Treatment Arms……………………………………………………….13 
Blinding……………………………………………………………….……………………………………………13  
Unblinding……………………………………………………………………………….……………………….13  
Concomitant Treatments………………………………………………………………………………………………14 
Prohibited………………………………………………………………………………………………...........14  

3 
 
 
Permitted………………………………………………………………………………………………………….14  
Benefits and Alternatives……………………………………………………………………………………………….14  
Safety…………………………………………………………………………………………………………………………….14 
Early Study Termination…………………………………………………………………………………………………15 
 
Adverse Events………………………………………………………………………………………………………………15 
 
 
Definition of Adverse Events…………………………………………………………………………….15 
 
 
Reporting of Adverse Events…………………………………………………………………………….15 
 
 
Intensity Grading………………………………………………………………………………………..…….16  
 
 
Causality and Relatedness…………………………………………………………………………………16  
 
Serious Adverse Event……………………………………………………………………………………………………16 
 
 
Definition of Serious Adverse Events…………………………………………………………………16 
 
 
Reporting Serious Adverse Events…………………………………………………………………..…17 
Death Events……………………………………………………………………………………………………………………………...17  
Reporting of Pregnancy…………………………………………………………………………………………..………………….17 
Data Analysis and Statistical Considerations……………………………………………………………………………….17  
Quality Control and Quality Assurance……………………………………………………………………………………….18  
Direct Access, Data Handling and Record Keeping……………………………………………………………………..18 
Confidentiality……………………………………………………………………………………………………………………………18 
Data Protection………………………………………………………………………………………………………………………….18  
Records Retention……………………………………………………………………………………………………………………..18  
Posting to Clinical Trials Register and Publication………………………………………………………………………18  
 
 
 
 
 
 
 
 
 

4 
 
Synopsis  
This study evaluates the effect of a fractionated carbon dioxide laser on surgical scars of the 
face and neck over 12 months. Anyone with a surgical scar on the face and neck who has not 
had laser therapy may be eligible. The visits occur every three months for up to 12 months. Subjects will 
be randomly assigned to receive two high energy treatments or two low energy treatments. During the 
study visits, the scars will be photographed pre-treatment and the subject will complete a questionnaire 
to rate the scar. Three physicians will also evaluate the scar: one as a live assessment and the other two 
will evaluate the scars after each visit using photographs. Patients will receive their assigned treatment, 
obtain post-treatment instructions, and a diary to record redness, swelling, pain, itching, or other skin 
changes after treatment. Patients and raters will be blinded to which therapy level the patient receives 
until the 9-month visit (Visit #3) at which time patients will be unblinded and offered to have a third high 
energy treatment if in the high energy treatment group or to have two high energy treatments if in the 
low energy treatment group.  
 
Study Timeline 
The study will occur over 14 months. Our tentative timeline consists of recruitment and 
screening to occur in November 2016-September 2017. Study visits and data collection would occur 
between November 2016 and September 2017. Preliminary data analysis and publication of preliminary 
results would occur between August 2017 and March 2018. Final data analysis and publication would be 
between October 2018 and January 2019. 
Introduction  
In dermatology, the use of Light Amplification by Stimulated Emission of Radiation (laser) has 
revolutionized the management of various conditions including angiomas, vitiligo, wrinkles, and 
scars. (Omi, 2014 and Chapas, 2008) Scars result from sub-optimal collagen production during 
wound healing leading to topographical irregularities. In addition to impairing body image, these scars 
may limit functional recovery, compromise activities of daily living, and prevent return to work. To 
effectively modify these defects, any treatment must be capable of penetrating the epidermis and 
eliciting dermal remodeling at a depth of at least 1 mm. (Chapas, 2008) Laser ablation removes 20 to 60 
μm of epidermis and heats a zone of connective tissue approximately 120 μm wide, resulting in 
vaporization of the upper layers of the dermis to create a wound bed optimal for new collagen and 
elastin formation. Re-epithelialization occurs over 7-to-14 days, thus rejuvenating the patient’s skin. 
(Omi, 2014; Bordenorf, 2009; Chapas, 2008) The 10,600 nm carbon dioxide (CO2) laser 
utilizes high energy at short durations to vaporize intra- and extra-cellular water, resulting in 
tissue ablation causing a substantial thermal injury to the dermis, reducing the likelihood of 
additional scarring (Chapas, 2008). The incorporation of fractional photothermolysis, first 
introduced by Manstein et, al. facilitates a controlled area of dermal injury creating cylindrical 
microscopic treatment zones (MTZ) of necrosis (Hong Li, 2010, Manstein et al, 2004). Sparing 
uninvolved normal healthy tissue, each wound is surrounded by healthy cells that can migrate 
towards the wound, allowing for faster healing by secondary intention (Manstein et al, 2004). 
The fractionated CO2 laser is selective in that segments of tissue are effected, which translates 
into decreased recovery time (downtime) for the patient (Bordenorf, 2009). Therefore, by 
causing selective thermal injury in the skin, the CO2 laser can stimulate collagen production 
and theoretically improve scar thickness, pliability, and texture. 
 
