a study to Compare the efficacy of combination of Fractional CO2 laser with Intralesional Steroid injection against Intralesional Steroid injection alone in the treatment of keloids and hypertrophic scars
- Conditions
- Acne keloid, (2) ICD-10 Condition: L910||Hypertrophic scar,
- Registration Number
- CTRI/2023/01/048755
- Lead Sponsor
- Lady Hardinge Medical College and Shrimati Sucheta Kriplani Hospital, New Delhi
- Brief Summary
Keloids and hypertrophic scars (HTS) are abnormal fibrous reactions to trauma, inflammation, surgery or burns. They frequently occur in the age group of 10-30 years. Hypertrophic scarring is related to a prolonged inflammatory phase followed by pathological modifications of wound healing process such as hypercellularity, augmented neovascularization and excessive collagen production.HTS and keloids may continue to grow for months or years.
Keloids are distinguished from HTS by their extension beyond the original sites of trauma, persistence for a prolonged period, rare resolution without treatment, and recurrence after excision. HTS have low recurrence rates.
The incidence of hypertrophic scars varies from 30% to 50% after surgery or trauma. Areas of highest skin tension like the upper back, shoulders, anterior chest, and upper arms are commonly affected. Although hypertrophic scars tend to improve over time; patients may suffer from severe physical symptoms like pruritis (73%), pain (68%), pressure, reduced range of motion, and psychological symptoms due to the cosmetic aspect (75%). Thus, treatment of HTS and keloid is of utmost importance.
Therapeutic approaches fall into three broad categories: alteration of the inflammatory response, modification of collagen metabolism, and surgical and physical manipulation of the shape of the scar. Silicone products may influence hypertrophic scarring by enabling constant hydration of the scar tissue as a consequence of the applied silicone membrane. Application of mechanical pressure to the scar surface via pressure garments decreases blood and oxygen flow into the scar tissue, which may reduce cellular proliferation and prevent excessive scarring. More invasive methods such as intralesional injections of corticosteroids, chemotherapeutics, bleomycin, botox, and other substances interfere in the process of pathological scarring. Additionally, there exist many physical therapy options with the intent to break down and/or remodel excessive scar tissue. Cryotherapy, radiotherapy, and lasers are currently the most commonly used approaches. Surgical excision often remains the last treatment option for hypertrophic scarring and keloids, due to high chances of recurrence.1
Intralesional injection of triamcinolone acetonide (TAC) alone or combined with other modalities is the standard treatment for keloids and HTS. It decreases the synthesis of collagen, increases the collagen degradation and reduces inflammation. According to literature review, the response to intralesional corticosteroid injection (ILS) alone is variable with 50–100% regression and a recurrence rate of 33% and 50% after 1 and 5 years, respectively is seen.3Darzi MA et al in their study treated keloids and HTS with TAC and after a follow up 10yrs, they concluded that TAC produced a symptomatic relief in 72 % and complete flattening in 64 % of the lesions.
However every treatment has shortcomings. The outcome with ILS has been associated with multiple adverse effects in up to 63% of patients. It may lead to pain, skin atrophy, telangiectasias, depigmentation and secondary infections. It may also lead to plasma cortisol levels suppression when given for longer durations at higher doses. Cushing syndrome may also occur. Such major adverse effectsare associated with a high cumulative dose of TAC in adults, whereas in children they may even occur after a single treatment with 40 mg of TAC. Thus, it must be administered carefully in children and patients with multiple or very large lesions.
To reduce the chances of side effects, the amount injected normally ranges from 0.1 to 0.5 mL of 40mg/mL solution, depending on the size and nature of the lesion. No more than 30 mg of TAC should be given in one session, with a maximum of 5 mg at any one site.
Fractional CO2 laser (FCL) is a favourable mode of treatment in all skin types and has potential use in HTS and keloids. It is based on the fundamental principle of photothermolysis. FCL with a wavelength of 10,600 nm acts on fibroblasts in vitro by stimulating basic fibroblast growth factor (bFGF) and inhibiting transforming growth factor β1 (TGF β1), which leads to normalized wound healing.
In a Meta analysis of 8 studies conducted on the use of ablative CO2 laser in hypertrophic burn scars by Mahar P et al, it was concluded that when compared to pre-treatment values, the improvement of scars in the included studies, as measured by the Vancouver Scar Scale (VSS), varied from 14% to 79%.
Despite being safe, there are certain adverse effects associated with FCL like hyperpigmentation, hypopigmentation, reactivation of a herpes simplex cold sore, bacterial infections, postoperative swelling, bleeding diathesis etc.
