NCT07522788

Comparison Between Efficacy of Topical Tranexamic Acid Vs Topical Ethyl Ascorbic Acid In Treatment Of Melasma

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 128 (estimated)
• Sponsor: Hayatabad Medical Complex · Other Government
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This study is to compare the efficacy of topical tranexamic acid vs topical ethyl ascorbic acid in the treatment of melasma

Detailed description

Comparison Between the Efficacy of Topical Tranexamic Acid VS Topical Ethyl Ascorbic Acid in the Treatment of Melasma Introduction Melasma is a prevalent acquired condition marked by brownish to grayish patches of discoloration on sun-exposed areas of the face, predominantly affecting women. While the precise cause of melasma remains unclear, it is thought to be multifactorial, involving the interplay of genetic, hormonal, and environmental factors, along with other risk elements.1 According to reports the prevalence of melasma in Pakistan is 46%, which is quite high. 2 The etiology of melasma is complex, involving multiple factors such as genetics, UV exposure, pregnancy, and the use of hormonal contraceptives.3 Melasma treatment is challenging due to its unclear etiology, refractory nature, and frequent relapse. Current therapies are divided into non energy-dependent (e.g., hydroquinone, alpha arbutin, azelic Acid, retinoids, Vit C , chemical peels( glycolic acid, lactic acid, salicylic acid)and energy-dependent (e.g., lasers, intense pulsed light) categories.3,4 Topical tranexamic acid (TXA) and ascorbic acid are both effective in treating melasma, with outcomes varying by skin type and treatment combination. TXA demonstrates versatility, particularly when combined with lasers or hydroquinone, yielding significant pigmentation improvements. Ascorbic acid, especially with microneedling, shows notable efficacy in skin type III and outperforms TXA in specific cases. Both agents are valuable, with tailored approaches enhancing their effectiveness. (4-7) Muhammad Fahim et al. compared the effectiveness of intradermal tranexamic acid (TXA) and topical magnesium ascorbyl phosphate (MAP) in treating melasma. The study included 128 patients, divided into two groups of 64 each. Group A received intradermal TXA injections, while Group B used topical MAP cream. After 12 weeks, the study found that the efficacy of TXA was 54.7%, while MAP showed a higher efficacy of 78.1%. The study concluded that topical MAP is more effective than intradermal TXA for treating melasma .2 The rationale of this study is to compare the efficacy with topical TXA versus topical Ethyl Ascorbic Acid (EAA ) for Melasma in terms of reduction in MASI scores. Melasma treatment often involves trial and error due to variability in patient response and recurrence rates. While both TXA and EAA are widely used, comparative data on their efficacy and safety profiles in similar clinical scenarios is scarce. This study seeks to address this gap, providing insights to guide clinicians in choosing the most effective and patient-friendly option. Objective: To compare the efficacy of topical TXA versus topical EAA for Melasma in terms of reduction in mean MASI scores. Operational Definition: Melasma: It is defined as a skin condition characterised by brownish to greyish discoloration on skin. The Melasma Area and Severity Index2 It is a standardized tool that will be used to quantify the severity of melasma by evaluating three key factors: 1. Area of Involvement: This is graded on a scale from 0 to 6, where: * 0 indicates no involvement, * 6 represents 90-100% involvement. 2. Darkness: This is assessed on a scale from 0 to 4, where: * 0 indicates no pigmentation, * 4 represents severe pigmentation. 3. Homogeneity: This measures the uniformity of pigmentation on a scale from 0 to 4, where: * 0 represents no pigment, * 4 indicates completely homogeneous pigmentation. The face is divided into four regions with different weightages: * Forehead: 30% of the total score, * Right Malar: 30%, * Left Malar: 30%, * Chin: 10%. For each region, the MASI score will be calculated by multiplying the values of area, darkness, and homogeneity. The total MASI score will obtained by summing the contributions from all four regions, giving a score range from 0 to 48, where 48 indicates the most severe form of melasma. This will be calculated at the start of treatment , at 4 weeks, 8 weeks and 12 weeks after treatment by Consultant Dermatologist. Efficacy: It will be categorised based on reduction of mean MASI score from baseline at follow up after 12 weeks of last session from mean baseline MASI score. There will be three categories as follow: A. Poor : \<25% reduction in MASI B. Good: \>25 - 75% reduction in MASI C. Excellent: \> 75% reduction in MASI HYPOTHESIS Topical ethyl ascorbic acid will produce a greater reduction in MASI scores compared to topical tranexamic acid in patients with melasma, administered over