The utility of the CO2 laser was first examined in patients with wrinkles. In a split face 

5 
 
prospective cohort study of 20 Chinese women, blinded evaluators and patients agreed at one 
and three months post-CO2 laser resurfacing that the deep wrinkles on the faces of subjects 
were more shallow, pores smaller, texture more smooth, and skin appeared brighter compared 
to the untreated side. Additionally, there was a perpetual decrease in the roughness of treated 
skin by 9.72% on day 7 post treatment, 18.92% at 1 month follow-up, and 24.40% at 3 months 
assessed by a 3-D in-vivo imaging system (Hong Li, 2010). Likewise, CO2 laser resurfacing for 
acne scars yielded similar positive outcomes. Chapas et al performed an unblinded cohort 
study of 13 patients with moderate to severe acne scarring to evaluate change in acneiform 
scars following two to three treatments with ablative laser resurfacing with a 30 W CO2 Fraxel 
re:pair laser. She observed that subjects and investigators rated 26-50% improvement in 
atrophy and cheek scarring three months after laser treatment. Use of the Phaseshift Rapid In 
Vivo Measurement (PRIMOS) topographical skin imaging system demonstrated that the mean 
depths of scars improved by 66.8%. With higher energy levels (70-100 mJ) on 
deeper scars on the cheek after the second and third treatment, scars improved by 51-75% 
three months after the final treatment (Chapas et al, 2008). In another study using a cohort of 60 
patients with various morphologies of acne scars over three years with 3-4 sessions, a blinded 
evaluator rated 67% of patients with good-to excellent improvement in their overall appearance 
compared to images of their pre-treatment status (Majid, 2014). 
 
Our study is a prospective, randomized double-blinded placebo-controlled trial to evaluate the 
efficacy of fractionated carbon dioxide laser in improving surgical scars on the head and neck. 
Scar assessments will be based on objective changes identified with the Canfield Vectra M3 3D Imaging 
System and subjective changes identified with the Patient and Observer Scar Assessment Scale (POSAS), 
a validated scar scale. 
 
Study Objectives/Primary and Secondary 
The primary objective is to assess the efficacy of fractionated carbon dioxide laser in improving 
surgical scars. Objective assessment of the scars will involve the Vectra microtopographic 
imaging system to measure changes in the length of the scar. The Patient and Observer Scar 
Assessment Scale (POSAS) is a validated survey that will be utilized for subjective assessments of the 
vascularity, pigmentation, thickness, pliability, surface area, relief, pain, and pruritus. 
 
The secondary objective will be to evaluate the tolerability of the laser, by assessing the 
severity and duration of known side effects of laser therapy such as erythema, edema, burning 
sensation, post-inflammatory pigment changes, infection, scarring, xerosis, pruritus, bronzing, 
and any other adverse events that arise following treatment. Patients will be given a 30-diary after 
each treatment to document this information. 
 
Selection and Withdrawal of Study Subjects  
Study Population  
The study population will consist of 50 adult patients 18 years of age or older with surgical scars 
located on the head and neck. 
Minors are not included due to the Mohs patient population being adults only who have 
undergone surgical excisions of skin cancers on the head or neck.  Although participants are not 

6 
 
required to be patients in the Mohs clinic, scars and healing may be significantly different in children, 
making the data less reliable and difficult to interpret. 
Inclusion and Exclusion Criteria  
For the inclusion criteria, adult patients of all Fitzpatrick phototypes who have surgical scars of 
the head and neck will be screened for this study. There is no data to suggest that there is a difference in 
the appearance of older (more than 1 year old from the initial injury) and newer scars (at least 8 weeks 
after surgery) post-therapy. Most scars are fully mature at exactly 1 year from the date of the initial 
injury, so in the “older scar” cohort one may presume (in the absence of any confirmed findings in the 
medical literature) that any changes to these scars post-therapy will be an effect from the laser.  The 
minimum age of the scar will be eight weeks from the initial surgery, as the scar has healed enough to 
determine if additional fine tuning may be helpful.  In addition, standard practice is to allow a scar to 
heal for 8 weeks before laser treatment. Therefore subjects may be enrolled in the younger scar group if 
the scar is 8 weeks – 51 weeks from occurrence, and enrolled in the older scar group if the scar is 52 
weeks or older from time of occurrence. We will aim to recruit 20 patients with old scars (10 of which 
will be in the high energy treatment group, and 10 of which will be in the low energy treatment group). 
In terms of statistical analysis, we will review whether there is a difference between the post-treatment 
measurements and appearance of older scars and newer scars. Patients must be able to understand the 
informed consent, willing to come to the office for treatments and capable of following post-treatment 
instructions.  
In terms of exclusion criteria, patients who have had prior laser treatments to the face and neck, 
have a history of keloid formation, scars resulting from non-surgical etiologies (i.e. minor trauma), 
isotretinoin use in the last 6 months prior to study enrollment, and allergy to topical lidocaine will not be 
eligible for the study.  
Minors are not included due to the Mohs patient population of adults only who have undergone 
surgical excisions of skin cancers on the head or neck.  Although participants are not required to be 
patients in the Mohs clinic, scars and healing may be significantly different in children, making the data 
less reliable and difficult to interpret. Any patient who has a condition that the PI assesses may put the 
subject at significant risk, may confound the study results, or may interfere significantly with the 
subject's participation in the study will be excluded from the study. Pregnant subjects are not included 
in the study due to insufficient data on the safety of lasers in pregnant patients.  
 