While individual therapies are effective, combined therapeutic approaches have proved to be more effective since they act at different stages of the inflammatory pathway. A combined therapy of FCL+ILS gives better scar results in terms of more reduction in height, better appearance and better side effect profile. As concluded by Alexander et al, the lesions showed improvement over the sessions with a significant improvement in length and flattening in height in FCL+ILS group as against ILS only group. Among the modified Manchester Quartile Scale parameters assessed, it was found that overall appearance parameter showed an improvement of more than 50% in 43.3% of the lesions.2
**RESEARCH QUESTION**
Is Combination of Fractional CO2 laser with Intralesional Steroid more efficacious than Intralesional Steroid alone in the treatment of keloid and hypertrophic scar?
**HYPOTHESIS:**
Combination of Fractional CO2 laser with Intralesional Steroid is more efficacious than Intralesional Steroid alone in the treatment of keloid and hypertrophic scar.
**AIMS AND OBJECTIVES**
**Aim:** To study the efficacy of combination of Fractional CO2 laser with Intralesional Steroid(Group A) compared with Intralesional Steroid alone(Group B)in the treatment of keloids and hypertrophic scar.
**Primary Objective:**
- To compare the percentage reduction in length, breadth and height parameters in patients of Group A (FCL+ILS) and Group B (ILS alone).
**Secondary Objective:**
- To compare the percentage reduction in erythema and induration scores in patients of Group A (FCL+ILS) and Group B (ILS alone).
- To compare Patient Satisfaction Score in patients of Group A (FCL+ILS) and Group B (ILS alone).
- To study the adverse effects of therapy in patients of Group A (FCL+ILS) and Group B( ILS alone).
**MATERIALS AND METHODS**
**Study Design**:
Hospital based open label randomised control interventional study.
**Study Period**:
From November 2022 to March 2024.
**Study Area:**
Department of Dermatology & STD at Lady Hardinge Medical College (LHMC).
**Study Population**:
Adults of 18-55 years of age with HTS and keloid presenting to the Dermatology OPD.
**Inclusion criteria**
- Clinically diagnosed cases of keloid and HTS caused after burns/trauma/surgery.
- Age 18-55 years having single or multiple keloids/HTS.
- Size between 3-10 cm.
**Exclusion criteria**
1. Patients having keloid/HTS on face/ear lobes.
2. Pregnant or lactating females.
3. History of local/systemic treatment for keloid/HTS in the past 6 months.
4. Signs of active local infections or signs of systemic infection like fever(temp>370C)
5. History of uncontrolled diabetes, hypertension, cardiovascular disorders, bleeding dyscrasias.
6. On anticoagulant therapy.
7. Receiving ultraviolet therapy or radiotherapy at the same site.
**Study tools**
1. Consent form for ILS injection.(Annexure3)
2. Consent form for FCL therapy(Annexure 4)
3. Clinical proforma for keloid and HTS. (Annexure 5)
4. Clinical score for erythema and induration (Annexure 6)
5. Patient satisfaction score(Annexure 7)
6. Vernier callipers
7. Camera: iPhone 12
**Randomisation technique**: Variable block size randomisation (2, 4 or 6) will be done using computer generated randomisation sequence by person not involved in the study.
**Allocation concealment**: Sealed opaque envelopes containing group codes will be prepared. Envelopes will be sequentially numbered and kept in order according to their serial number. Envelope will be opened at the time of randomisation and the patient will be allocated to their respective group.
**OUTCOME VARIABLES:**
Primary outcome variables:
1. Percentage reduction in the length, breadth and height parameters of keloids and HTS at 16 weeks from baseline in Group A (FCL+ILS) and Group B (ILS alone).
Secondary outcome variables:
1. Percentage reduction in erythema and induration scores at 16 weeks from baseline in Group A (FCL+ILS) and Group B (ILS alone).
2. Proportion of patient showing patient satisfaction score of >6.
3. Proportion of patients experiencing adverse effects in Group A (FCL+ILS) and Group B (ILS alone).
**SAMPLE SIZE ASSUMPTIONS AND CALCULATION**
In this randomised control trial with a superiority study design, the sample size will be calculated using the following formula:
N= size per group
Z= the standard normal deviate for a one or two sided x
**δ****0****=**A clinically acceptable margin
S2 = Polled standard deviation of both comparison groups
α = Type 1 error
β = Type 2 error
**δ**= real difference between two treatment effect.
In a study conducted by Alexander S. et al in 2018 the improvement in height parameters was seen more in the combination (FCL+ILS) group (mean decrease=0.03mm) than the ILS alone group (mean decrease=0.006mm)
On substituting the values ,
Z 1- α=1.645
Z 1-β=0.845
**δ****0**=0.3
S= 0.5
**δ**= 0.024
Sample size in each group comes out to be 40.5~ 41
Due to the time constraint , limited patients presenting to the Dermatology OPD and a follow up of 1 month for each patient after the last therapy session, convenient sampling will be used .