same period of treatment. MATERIALS AND METHODS Study Design Randomized Controlled Trial (RCT) Study Duration 6 months, following ethical approval. Study Setting Department of Dermatology, Hayatabad Medical Complex, MTI, Peshawar. Sample Size Using a WHO sample size calculator with: * Power: 80% * Alpha: 0.05 * Expected efficacy in TXA group 2: 54.7% * Expected efficacy in Ascorbic acid group 2: 78.1% The sample size will be estimated at 122 patients (61 per group). Sampling Technique Non-consecutive probability Sampling SAMPLE COLLECTION Inclusion Criteria: * Adults aged 18-50 years * Clinically diagnosed Melasma * Irrespective of gender and ethnicity. Exclusion Criteria: * Pregnant or lactating women * Patients with a history of skin allergies to study medications * Use of systemic steroids or anticoagulants within the last month * Patients on other melasma treatments for at least 4 weeks prior Data Collection Procedure This study will be conducted as a randomized controlled trial over a duration of six months in the Dermatology Department of Hayatabad Medical Complex, MTI after approval from the institutional and CPSP ethics board. A total of 100 patients clinically diagnosed with melasma will be enrolled based on strict inclusion and exclusion criteria. Patients will be allocated into two groups (61 in each group) using a block randomization technique to ensure equal distribution. Demographic data, including age, gender, residence, duration of melasma, and Fitzpatrick skin type will be recorded at baseline. Group A will receive topical tranexamic acid (5% concentration), while Group B will be treated with topical ethyl ascorbic acid (2% concentration). Both interventions will be applied once daily for 12 weeks. Patients will be instructed to avoid other depigmenting agents or procedures during the study period. The primary outcome will be the reduction in Melasma Area and Severity Index (MASI) scores. MASI scores will be assessed at baseline, at 4 week and 12 weeks follow up using standardized clinical photographs and independent evaluator scoring. Efficacy of treatment will be noted as per operational definition. Data Analysis Procedure: The collected data will be analyzed using IBM SPSS version 23. Quantitative variables such as age , duration of melasma and MASI scores will be presented as mean ± standard deviation (SD) or Median (IQR) after assessing data normality using the Shapiro-Wilk test. For qualitative variables like gender, residence and efficacy (Poor/Good/Excellent) ,frequencies and percentages will be calculated. Efficacy will be stratified among both groups and chi square or fishers exact test will be applied with p value of ≤0.05 will be considered significant. Additionally, effectiveness will also be stratified against age group , duration of melasma, socioeconomic status, baseline melasma score and gender to control effect modifier and post stratification chi square or fishers exact test will be applied with p value of ≤0.05 will be considered significant. References: 1. Tahoun AI, Mostafa WZ, Amer MA. Dermoscopic evaluation of tranexamic acid versus Vitamin C, with microneedling in the treatment of melasma: a comparative, split-face, single-blinded study. J Dermatol Treat. 2021;1-7. 2. Fahim M, Khoso H, Khan J, Gul H, Bakhtiar R. Efficacy of Intradermal Tranexamic Acid versus Topical 5% Magnesium Ascorbyl Phosphate in the Treatment of Melasma: A Head-to-Head Comparison. J Pak Assoc Dermatol. 2023;33(4):1412-1420. 3. Liu Y, Wu S, Wu H, Liang X, Guo D, Zhuo F. Comparison of the Efficacy of Melasma Treatments: A Network Meta-Analysis of Randomized Controlled Trials. Front Med. 2021;8:713554-58 4. Kaikati J, El Bcherawi N, Khater JA, Dib SM, Kechichian E, Helou J. Combination Topical Tranexamic Acid and Vitamin C for the Treatment of Refractory Melasma. J Clin Aesthet Dermatol. 2023;16(7):63-65. 5. Hasan SS, Saeed MY, Hamakarim HA. Topical Ascorbic Acid Mesotherapy with Microneedling versus Topical Tranexamic Acid Mesotherapy with Microneedling for Melasma: A Therapeutic Comparative Study. AMJ. 2024 ;9(3):142-50. 6. Zhou N, Tao J, Yi Z, Wu L, Liu Z, Yang B. Safety and efficacy of a picosecond 755-nm alexandrite laser combined with topical tranexamic acid in the treatment of melasma. J Cosmetic Dermatol. 2024 ;23(11):3579-84. 7. González-Molina V, Martí-Pineda A, González N. Topical Treatments for Melasma and Their Mechanism of Action. J Clin Aesthet Dermatol. 2022;15(5):19-28

Conditions

• Melasma

Interventions

Type	Name	Description
DRUG	Ethyl ascorbic acid topical application	The participants in this arm of study will only receive topical ethyl ascorbic acid once daily at night for 12 weeks
DRUG	Tranxemic acid topical application	The participants in this arm will receive only topical tranexamic acid once daily for 12 weeks

Timeline

• Start date: 2026-06-01
• Primary completion: 2026-11-30
• Completion: 2026-11-30
• First posted: 2026-04-13
• Last updated: 2026-04-13