Subject Discontinuation or Withdrawal from Study Participation  
Subject Discontinuation  
At any time within the trial, subjects may discontinue participation.  Subjects who do not 
complete the trial will be asked to identify the reason for discontinuation and this information will be 
documented. If the date that they elect to discontinue from the trial occurs shortly after a treatment 
(within minutes to 30 days after treatment), patients will be asked to return for a follow-up 3 months to 
evaluate for any significant adverse events. No treatments will be performed. Only photographs of the 
scar and rating of the scar by the patient and evaluators will be performed at this visit. Also, collection of 
the diary will occur at this visit.  If subjects discontinue from the trial after 30 days, patients will be 
followed up via phone for the reason of their discontinuation and asked to return the diary as soon as 

7 
 
possible. In either case, subjects will be given the contact information for the research office in case they 
have further concerns regarding their participation in the trial.  
There are no guidelines or endpoints by which early decisions regarding efficacy or lack of efficacy will 
be made for this FDA approved device. However, the PI could stop the study early if significant 
unexpected adverse events occur, or enrollment and retention is not adequate.   
Screen Failures  
 
Subjects who do not meet the eligibility criteria will be considered screen failures. Any 
documentation completed prior to the determination of their status will be placed in one of the 
containers for shredding in our facility. The reason for the disqualification will be noted and the subject 
will be included in the count for screened subjects for publication purposes.  
Study Device: CO2RE Laser  
This fractionated ablative laser is FDA approved for the revision of surgical scars. Access to this laser may 
also be obtained outside of the study.   
Mechanism of Action 
The 10,600 nm carbon dioxide (CO2) laser utilizes high energy at short durations to vaporize 
intra- and extra-cellular water, resulting in tissue ablation causing a substantial thermal injury to the 
dermis, reducing the likelihood of additional scarring (Chapas, 2008). The incorporation of fractional 
photothermolysis, first introduced by Manstein et, al. facilitates a controlled area of dermal injury 
creating cylindrical microscopic treatment zones (MTZ) of necrosis (Hong Li, 2010, Manstein et al, 2004). 
Sparing uninvolved normal healthy tissue, each wound is surrounded by healthy cells that can migrate 
towards the wound, allowing for faster healing by secondary intention (Manstein et al, 2004). 
The fractionated CO2 laser is selective in that segments of tissue are effected, which translates 
into decreased recovery time (downtime) for the patient (Bordenorf, 2009). Therefore, by 
causing selective thermal injury in the skin, the CO2 laser can stimulate collagen production 
and theoretically improve scar thickness, pliability, and texture. 
 
Dose Regimen 
  
Subjects will be randomized to either a high energy treatment (CO2RE Mid treatment mode [45-
257 mJ] or CO2RE Deep treatment [30-70 mJ] mode) or a low energy treatment (CO2RE Light treatment 
mode [18-74.5 mJ] mode).   
Study Device: Canfield Vectra M3 Imaging System  
 
This body imaging is utilized in several clinical trials to capture 3-D photographs of subjects. 
Subjects will have images and dimensions of their scars measured in a non-invasive manner at each visit 
using photographs taken with the Canfield Vectra M3 3D Body Imaging System.  Detailed step-by-step 
instructions for executing the images and measuring the scars will be a separate document.  
 
 

8 
 
Study Procedures 
A screening visit will occur whereby patients deemed appropriate for the study will have the 
segment of the scar with the most deformity defined for objective evaluation at each session. Baseline 
photographs of this area will be obtained and demographic data about the surgery that created the scar, 
associated wound healing complications, age of the scar, and the Fitzpatrick skin phototype will be 
collected. Randomization will occur at this visit and patients will receive their first treatment at this visit. 
Prior to treatment application, subjects will cleanse their face with a gentle cleanser, such as Cetaphil, 
provided in the office in order to remove all lotion, creams, make up, and sunscreen.  An optional topical 
or local anesthetic medication will be offered to the subject and if desired by the subject will be applied 
to the treatment area approximately 20 minutes prior to the procedure. If the scar is deeper, an 
injection of numbing medicine (lidocaine with epinephrine) may be used as well. Once this time passes 
and the numbing medicine is working, the subject will be escorted to the procedure room. The 
treatment areas will be wiped clean of the numbing cream prior to the procedure. Just prior to the 
procedure, the subject’s eyes will be covered with eye shields to protect their eyes. The treatment time 
may vary, but generally takes 10 minutes or less. During this time, subjects will hear the laser, which 
sounds like a bee buzzing, and will feel some warmth. Most patients report minimal discomfort during 
the procedure. There may be pinpoint bleeding, bruising, and crusting depending upon the area and 
extent of the treatment.  After the treatment, patients will be provided with a 30-day diary to daily 
record treatment-related reactions: redness, swelling, pain, itching or color changes following 
treatment. If the subject has a history of recurrent fever blisters/cold sores on the lips or face, the 
subject will be offered a three day prescription for an antiviral medication that the subject can fill at the 
subject’s pharmacy to prevent a recurrence since laser treatments may increase the chance of recurrent 
episodes. The subject would take one pill every twelve hours the day prior to treatment, on the 
treatment day, and the first day post-treatment. The subject or their insurance plan must cover the cost 
of the medication.  This may delay the treatment to a later date within 30 days of the screening visit. If 
antibiotic/antiviral medications are needed, you and/or your insurance company will be responsible for 
covering this cost. 
 
