Simultaneous Versus Sequential Fractional CO2 Laser and Subcision Combination for Post-acne Atrophic Scars: A Split-face Comparative Study.

NCT05688202 | Completed

• 1 other identifier: CS/BVDL/22/16
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrophic Acne Scar

Keywords

Simultaneous; Sequential; Fractional CO2 Laser; Subcision; Combination; Treatment; Split-face; Comparative Study

Outcome Measures

Primary Outcomes (19)

• Change from baseline skin thickness at 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 and 3 months after the last treatment session

• Change from baseline skin thickness at 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).

  Change from baseline and 6 months after the last treatment session

• ECCA score at 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.

  Baseline

• ECCA score at 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.

  Week 4

• ECCA score at 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.

  Week 8

• ECCA score at 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.

  Week 12

• ECCA score at 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.

  3 months after the last treatment session.

• ECCA score at 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.

  6 months after the last treatment session.

• Investigator's Global Assessment at Week 4

  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%).

  4 weeks after the last treatment session.

• Investigator's Global Assessment at Week 8

  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%).

  8 weeks after the last treatment session.

• Investigator's Global Assessment at Week 12

  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%).

  12 weeks after the last treatment session.

• Investigator's Global Assessment at 3 months

  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%).

  3 months after the last treatment session.

• Investigator's Global Assessment at 6 months

  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%).

  6 months after the last treatment session.

• Patient's Global Assessment at Week 4

  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%).

  4 weeks after the last treatment session.

• Patient's Global Assessment at Week 8

  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%).

  8 weeks after the last treatment session.

• Patient's Global Assessment at Week 12

  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%).

  12 weeks after the last treatment session.

• Patient's Global Assessment at 3 months

  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%).

  3 months after the last treatment session.

• Patient's Global Assessment at 6 months

  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%).

  6 months after the last treatment session.

• Patients Satisfaction

  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.

  6 months after the last treatment session.

Secondary Outcomes (25)

• Pain level after laser

  Baseline (right after first treatment session)

• Pain level after laser

  Week 4 (right after second treatment session)

• Pain level after laser

  Week 8 (right after third treatment session)

• Pain level after subcision

  Baseline (right after first treatment session)

• Pain level after subcision

  Week 4 (right after second treatment session)

Study Arms (2)

Left face

ACTIVE COMPARATOR

The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision

Procedure: Simultaneous combination of fractional CO2 laser and subcision; Device: Fractional CO2 laser; Procedure: Subcision; Drug: Lidocaine/Prilocaine 2.5%-2.5% Topical Application Cream; Drug: Paracetamol; Drug: Lidocaine 2% Injectable Solution

Right face

PLACEBO COMPARATOR

The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.

Procedure: Sequential combination of fractional CO2 laser and subcision; Device: Fractional CO2 laser; Procedure: Subcision; Drug: Lidocaine/Prilocaine 2.5%-2.5% Topical Application Cream; Drug: Paracetamol; Drug: Lidocaine 2% Injectable Solution

Interventions

Simultaneous combination of fractional CO2 laser and subcision PROCEDURE

Fractional CO2 laser is performed immediately following subcision. Subcision is operated in all participants using an 181/2G Nokor needle (BD Nokor™ Admix Needles, United States). The insertion depth is at the dermal-hypodermal junction. The subcision needle is advanced and retracted in a tunneling motion to penetrate the fibrotic scar tissue, then slid in a direction parallel to the skin's surface in order to detach the scar from its tethers. All participants undergo FrCO2 laser (10 600-nm eCO2 laser, Lutronic Corporation, Goyang, Korea) with the parameters following the suggested regimen at static mode: 120 μm beam size, 30 W peak power, 30 - 120 mJ pulse energy, 50-75 spots/cm2 density, with two passes: (1)Only the atrophic scars are treated using a 4mm square or circle pattern, 100-120 mJ pulse energy, and 50 spots/cm2 density. (2)The whole half side of the face is treated using a 12mm square pattern, 30-40 mJ pulse energy, and 75 spots/cm2 density, \<10% overlap.