Hence sample size will be taken as 60 with 30 subjects in each group.
**METHODOLOGY**
1. All cases of keloids and HTS will be diagnosed clinically.
A keloid is a benign well demarcated overgrowth of fibrotic tissue which extends beyond the original boundaries of a defect.
A hypertrophic scar is similar, but remains confined to the original defect and tends to resolve over time.6
The subjects who fulfil the inclusion and exclusion criteria shall be recruited for the study and subjected to a predesigned clinical proforma after taking written informed consent and giving patient information sheet. Patients will be randomised as per the randomisation technique and shall be allotted to group A (FCL+ ILS) or group B (ILS).
2. Investigations like complete blood count with Erythrocyte Sedimentation Rate (CBC with ESR), PT-INR, blood sugar (fasting+ post prandial), HBsAg, anti HCV ab, anti HIV ab will be done for all the patients.
3. Group A patients will be given sessions of FCL +ILS.
SESSION OF ILS: Administration of injection TAC 40mg/ml along with 1% lignocaine loaded in a syringe in a ratio of 1:1 will be done. Needle will be introduced into upper dermis at 30-45 degree angle to the lesion with bevel side down. 0.05-0.1ml at each site will be injected so as to cause blanching. It will be given segment wise sequentially with a multiple puncture technique so as to cover the entire lesion. The blanching will not be allowed to spread into normal adjacent tissue and the suspension within the syringe will be shaken frequently during injection process so that there is uniform deposition of the drug throughout the lesion. Each patient will be given a total of 4 sessions at intervals of 4 weeks each (0, 4, 8,12weeks) and a follow up visit will be done at 16 weeks.
SESSION OF FCL: After topical anesthetic cream will be applied for 45 mins, it will be wiped off and the desired area will be cleaned with povidone iodine solution. Pre procedure cooling will be done with ice cubes and laser will be used. In our study, we will be using super pulse and continuous wave enabled CO2 laser system (Acupulse from Lumenis). We will be using the Cosmetic mode of the laser. The parameters that will be most often used will range from 5 to 30 mJ of energy and 5% to 30% density for deep scan and energy of 50-80mJ and a density ranging from 40% to 60% for the superficial scan. Laser beams of various shapes will be used which will include square, hexagonal or line as per the various shapes and areas of keloids and HTS. Post procedure cooling followed by topical antibacterial cream containing fusidic acid for 1 week will be given to the patient. 3 sessions of laser at 2,6,10 wks will be given to the patient.
4. Group B patients will be given 4 sessions of intralesional TAC alone at 4 weekly intervals.
5. Photography of the lesion shall be done keeping fixed, preselected settings of the camera (iPhone 12) at baseline and before every subsequent session at 4, 8,12weeks and lastly at 16 weeks follow up session.
6. EVALUATION
SUBJECTIVE EVALUATION.
- Erythema and induration of the scar will be assessed using clinical scores graded from 0-3 by the primary investigator at 0, 8 and 16 weeks.
- All patients shall be asked to grade their satisfaction on a linear analogue scale of 1-10(1=no result, 10=best result), which will be recorded at16 weeks.
- Patients shall be instructed to report any side effects at each post procedural visit.
OBJECTIVE EVALUATION
- Length, breadth and height measurement will be done using vernier callipers at 0,8,16 weeks by the primary investigator and one independent observer.
7. At 16 weeks, final evaluation by comparing the reduction in length, breadth and height of the scars and the reduction in erythema and induration scores shall be done.
8. If at any point of time, the side effects associated with the use of ILS like pain, skin atrophy, telangiectasias, depigmentation, secondary infections, features suggestive of plasma cortisol levels suppression or Cushing syndrome or the adverse effects associated with the use of FCL like hyperpigmentation, hypopigmentation, reactivation of a herpes simplex cold sore, bacterial infections, postoperative swelling, bleeding diathesis occur, the therapy will be stopped and appropriate treatment of side effects will be done. The subject shall also be given a choice to drop out from the study.