 If a patient prefers not to have treatment at this visit, they will be asked to return to clinic for this first 
treatment within 30 days from the screening and randomization visit. Subjects will return for a second 
treatment 3 months later. With 10 min allotted for treatment, as well as completing the patient 
questionnaire (5-7 minutes), assessment of adverse events and updating medications and procedures, 
along with performing photographs  (10 min) and having an evaluation by the blinded evaluator, the 
entire visit may take up to 30-40 min.   The diary entries will take 5 minutes each day.   Subjects will 
return again 3 months following the second treatment and will undergo the follow up photos and 
assessments. Subjects will be unblinded at the third visit to the treatment received and given three 
options. One option is to exit from the study. The second option is if the subject received the high 
energy laser treatments, the subject may elect one additional treatment that day. The third option is 
subjects with low energy treatments have the option to receive two high energy treatments at this visit 
and a subsequent visit. Those in the high energy group who receive the third optional high energy 
treatment will return in 3 months for an exit visit and follow-up assessment of the scar (photos, patient 
POSAS, and observer POSAS) and exit at visit #4. Those in the low energy group who elect the two high 
energy treatments will follow up in 3 months after Visit #3 for the final high energy treatment, photos, 
and assessments (patient POSAS and observer POSAS). After receiving the last optional high energy 
treatment at Visit #4, patients in this low energy treatment group will return to the clinic in 3 mos for 
the last study visit where pictures will be obtained, survey assessments of the scar will occur, and the 

9 
 
subject will exit from the study. This allows comparison of all subjects following 2 treatments, and adds 
further data to the high energy laser treatment group for subjects who cross over. 
The subjects’ participation may be up to 14 months.  
 
Visit Flowchart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Visit #1 
The subject will verify information regarding the subject’s name and contact information. The subject 
cannot take part in this study if the subject has a history of prior laser treatment to the face or neck, or if 
Visit #1: Screening & 
Randomization (if not on same 
day, must be within 30 days) & 
Treatment 
Visit #2 (High energy treatment) 
Visit #2 (Low energy treatment 
group) 
Visit #3 (Unblinding of low energy 
treatment group) 
Visit #3 (Unblinding of high energy 
treatment group) 
Elect 
optional two 
HIGH energy 
treatments 
(receive 1 
high energy 
treatment)   
 
Exit study  
Elect one  
optional HIGH 
energy 
treatment 
Visit #4 (receive 2nd 
high energy 
treatments) 
Visit #4 exit visit for 
three treatments of 
high energy  
Visit #5 
Exit study  

10 
 
the subject tends to form keloid scars or scars from minor trauma. Also, the subject should not 
participate in the study if the subject has taken oral isotretinoin medication within the past 6 months. In 
addition, the principle investigator may exclude the subject from the study if she determines that the 
study may put the subject at risk. The subject will provide written consent (permission) to be a 
participant in the study and for the research team to access the subject’s health information to learn 
more about the surgery that resulted in the scar and the original features of the scar.  Immediately 
before any study visit, the subject will be asked to not wear any make-up or use facial moisturizers (or 
moisturizers on the neck). The subject will be asked to cleanse their face with a gentle cleanser, such as 
Cetaphil, provided in the office prior to treatment. 
Other procedures at this visit: 
 
The subject will have photographs taken of the scar that will be shared confidentially with two 
other research physicians in the study for them to answer questions about the scar.  
 
The subject will complete a questionnaire about the scar and another research physician will see 
the subject at this visit to evaluate the scar.  
 
If the subject qualify for study treatment the following may occur at the same visit or at a return visit 
within 30 days. The following will occur: 
 
If the subject has a history of recurrent fever blisters/cold sores on the lips or face, The subject 
will be offered a three day prescription for an antiviral medication that the subject can fill at the 
subject’s pharmacy to prevent a recurrence  since laser treatments may increase the chance of 
recurrent episodes. The subject would take one pill every twelve hours the day prior to 
treatment, on the treatment day, and the first day post-treatment. The subject or their 
insurance plan must cover the cost of the medication.  This may delay the treatment to a later 
date within 30 days of the screening visit. 
 
 
The subject will complete a pre-treatment questionnaire. 
 
The subject will receive laser treatment as randomized to either high energy or low energy 
treatment which includes: 
o Prior to treatment, the subject will be asked to cleanse his or her face with a gentle 
cleanser, such as Cetaphil, provided in the office in order to remove all lotion, creams, 
make up, and sunscreen. 
o A topical anesthetic medication will be applied to the treatment area approximately 20 
minutes prior to the procedure. If the scar is deeper, an injection of numbing medicine 
may be used as well. Once this time passes and the numbing medicine is working, the 
subject will be escorted to the procedure room. The treatment areas will be wiped clean 
of the numbing cream prior to the procedure.  
o Just prior to the procedure, the subject’s eyes will be covered with eye shields to protect 
their eyes.  
o The treatment time may vary, but generally takes 10 minutes or less. During this time, 
the subject will hear the laser, which sounds like a bee buzzing, and will feel some 
warmth. Most report minimal discomfort during the procedure. There may be pinpoint 
bleeding, bruising, and crusting depending upon the area and extent of the treatment. . 
After the treatment, the subject will be provided with a diary to daily record treatment-
related reactions: redness, swelling, pain, itching or color changes following treatment.  
o The subject will be given a paper diary to record possible reactions such as redness, 
swelling, pain, itching or color changes following treatment 