Left face

Sequential combination of fractional CO2 laser and subcision PROCEDURE

Fractional CO2 laser conducted two weeks after subcision. Subcision is operated in all participants using an 181/2G Nokor needle (BD Nokor™ Admix Needles, United States). The insertion depth is at the dermal-hypodermal junction. The subcision needle is advanced and retracted in a tunneling motion to penetrate the fibrotic scar tissue, then slid in a direction parallel to the skin's surface in order to detach the scar from its tethers. All participants undergo FrCO2 laser (10 600-nm eCO2 laser, Lutronic Corporation, Goyang, Korea) with the parameters following the suggested regimen at static mode: 120 μm beam size, 30 W peak power, 30 - 120 mJ pulse energy, 50-75 spots/cm2 density, with two passes: (1)Only the atrophic scars are treated using a 4mm square or circle pattern, 100-120 mJ pulse energy, and 50 spots/cm2 density. (2)The whole half side of the face is treated using a 12mm square pattern, 30-40 mJ pulse energy, and 75 spots/cm2 density, \<10% overlap.

Right face

Fractional CO2 laser DEVICE

Fractional CO2 laser (10 600-nm eCO2 laser, Lutronic Corporation, Goyang, Korea) on both sides of the face sequentially with a two-week interval between sessions for each face's side by a single physician, with the parameters following the suggested regimen at static mode: 120 μm beam size, 30 W peak power, 30 - 120 mJ pulse energy, 50-75 spots/cm2 density, with two passes. At the first pass, only the atrophic scars are treated using a 4mm square or circle pattern, 100-120 mJ pulse energy, and 50 spots/cm2 density in the static operating mode. At the second pass, the whole half side of the face is treated using a 12mm square pattern, 30-40 mJ pulse energy, and 75 spots/cm2 density in the static operating mode with less than 10% overlap.

Left face; Right face

Subcision PROCEDURE

Subcision is operated in all participants using an 1812G Nokor needle (BD Nokor™ Admix Needles, Becton, Dickinson and Company, New Jersey, United States). The operation sites are sterilized with alcohol pads and injected intradermally with a solution of 2% lidocaine. After obtaining appropriate anesthesia, a Nokor needle is inserted into the skin close to the depressed scars and progressed until it lays precisely under the scar. The insertion depth is at the dermal-hypodermal junction. Initially, the subcision needle is advanced and retracted in a tunneling motion to penetrate the fibrotic scar tissue. Once the fibrous mass has been sufficiently fractured, the needle is slid in a direction parallel to the skin's surface in order to detach the scar from its tethers. For densely fibrous scars, several needle insertion sites are used to undermine the defect from various angles.

Left face; Right face

Lidocaine/Prilocaine 2.5%-2.5% Topical Application Cream DRUG

Preoperative, lidocaine 2.5% and prilocaine 2.5% cream (EMLA 5%, eutectic mixture of local anesthetic; AstraZeneca LP, Wilmington, DE, USA) is applied under occlusion for 60 minutes prior to the removal of local anesthetics

Left face; Right face

Paracetamol DRUG

A 500 mg paracetamol-based oral analgesic (Efferalgan, Upsa SAS, France) is administered right before the procedure.

Also known as: Acetaminophen

Left face; Right face

Lidocaine 2% Injectable Solution DRUG

The operation sites are sterilized with alcohol pads and injected intradermally with a solution of 2% lidocaine.

Left face; Right face

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ho Chi Minh City Hospital of Dermato-Venereology: lead

Study Sites (1)

Ho Chi Minh City Hospital of Dermato - Venereology

Ho Chi Minh City, 700000, Vietnam

Location

MeSH Terms

Interventions

Lidocaine; Prilocaine; Acetaminophen

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Quoc Bao Tran, Doctor

  Ho Chi Minh City Hospital of Dermato-Venereology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Each patient will undergo three sessions of subcision combined with fractional CO2 laser with a 1-month interval between sessions. The face's left side is treated with simultaneous combination therapy, in which fractional CO2 laser is performed immediately following subcision. The face's right side receives sequential combination therapy with fractional CO2 laser conducted two weeks after subcision.

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 18, 2023
• Study Start: October 24, 2022
• Primary Completion: September 12, 2023
• Study Completion: September 12, 2023
• Last Updated: October 4, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Starting 6 months after publication
• Access Criteria: Information of request reviewer: Name: QUOC BAO TRAN Phone number: (+84) 934181096 Email: baotran181019996@gmail.com Address: 02 Nguyen Thong, Ward Vo Thi Sau, District 3, Ho Chi Minh City, Vietnam

Locations

VN (1)