Simultaneous Versus Sequential Fractional CO2 Laser and Subcision Combination for Post-acne Atrophic Scars: A Split-face Comparative Study.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Change from baseline skin thickness at 3 months after the last treatment session.
Study Overview
Brief Summary
Acne vulgaris, a disease of the pilosebaceous unit, is estimated to afflict 9.4% of the global population, making it the eighth most prevalent and third most significant disease according to the global burden of disease. Post-acne atrophic scars may develop in 95% of acne patients due to aberrant wound healing that affects the pilosebaceous unit and surrounding tissue. Scars are cosmetically unattractive, contributing to the severe psychosocial discomfort observed in acne vulgaris patients.
Several approaches exist for the treatment of post-acne atrophic scars, depending on various factors such as the individual's condition, the types of scars present, and the associated expenses. However, treating atrophic acne scars remains challenging for physicians because there is no gold-standard treatment. Thus, combinations of interventions are typically necessary.
Fractional CO2 laser and subcision are therapeutic methods proven to be effective in treating post-acne atrophic scars. By creating hundreds of thousands of micro-heat treatment zones (MTZs), fractional CO2 lasers emitting small focal spots (50-80 m) via high-focusing mirrors can efficiently treat acne scars. These thermal damage columns accelerate the healing process of collagen synthesis. Subcision, which can be safely paired with other operations, should be the initial step in treating acne scars since it separates scars from underlying structures. Although several studies proposed that the combination of fractional CO2 laser and subcision was more efficacious than a single therapeutic modality, no study has to date compared the efficacy and safety of simultaneous versus sequential combination of these two methods in the treatment of post-acne atrophic scars. There is a critical need for basic research on the effectiveness and adverse events of combining modalities sequentially as compared to simultaneously due to the high expense of traveling and the downtime needed to recover after each treatment, especially for diseases requiring long-term and periodic intervention such as post-acne atrophic scars.
Wound healing is a dynamic process with four distinct but overlapping phases: hemostasis, inflammation, proliferation, and remodeling. The proliferation phase, during which new tissue is formed by a matrix of collagen, elastin, glycosaminoglycans, and other fibrous proteins, begins about four to twenty-one days following an injury. If sequential modalities interfere with each other's proliferative processes, therapeutic efficacy may be compromised. Therefore, our working hypothesis that simultaneous combination is more effective than sequential combination is based on the fact that if the wound-healing process is interrupted, it may stop or progress inadequately. In addition, the investigators anticipate no significant difference between these methods in terms of adverse events frequency and severity, but the downtime in the sequential combination group might be greater than that of the simultaneous combination group. The investigators propose to test the hypothesis by addressing the following two specific aims:
Aim 1: to compare the efficacy and patient satisfaction of simultaneous versus sequential treatment using fractional CO2 laser plus subcision.
Aim 2: To compare adverse reactions of simultaneous and sequential treatment using fractional CO2 laser plus subcision.
Upon completion of this study, the investigators will have (a) compared the treatment outcome of simultaneously versus sequentially combined fractional CO2 laser plus subcision based on ECCA clinical grading score, patient satisfaction, and skin thickness via high-frequency ultrasonography; and (b) compared the incidence and duration of adverse events in simultaneous versus sequential treatment. Optimizing the combination of different interventions will contribute to more efficacious and economical treatment protocols for post-acne atrophic scars.
Detailed Description
BACKGROUND
Acne vulgaris and post-acne atrophic scar:
Acne vulgaris, a highly prevalent, multifactorial disorder of the pilosebaceous unit, is characterized by symptomatic discomfort, scarring, emotional and psychological suffering, occupational implications, and the potential for psychiatric disorders, such as depression and suicide. According to the Global Burden of Disease Project, acne has a prevalence of 9.4%, making it the third most significant and the eighth most widespread disease globally.
Post-acne scarring is a permanent, significant consequence of acne vulgaris, affecting 90 to 95 percent of acne patients regardless of severity, with 30 percent suffering from severe scarring. Atrophic scarring is frequently unsatisfactory from an aesthetic standpoint, contributing to the severe emotional distress reported in acne vulgaris patients. One of the primary driving factors for individuals seeking acne treatment is the concern about scarring.