11 
 
o You will be given post-treatment instructions: 
o Thoroughly wash your hands prior to touching the treatment area.  
o Gently clean the treated area with a mild cleanser 3 times per day. Splash the 
face with tepid water and pat dry with a paper towel or a clean soft washcloth. 
The goal is to lightly remove the exfoliating skin and crusting that develops after 
the laser procedure. This is a GENTLE process with NO scrubbing. Avoid picking 
or scratching at the treatment site, as the skin is very friable and sensitive. 
Picking or scratching can lead to pigmentation changes or further scarring.  
o After each cleaning, apply a coat of Vaseline with a cotton tipped applicator (i.e. 
Q-tip) 
o As the skin heals, it is common to see little dots (“peppering”) all over the 
treated skin. These will come off with the cleansing process. 
o You will continue the wound care for 7 - 10 days, at which time you should 
begin applying sunscreen instead of Vaseline. 
o You can shower the next day and wash hair, but avoid very hot water 
o Do not expose the treated area to sun or wind for at least two weeks after 
treatment. If you go outside, use sunscreen with zinc (SPF 30+) and wear a hat. 
Protecting your skin and limiting sun exposure ensures the best results. 
o Expect the treated area to be red for several weeks. You can use makeup 
starting three days after the treatment, but it is best to wait until the skin has 
fully exfoliated and becomes pink to red shiny, smooth skin. This usually takes 7 
to 10 days. 
o Some swelling may develop, and generally lasts 1-2 days. It is recommended 
that you sleep in a slightly elevated position to help relieve swelling. 
o It is common to feel a heat or sunburn sensation in the treated areas. This heat 
will dissipate over the next few hours. Cold compresses, such as ice, may help 
soothe the heat and can be gently applied to the skin. 
o Pain is uncommon after the first few days, and usually subsides with Tylenol and 
cooling the skin. Itching can be seen, and will usually last a few days or less. You 
can press on the clean itchy skin with a cotton tipped applicator (i.e. Q-tip) to 
relieve the itching. Avoid scratching the skin. 
o Normal daily activities may be resumed immediately after treatment. Avoid 
strenuous exercise, bending, straining, stooping or lifting heavy objects for 48 
hours. These activities may cause swelling and pain in the treatment area. If a 
patient is not able to receive the treatment on the same day as the screening 
and randomization visit (possibly due to an ongoing oral herpetic infection), 
they may return to the office within 30 days for their first treatment.  
Study Visit #2 
The subject will be asked to return in 3 months for a second treatment visit with the following activities: 
o The subject will complete a pre-treatment questionnaire 
o The subject will receive laser treatment as randomized to high energy or low energy treatment 
o The subject will obtain post-treatment instructions 
o The subject will  obtain a paper diary to record possible reactions such as redness, swelling, 
pain, itching or color changes following treatment 
o If the subject has a history of recurrent fever blisters/cold sores on the lips or face, the subject 
will be offered a three day prescription for an antiviral medication that the subject can fill at the 
subject’s pharmacy to prevent a recurrence  since laser treatments may increase the chance of 
recurrent episodes. The subject would take one pill every twelve hours the day prior to 

12 
 
treatment, on the treatment day, and the first day post-treatment. The subject or their 
insurance plan must cover the cost of the medication.  This may delay the treatment to a later 
date within 30 days of the screening visit. 
 
Study Visit #3 
This visit occurs 3 months after the subject’s second treatment with the following activities: 
o The subject will return the diary 
o The subject will complete a questionnaire 
o The subject will undergo scar evaluation by the research physician 
o The subject will have photographs taken 
o The treating investigator will let the subject know which treatment the subject received 
o If the subject received the high energy laser treatment, the following will occur: 
o The subject will be offered the option to receive a third high energy treatment.  
o If the subject accepts treatment today, the subject will return in 3 months for the final 
follow up visit and to exit the study 
o If the subject declines further treatment, the subject will be exited from the study at this visit. 
 
If the subject received the low energy laser treatment, the following will occur:  
o The subject will be offered the option to receive two high energy treatments.  
o If the subject accepted treatment, the subject will receive one treatment today and 
return in 3 months for the second treatment (Visit 4); the subject will then be asked to 
return 3 months later for a follow up final study visit (Visit 5). 
o If the subject declined further treatment, the subject will be exited from the study. 
 
Study Visit #4 
If the subject were originally treated with the high energy laser, and elected a third treatment at Visit 3, 
this visit occurs 3 months after the subject’s Visit 3 treatment with the following activities: 
o The subject will return the subject’s diary 
o The subject will complete a questionnaire 
o The subject will undergo scar evaluation by the research physician 
o The subject will have photographs taken 
o The subject will be exited from the study 
 
If the subject were originally treated with the low energy laser, and elected treatment with the high 
energy laser, this visit occurs 3 months after the subject’s Visit 3 treatment with the following activities: 
o The subject will complete a pre-treatment questionnaire 
o The subject will receive the last high energy laser treatment The subject will obtain post-
treatment instructions 
o The subject will  obtain a paper diary to record possible reactions such as redness, swelling, 
pain, itching or color changes following treatment 
o If the subject has a history of recurrent fever blisters/cold sores on the lips or face, the subject 
will be offered a three day prescription for an antiviral medication that the subject can fill at the 
subject’s pharmacy to prevent a recurrence  since laser treatments may increase the chance of 
recurrent episodes. The subject would take one pill every twelve hours the day prior to 
treatment, on the treatment day, and the first day post-treatment. The subject or the subject’s 
insurance plan must cover the cost of the medication.  This may delay the treatment to a later 
date within 30 days of the screening visit. 
o The subject will be asked to return in 3 months for a final follow- up visit 

13 
 
 
Study Visit #5 
This visit occurs 3 months after the subject’s last treatment if the subject received the low energy laser 
treatment followed by the high level laser therapy as a final study visit. The subject will not be offered 
treatment at this follow up visit. The following will occur: 
o The subject will return the subject’s diary 
o The subject will complete a questionnaire 
o The subject will undergo scar evaluation by the research physician 
o The subject will have photographs taken. 
 