9. END POINT OF THERAPY: Treatment shall be stopped after 4 sessions of therapy or complete flattening of the lesions, whichever is earlier.
10. END POINT OF STUDY: Study shall be concluded after the final follow up session at 16 weeks is held for each patient.
11. The entire data shall be recorded in excel sheet and will be evaluated statistically.
**ASSESSMENT OF OUTCOME:**
- **SUBJECTIVE**
**Clinical characteristics of scar****10** **:**
INDURATION
It refers to an increase in the fibrous elements in tissue commonly associated with inflammation and marked by loss of elasticity and pliability. Uncontrolled collagen synthesis can lead to excessive accumulation of collagen in these scars causing increase in induration. In our study, it will be graded using a 4-point scale (0 to 3) .
3= severe
2= moderate
1= mild
0=none
ERYTHEMA
It refers to abnormal redness of the skin or mucous membranes due to capillary congestion. Keloids can show erythema due to increased capillary capillary density at the site of inflammation. Like induration , it will also be graded using a 4 point scale(0-3).
3= bold red or brown
2= red
1= mild red
0= normal skin colour
- **OBJECTIVE**
**Vernier callipers**:
The vernier callipers work on the basic principle of alignment of measurement markings on the vernier scale and main scale. When a certain marking on the vernier scale aligns exactly to the marking on the main scale for a particular object whose dimensions are being measured, the value of the vernier scale reading is added to the main scale reading to obtain the decimal value of the reading in millimetres.
Main Scale Divisions (MSD): MSD refers to the divisions present between two successive marks on the main scale of a vernier calliper. Vernier Scale Divisions(VSD): VSD refer to the divisions present between two successive marks on the vernier scale. The vernier scale is constructed such that its divisions are spaced at a constant fraction of the fixed main scale. In other words, the 10 divisions present on the vernier scale do not exactly coincide with all the 10 main scale divisions. Least Count of the device is 1 mm.
**DATA MANAGEMENT AND STATISTICAL ANALYSIS:**
- Freely available analytical software will be used in the study analysis.
- Continuous variables will be expressed as mean +/- SD and will be analysed using t-test.
- Categorical variables will be expressed as frequencies and percentages, and will be analysed using chi square test.
- Statistical significance will be assumed at a p-value of <0.05
- Other appropriate test of significance will be applied wherever applicable.
**ETHICAL CONCERNS**:
- Approval of the study protocol will be obtained from the Thesis Review Board and Institutional Ethics Committee.
- Patient information sheet (either English or Hindi, as per patient preference) will be handed over to the patient to be read.
- The study design will be registered with the **Clinical Trial Registry of India**.
- The eligible adults will be enrolled in the study after taking informed written consent from them after explaining the study process and nature in detail in their own language.
- All efforts will be made that there is no delay in the treatment of patient due to the study process.
- The privacy and confidentiality of subjects will be maintained.
- If at any point of time, any side effect of the therapy(FCL/ILS) is encountered , appropriate treatment will be given to the patient at the earliest and the patient will be given a choice to opt out of the study.
- Subjects will be given liberty to opt out of the study at any point of time without any implications to the management at the institute.
- If any subject in the study will be diagnosed with any co-morbidity, appropriate referral and treatment will be given respectively.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Yet Recruiting
- Sex
- All
- Target Recruitment
- 60
- Clinically diagnosed cases of keloid and HTS caused after burns/trauma/surgery.
- Age 18-55 years having single or multiple keloids/HTS.
- Size between 3-10 cm.
- Patients having keloid/HTS on face/ear lobes.
- Pregnant or lactating females.
- History of local/systemic treatment for keloid/HTS in the past 6 months.
- Signs of active local infections or signs of systemic infection like fever(temp>370C) History of uncontrolled diabetes, hypertension, cardiovascular disorders, bleeding dyscrasias.
- On anticoagulant therapy.
- Receiving ultraviolet therapy or radiotherapy at the same site.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method percentage reduction in length ,breadth and height parameters of keloids and hypertrophic scars at 16 weeks from baseline in both the arms
- Secondary Outcome Measures
Name Time Method percentage reduction in erythema and induration scores, proportion of patients showing patient satisfaction score of more than 6,proportion of patients showing adverse effects at 16 weeks from baseline.
Trial Locations
- Locations (1)
Smt Sucheta Kriplani Hospital, New Delhi
🇮🇳Delhi, DELHI, India
Smt Sucheta Kriplani Hospital, New Delhi🇮🇳Delhi, DELHI, IndiaTwinkle YadavPrincipal investigator8586904081twinkle964dec@gmail.com