Severity assessment of post-acne atrophic scars is fundamental for patient counseling, appropriate treatment methods selection, treatment efficacy evaluation, and scientific study. Current severity assessment methods of post-acne atrophic scarring involve clinical grading scales such as the ECCA score (echelle d'evaluation clinique des cicatrices d'acne) and objective imaging techniques such as high-frequency ultrasonography.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with post-acne atrophic scars on both facial sides visiting HCMC Hospital of Venereology and Dermatology in the conducting period;
- •Agreement to give written informed consent and authorization for release of personal health data.
Exclusion Criteria
- •Patients in pregnancy or lactation
- •Patients who use oral isotretinoin within the preceding six months or topical retinoids (tretinoin, retinol, tazoretin, tazarotene) within the preceding two weeks
- •Patients with active moderate-severe acne vulgaris
- •Patients with a history of keloid/hypertrophic scar formation
- •Patients undergone cosmetic procedure (filler injections, botulinum toxin A, ablative/non-ablative laser resurfacing procedures, chemical reconstruction of skin scars, collagen induction therapy using a microneedle therapy system at the treatment site within the preceding six months
- •Patients undergoing immunosuppressive therapy
- •Patients currently using anticoagulative or antiplatelet medications
- •Patients with active infections at the treatment sites; (i) patients with systemic diseases (heart failure, diabetes,...)
- •Patients with active Herpes simplex infections at the treatment sites.
Arms & Interventions
Left face
The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision
Intervention: Simultaneous combination of fractional CO2 laser and subcision (Procedure)
Left face
The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision
Intervention: Fractional CO2 laser (Device)
Left face
The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision
Intervention: Subcision (Procedure)
Left face
The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision
Intervention: Lidocaine/Prilocaine 2.5%-2.5% Topical Application Cream (Drug)
Left face
The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision
Intervention: Paracetamol (Drug)
Left face
The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision
Intervention: Lidocaine 2% Injectable Solution (Drug)
Right face
The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.
Intervention: Sequential combination of fractional CO2 laser and subcision (Procedure)
Right face
The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.
Intervention: Lidocaine/Prilocaine 2.5%-2.5% Topical Application Cream (Drug)
Right face
The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.
Intervention: Fractional CO2 laser (Device)
Right face
The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.
Intervention: Subcision (Procedure)
Right face
The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.
Intervention: Paracetamol (Drug)
Right face
The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.
Intervention: Lidocaine 2% Injectable Solution (Drug)
Outcomes
Primary Outcomes
Change from baseline skin thickness at 3 months after the last treatment session.
Time Frame: Change from baseline and 3 months after the last treatment session
Before the treatment and three months after the final session, a high-frequency ultrasound system (Supersonic Mach 30, Hologic, SuperSonic Imagine, Aix-en-Provence, France), which uses a 20 MHz linear probe with 8mm penetration, 30x12m um resolution, provides a quantitative assessment and measurements in mm. Acquired HFUS images are imported into MATLAB's image segmenter to segment and delineate skin layers. A MATLAB code is applied to assess skin thickness from segmented images. The skin's overall thickness, epidermis, and dermis at the treatment sites are also measured (unit: mm).
Change from baseline skin thickness at 6 months after the last treatment session.
Time Frame: Change from baseline and 6 months after the last treatment session
Before the treatment and six months after the final session, a high-frequency ultrasound system (Supersonic Mach 30, Hologic, SuperSonic Imagine, Aix-en-Provence, France), which uses a 20 MHz linear probe with 8mm penetration, 30x12m um resolution, provides a quantitative assessment and measurements in mm. Acquired HFUS images are imported into MATLAB's image segmenter to segment and delineate skin layers. A MATLAB code is applied to assess skin thickness from segmented images. The skin's overall thickness, epidermis, and dermis at the treatment sites are also measured (unit: mm).