At any time, the subject may choose to not participate in the study. If the date that they elect to 
discontinue from the trial occurs shortly after a treatment (within minutes to 30 days after treatment), 
patients will be asked to return for a follow-up 3 months to evaluate for any significant adverse events. 
No treatments will be performed. Only photographs of the scar and rating of the scar by the patient and 
evaluators will be performed at this visit. Also, collection of the diary will occur at this visit.  If subjects 
discontinue from the trial after 30 days, patients will be followed up via phone for the reason of their 
discontinuation and to assess for AE/SAEs and asked to return the diary as soon as possible. In either 
case, subjects will be given the contact information for the research office in case they have further 
concerns regarding their participation in the trial.   
 
Unscheduled Visits  
Patients who require evaluation outside of the three month windows +/- two weeks due to a 
related adverse event will be evaluated by the research team at the earliest convenience. If the nature 
of the evaluation is in regards to an adverse event/significant adverse event, a severe cutaneous 
reaction to the laser, or having an unrelated cosmetic procedure involving the study scar during the 
study, staff will evaluate the patient accordingly, document the event, and report any serious adverse 
events to the SLU IRB within a 24 hour window.   
Completion of Study  
At the completion of the study, the data obtained will be reviewed and analyzed with the aid of 
the Saint Louis University Center for Health Outcomes Research. This data will then be presented in the 
form of a paper and/or scientific poster. At the completion of the study, the data obtained will be 
presented in the form of a scientific paper and/or scientific poster.   
Methods of Assigning Subjects to Treatment Arms 
In terms of randomization, a spreadsheet will be created by the principle investigator with the 
aid of the research staff to predesignate the treatment assignment. For each patient that comes in, the 
principle investigator will use that as a guide to dictate the treatment arm assigned for that subject.  
Blinding  
Other than the investigating physician performing the laser treatment, no one (including the 
subjects, study coordinators, and the physicians who will be evaluating the response to treatment) will 
know who is receiving the high energy treatment or the low energy treatment until Visit #3.  
Unblinding  

14 
 
At the Visit #3, subjects and the investigating physician performing the treatments will know the 
type of treatment that the subject in question received.  
 
 
Concomitant Treatments 
Prohibited  
Patients will be prohibited from obtaining any additional cosmetic procedures during the study 
(i.e. dermabrasion, chemical peels) that may interfere with the interpretation of the results of the study.  
Permitted  
Patients will be permitted to continue using the moisturizers and cleansers that they have been 
using for the last 6 months. Patients will be allowed to take all oral medication (except isotretinoin) 
throughout the study.   
Benefits and Alternatives  
Benefits 
Participants will not receive compensation for their time or travel. They may not receive 
benefits related to the treatments either, however society may benefit from the findings derived from 
this study. The investigational product, study-related procedures and study visits that are not otherwise 
part of the standard of care for this condition will be provided at no charge to the subject or to the 
subject’s insurance company.   
 
Alternatives 
Participants may receive standard of care treatments (corticosteroids injections, ablative laser, 
non-ablative laser, and dermabrasion) in lieu of being a part of this study. A participant's choice of 
whether or not to participate will not affect their clinical care. 
Fractional ablative laser resurfacing may be superior to the other currently available treatments. 
Treatment with corticosteroid injections alone has known side effects of atrophy, striae development, 
injection site-related reactions that are not caused by ablative laser treatment. The literature 
demonstrates that non-ablative laser therapy is not potent enough to generate the changes necessary 
to alter the dimensions and features of the scar. Microdermabrasion removes the strateum corneum 
and superficial spinous layer, which are not the layers where the collagen remodeling is active in the 
scar formation. It also has mixed results in improving scars. Manual dermasanding is labor intensive and 
the results from motorized dermabrasion are operator-dependent. Additionally, only particular scars 
(i.e. fibrotic scars, ice pick scars, scars with significant tissue loss) are most amenable to this motorized 
dermabrasion. Additionally, dermabrasion involves aerosolized particle formation, which may or may 
not be infectious. 
Safety 

15 
 
 
The safety of subjects will be maintained. Subjects will be provided with information 
about the risks associated with laser therapy, severity, and time course for resolution will be addressed 
during the consent process. Such risks include the following: infection (days, mild, reversed with topical 
antivirals),  pinpoint bleeding (occasionally occurs, resolves with application of pressure dressing),  
scarring (uncommon, varies, may be ameliorated with different laser settings), erythema (very common, 
severity varies, resolves over a few days to months with sun avoidance and sunscreen use), 
postinflammatory hyperpigmentation (occasionally occurs, varies, reverses with sunscreen use), and 
delayed-onset hypopigmentation (occasionally occurs, varies, self-resolves with sunscreen use), 
bronzing (common, varies, reverses with daily sunscreen use and time), exposure to laser smoke, visible 
skin patterns, damaged skin, distortion of anatomic features, acute pain, crusting (very common, 
severity varies, resolves over days),  pruritus (common, varies, ameliorated with neutralizing moisturizer 
and self-resolves), edema (common, varies, self-resolves days to weeks) xerosis (commonly occurs, mild-
to-moderate, reverses with neutralizing moisturizer cream), allergic reactions, delayed healing, surgical 
anesthesia, additional treatment or surgery may be necessary.  
 
