Clinical assessment of the efficacy of tranexamic acid-niacinamide loaded niosome in comparison to tranexamic acid-niacinamide and hydroquinone conventional creams in melasma

The main purpose of this study is to assess the clinical efficacy of topical niosomal tranexamic acid-niacinamide formulation in melasma patients

A randomized, double-blinded, parallel-group, controlled trial on 102 patients, randomization through the block randomization technique (block size: 6) using Sealedenvelope.com site.

This study will take place in the Dermatology clinic of Faghihi Hospital, Shiraz. Patients will be divided into 3 groups and visited before therapy and then monthly up to month 3. This study will be double-blinded and patients and physicians are blind to the therapeutic options.

Inclusion criteria: Patients (male and female) with melasma between 18 and 50 years old; patients who have had melasma for at least 6 months, those who are capable of understand, read, and write and sign the informed consent form; and patients who are able to participate in sequential follow-up visits by physician. Exclusion criteria: Consumption of oral contraceptives; patients who are taking oral corticosteroids or topical corticosteroids on melasma lesions during the study; history of thyroid disorders, intolerance to the administered drugs; patients have had other hyperpigmentary disorders; pregnancy and lactation

The first group will receive topical niosomal tranexamic acid-niacinamide, the second group will receive conventional tranexamic acid-niacinamide cream, and the third (control) group will receive conventional 4% hydroquinnone cream . All patients will receive the formulations twice daily for 3 months (except for the hydroquinone group that will receive the blinded-label cold cream in the morning).

Skin Photography and calculation of modified Melasma Area Severity Index (mMASI) score and melanin index. Assessment of Melasma Quality of Life Scale (MELASQOL) questionnaire

Patients will be randomly divided into 3 treatment groups through the block randomization technique using Sealed Envelope software. Sealed Envelope software is used for block randomization of the samples. In this regard, the sample size (102 patients), the block size (6), and the number of treatment groups (3 groups) will be given to the software. Then, according to the inputs, a total of 102 patients will be randomly divided into 17 blocks and each block will contain 6 individuals. In addition, each block will contain an equal number of each treatment type. After that, through the Sealed Envelope software, a specified code number (ex. NB4) will be assigned to each patient. After formulation preparation according to the suggested blocks, each formulation will be put in an envelope and sealed, and then marked with a specified code number. The prepared sealed envelopes will be grouped in the aforementioned blocks and will be given to the physician. Each sealed envelope that is marked with a specified code number will be randomly allocated to each participant entered in the trial by the physician. So, the Sealed Envelope software will be used as a randomization tool and allocation concealment would be achieved through the sealed envelopes and specified codes that will be assigned to each participant. Only the principle investigator and the formulator will be aware of the treatment type of each sealed envelope and specified code number, while others are blinded.

In this study, all participants, the physician who will visit the patients and assess the response to therapy sequentially, those who will give the formulations to the patients, the statistical analyst, and the outcome analyzer will be blinded. However, the principle investigator, Safety Monitoring Board, the researcher who prepared the formulations, and the manuscript writers will be unblinded. It should be mentioned that all patients will be aware of the clinical trial and will be included in this study just after signing the informed consent form. Blinding will be performed through the recruitment of the suggested specified code numbers by the Sealed Envelope software. In this regard, each treatment (topical formulation) would be put in an envelope and sealed, and marked with a specified code number from the software. After that, the sealed envelopes will be further grouped in blocks. The prepared sealed envelopes that are grouped in 17 blocks (each block contains 6 envelopes) will be given to the physician. The physician will randomly allocate each sealed envelope to each participant who entered the trial. Therefore, only the principle investigator, Safety Monitoring Board, and the formulator will be aware of the treatment type of each specified code number of sealed envelopes, while the others are blinded.

All gathered deidentified individual participant data (IPD) would be shared where necessary.

Data would be available after the collection of required data from all participants or when any severe adverse reaction occurred. Data would be available at least for 5 years after the completion of this study.

Data would be available to healthcare authorities.

Data would be available on request.

Data would be available through direct communication with the project administrator.

Data would be available through direct communication with the project administrator. (Email address: smsamani@sums.ac.ir)