ECCA score at 3 months after the last treatment session.
Time Frame: 3 months after the last treatment session.
The ECCA score (echelle d'evaluation clinique des cicatrices d'acne) provides a quantitative grading score for evaluating scars' severity and clinical improvement, with a minimum - maximum value is 0 - 540. A higher score means higher severity of acne scars condition.
Patient's Global Assessment at Week 8
Time Frame: 8 weeks after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by patients is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
ECCA score at week 4
Time Frame: Week 4
The ECCA score (echelle d'evaluation clinique des cicatrices d'acne) provides a quantitative grading score for evaluating scars' severity and clinical improvement, with a minimum - maximum value is 0 - 540. A higher score means higher severity of acne scars condition.
ECCA score at week 8
Time Frame: Week 8
The ECCA score (echelle d'evaluation clinique des cicatrices d'acne) provides a quantitative grading score for evaluating scars' severity and clinical improvement, with a minimum - maximum value is 0 - 540. A higher score means higher severity of acne scars condition.
Investigator's Global Assessment at Week 8
Time Frame: 8 weeks after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by a blinded investigator is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Investigator's Global Assessment at Week 12
Time Frame: 12 weeks after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by a blinded investigator is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Investigator's Global Assessment at 3 months
Time Frame: 3 months after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by a blinded investigator is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
ECCA score at Week 12
Time Frame: Week 12
The ECCA score (echelle d'evaluation clinique des cicatrices d'acne) provides a quantitative grading score for evaluating scars' severity and clinical improvement, with a minimum - maximum value is 0 - 540. A higher score means higher severity of acne scars condition.
ECCA score at 6 months after the last treatment session.
Time Frame: 6 months after the last treatment session.
The ECCA score (echelle d'evaluation clinique des cicatrices d'acne) provides a quantitative grading score for evaluating scars' severity and clinical improvement, with a minimum - maximum value is 0 - 540. A higher score means higher severity of acne scars condition.
Investigator's Global Assessment at Week 4
Time Frame: 4 weeks after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by a blinded investigator is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Patient's Global Assessment at Week 4
Time Frame: 4 weeks after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by patients is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Patient's Global Assessment at 3 months
Time Frame: 3 months after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by patients is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Patient's Global Assessment at 6 months
Time Frame: 6 months after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by patients is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
ECCA score at baseline
Time Frame: Baseline
The ECCA score (echelle d'evaluation clinique des cicatrices d'acne) provides a quantitative grading score for evaluating scars' severity and clinical improvement, with a minimum - maximum value is 0 - 540. A higher score means higher severity of acne scars condition.
Patient's Global Assessment at Week 12
Time Frame: 12 weeks after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by patients is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Investigator's Global Assessment at 6 months
Time Frame: 6 months after the last treatment session.
Photographs (five photos taken at 0,45 and 90 degrees of each half face, and multiple close-ups at the scar sites) are taken at baseline, before each treatment session, and three months after the last session. When comparing images taken prior to and after therapy, the head's position, distance from the camera, and illumination remain constant. Evaluation of global assessment to treatment by a blinded investigator is done using patient photographs of before and after treatment. Rating the Investigator's Global Response to treatment is done using a quartile grading scale (0 = no improvement 0%; 1 = mild improvement 1% - 25%;2 = moderate improvement 25%-49%; 3 = significant improvement 50%-74%; 4= marked improvement ≥ 75%).
Patients Satisfaction
Time Frame: 6 months after the last treatment session.
Patients are asked to rate their satisfaction with each type of combination therapy on a four-point Likert scale with the following anchors: extremely satisfied, satisfied, partially satisfied, and dissatisfied.
Secondary Outcomes
- Edema(Week 12)
- Crusting(Week 12)
- Pain level after laser(Week 8 (right after third treatment session))
- Bruising(Week 12)
- Downtime(Week 12)
- Pain level after subcision(Week 8 (right after third treatment session))
- Other adverse events(Week 12)
- Erythema(Week 12)
- Lump(3 months after last treatment session)