Topical and/or local medication used to numb the treatment area prior to the laser treatment 
may be offered. Adverse reactions associated with use of topical lidocaine cream and injectable 
lidocaine include skin rash, redness, itching, hives, burning, stinging, swelling, tenderness, and transient 
(temporary) loss of skin color, lightheadedness, anxiety, dizziness, vomiting, local erythema, local 
edema, abnormal sensations, hypersensitivity reactions, anaphylactoid reactions, central nervous 
system excitation or depression, cardiac arrest, irregular heart rhythms, and familial malignant 
hyperthermia exacerbation. The adverse reactions are anticipated to occur rarely due to the small doses 
required for laser treatment pain control. Some anesthetic agents contain epinephrine, which may 
cause short-term moderate anxiety, fear or an uneasy feeling, restlessness, shaking, weakness, dizziness, 
sweating, rapid or abnormal heart beats, increased blood pressure, pale skin, nausea and vomiting, 
headache, and/or difficulty breathing.  These symptoms are more likely in people with high blood 
pressure or an overactive thyroid.  Excessive doses of epinephrine may cause severe high blood 
pressure, stroke, and irregular heartbeats, which can lead to death. 
 
Adverse reactions associated with acyclovir include nausea, vomiting, diarrhea, headache, 
malaise, dizziness, arthralgia, rash, seizures, hallucinations, psychosis, anaphylaxis, angioedema, renal 
failure, and blood dyscrasias. The adverse reactions are anticipated to occur rarely due to the low dose 
short term prophylactic dose. During the treatment, subjects will be provided with eye protection during 
the treatment.  Additionally, subjects will be provided with the contact information of the principle 
investigator, the research team, and IRB office should they experience any unforeseen adverse effects 
or develop questions regarding the severity of the adverse effects they experience.  
 
Early Study Termination 
There are no guidelines or endpoints by which early decisions regarding efficacy or lack of 
efficacy will be made for this FDA approved device. However, the PI could stop the study early if 
significant unexpected adverse events occur, or enrollment and retention is not adequate.   
Definition of Adverse Events 
 
An adverse event is any untoward medical occurrence associated with the use of a study drug in 
humans, whether or not considered device related. An AE can, therefore, be any unfavorable and 

16 
 
unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated 
with the use of the study device, whether or not related to the study device.  
Reporting of Adverse Events  
Only AEs that occur during or following study treatment with the drug will be reported in the AE 
section of the source documents. Events recorded prior to study treatment with the drug will be 
reported in the Medical History section of the source documents as appropriate. All AEs occurring during 
the course of the study will be individually recorded in the source documents. A condition that is 
present prior to administration of study drug and that worsens after administration of study drug should 
be reported as an AE. Information regarding the onset, duration, severity, action taken, outcome, 
and relationship to study drug will be recorded. New or worsening abnormal laboratory values and/or 
vital signs are to be recorded as AEs if they are considered to be of clinical significance by the PI or meet 
the criteria of an SAE (see below). Unless a diagnosis is available, signs and symptoms must be reported 
as individual AEs in the source documents; a diagnosis is preferred. 
 
Adverse events (AEs) will be monitored throughout the study. Subjects will be instructed to 
inform the Principal Investigator (PI) and/or study staff of any AEs. At each visit, subjects will 
be asked about AEs in a non-specific manner using open-ended questions so as not to bias the 
response (e.g., Has the subject had any changes since the last visit?). Specific inquiry regarding reported 
AEs will be conducted when applicable. All adverse events will be documented and recorded in the 
source documents. 
 
Any subject who has an AE (whether serious or non-serious) or clinically significant abnormal 
laboratory test value will be evaluated by the PI and will be treated and/or followed up until the 
symptoms or values return to normal or to clinically acceptable levels, as judged by the PI. A 
physician, either at clinical site, or at a nearby hospital emergency room, will administer 
treatment for any serious adverse events (SAEs), if necessary. When appropriate, medical tests 
and examinations will be performed to document resolution of event(s). 
 
Intensity Grading of AEs  
The severity of an AE will be designated as mild, moderate or severe. The term “severe” is used 
to describe the intensity of an adverse event; the event itself, however, may be of relatively 
minor clinical significance (e.g. ‘severe’ upper respiratory infection). Severity is not the same as 
“serious”. Seriousness of AEs is based on the outcome/action of an AE. 
 
 
  
 
 
Causality and Relatedness  
The relationship of the AE to the study treatment will be based on the following two definitions: 
 
Not related: An AE is defined as “not related” if the AE is not judged to be associated with the 
study treatment and is attributable to another cause; 
 
Related: An AE is defined as “related” where a causal relationship between the event and the 
study treatment  is a reasonable possibility (possibly or probably related). A reasonable causal 
relationship is meant to convey that there are facts (e.g., evidence such as dechallenge/ 
rechallenge) or other clinical arguments to suggest a causal relationship between the AE and 
study treatment. 
 

17 
 
Serious Adverse Events 
Definition of Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that, at any device setting or dose: 
• Results in death; 
• Is immediately life-threatening (i.e., in the opinion of the PI, the AE places the subject at 
immediate risk of death; it does not include a reaction that, had it occurred in a more 
severe form, might have caused death); 
• Requires inpatient hospitalization or results in prolongation of an existing hospitalization; 
• Results in persistent or significant disability or incapacity; 
• Is a congenital anomaly or birth defect; 
• Is an important medical event that may not be immediately life-threatening, results in 
death, or require hospitalization, but may be considered an SAE when, based upon 
appropriate medical judgment, it jeopardizes the subject or may require medical or 
surgical intervention to prevent one of the outcomes listed above. 
 
Reporting Serious Adverse Events  
As soon as the PI becomes aware of an AE that meets the criteria for an SAE, the SAE should be 
documented to the extent that information is available. A report must be submitted by the study 
site to the SLU IRB, within 24 hours. Forms for reporting SAEs will be provided to the study site. 
SAEs will be recorded from the time of informed consent, through the end of the study. If in the 
opinion of the Investigator, an SAE occurring outside the specified time window (i.e., following 
subject completion or withdrawal from the study), is deemed to be device related, then the event 
should be reported with 24 hours as outlined above. The Investigator should institute any clinically 
necessary supplementary investigation of SAE information.  
 
 
Death  
In the case of subject death, any post-mortem findings/reports will be requested and a report (even if a 
preliminary diagnosis/cause of death is available) will be submitted to the SLU IRB within 24 hours of 
learning about the death. 
Reporting of Pregnancy 
In the case of subject pregnancy, the subjects will be discontinued from the study and will be followed 
leading up to delivery. 
Data Analysis and Statistical Considerations  
At the completion of the study, the data obtained will be reviewed and analyzed with the aid of the 
Saint Louis University Center for Health Outcomes Research. A chi-square test along with the Wilcoxon 
signed rank test will be performed to assess significant difference between clinical improvement scores 
between study visits. There is no data to suggest that there is a difference in the appearance of older 
(more than 1 year old from the initial injury) and newer scars post-therapy. We will aim to recruit 20 
patients with old scars (10 of which will be in the high energy treatment group, and 10 of which will be 
in the low energy treatment group). In terms of statistical analysis, we will review whether there is a 
difference between the post-treatment measurements and appearance of older scars and newer scars.    

18 
 
 
 
 
Quality Control and Quality Assurance  
Quality control and assurance for this study will be performed by an internal review every 3 
months to ensure that the data collected is in accordance with the goals of this study and to address any 
issues with data collection or performance of any study procedures.  
Direct Access, Data Handling and Record Keeping  
Access to all study materials will be kept in a locked facility within the SLU Dermatology Des 
Peres Office. Only staff members will have access to this room. With respect to the randomization 
spreadsheet, only the principle investigator will have access to this information. This information will be 
kept in a locked file cabinet in her office.  The source documents created by the study site will be the 
primary forum for recording study data.  When the study is completed, these documents will be placed 
in a long term storage facility owned by SLU.  
Confidentiality 
Interested subjects will sign a HIPPA form allowing access to relevant medical records. All study 
data will remain confidential, unless it is deemed by the principle investigator and/or research team 
members that it is important for the patient’s health for study participation to be disclosed to 
appropriate parties (i.e. other medical providers). Study materials for each subject will have a 
deidentified code, such as subject Jane Doe is subject 001. 
Data Protection 
The master list, which will be password-protected, will be kept confidential to all research staff 
except the principle investigator. She will be the only unblinded individual in this study who will set the 
password for this document and will have access to the master list. Study materials for each subject will 
have a deidentified code, such as subject Jane Doe is subject 001. 
Records Retention 
  
Records will be retained within a locked office within the SLU Dermatology Des Peres Office 
 Posting to Clinical Trials Register and Publication 
Information about this study will be posted to the Clinical Trials Register (accessible via 
http://www.clinicaltrials.gov). Recruitment for the study will be open until the study has obtained 50 
patients. All recruitment information posted to the Clinical Trials Register will be reviewed and approved 
by the SLU IRB. Final data analysis and publication will be between July and August 2017. 
 
 
 

19 
 
 
 
 
References  
1. Bodendorf MO, Grunewald S, Wetzig T, Simon JC, Paasch U. Fractional laser skin therapy. J Dtsch 
Dermatol Ges. 2009 Apr;7(4):301-8. doi: 10.1111/j.1610-0387.2008.06845.x. Epub 2008 Aug 28. Review. 
English, German.PubMed PMID: 18761608. 
 
2. Chapas AM, Brightman L, Sukal S, Hale E, Daniel D, Bernstein LJ, Geronemus RG.Successful treatment 
of acneiform scarring with CO2 ablative fractional resurfacing. Lasers Surg Med. 2008 Aug;40(6):381-6. 
doi: 10.1002/lsm.20659. PubMed PMID: 18649382. 
 
3. Majid I, Imran S. Fractional CO2 Laser Resurfacing as Monotherapy in the Treatment of Atrophic Facial 
Acne Scars. J Cutan Aesthet Surg. 2014 Apr;7(2):87-92. doi: 10.4103/0974-2077.138326. PubMed PMID: 
25136208; PubMed Central PMCID: PMC4134658. 
 
4. Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photothermolysis: a new concept 
for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med. 
2004;34(5):426-38. PubMed PMID:15216537. 
 
5: Omi T, Numano K. The Role of the CO2 Laser and Fractional CO2 Laser in Dermatology. Laser Ther. 
2014 Mar 27;23(1):49-60. doi: 10.5978/islsm.14-RE-01.Review. PubMed PMID: 24771971; PubMed 
Central PMCID: PMC3999431. 
 
6. van der Wal MB, Tuinebreijer WE, Bloemen MC, Verhaegen PD, Middelkoop E, vanZuijlen PP. Rasch 
analysis of the Patient and Observer Scar Assessment Scale(POSAS) in burn scars. Qual Life Res. 2012 
Feb;21(1):13-23. doi:10.1007/s11136-011-9924-5. Epub 2011 May 20. PubMed PMID: 21598065; 
PubMed Central PMCID: PMC3254877.