Clinical Safety and Efficacy of Hyaluronic Acid-Niacinamide-Tranexamic Acid Injectable Hydrogel for Multifactorial Facial Skin Quality Enhancement with Dark Skin Lightening

Abstract

Facial aging is a complex process manifesting as skin hyperpigmentation, textural irregularities, and a diminished elasticity, hydration, and evenness of tone. The escalating demand for minimally invasive aesthetic interventions has driven the development of advanced hydrogel-based injectable formulations. This clinical study assessed the safety and efficacy of Hydragel A1, an injectable hydrogel containing hyaluronic acid (HA), niacinamide, and tranexamic acid (TXA), designed to simultaneously address multiple facets of facial skin aging. A cohort of 49 female participants underwent a series of objective and subjective assessments, including the Global Aesthetic Improvement Scale (GAIS), instrumental measurements (Antera 3D, Chromameter, Cutometer, Dermascan, Corneometer), and standardized photographic documentation at baseline (Day 0) and 14, 28, and 70 days post-treatment. The results demonstrated statistically significant improvements in skin hydration, texture, elasticity, and pigmentation following Hydragel A1 administration. Notably, no serious adverse events or significant injection site reactions were observed, confirming the favorable safety profile of the investigated device. Collectively, these findings underscore the potential of a combined HA, niacinamide, and TXA injectable formulation to provide a comprehensive approach to facial skin rejuvenation, effectively targeting multiple aging-related mechanisms.

Keywords: aesthetic medicine; clinical trial; dermal fillers; facial aging; hyaluronic acid; hyperpigmentation; injectable therapeutics; niacinamide; skin texture; tranexamic acid.

Figure 1

Results of IGAIS and SGAIS scores collected during the clinical study of the Hydragel A1 medical device. Detailed descriptions of the significance of the various grades are presented in Table S1. IGAIS, Investigator Global Aesthetic Improvement Scale; SGAIS, Subject Global Aesthetic Improvement Scale.

Figure 2

Images from three selected study patients, showing a visible improvement of skin radiance (i.e., from left [D–3], pre-baseline to right [D70]), both in terms of spot intensity and size of the dark spots. (A1,A2) Patient N° 17. (B1,B2) Patient N° 19. (C1,C2) Patient N° 26. Scale bars = 10 mm.

Figure 3

Clinical monitoring results using the Antera 3D device. (A) Texture score evolution. (B) Roughness “Ra” parameter evolution. (C) Roughness “Rq” parameter evolution. (D) Maximum height evolution. Error bars = 95% confidence interval. Statistical significance (i.e., p-value ≤ 0.001) was evidenced by three asterisks (***). Detailed statistical analysis results are reported in Table S3.

Figure 4

Results of Antera 3D imaging at various timepoints of the clinical study. (A1–A3) Imaging of the right cheek for patient N° 4. (A4–A6) Imaging of the left cheek for patient N° 4. (B1–B3) Imaging of the right cheek for patient N° 37. (B4–B6) Imaging of the left cheek for patient N° 37. Scale bars = 5 mm. R = right, L = left.

Figure 5

Results of DermaScan imaging at various timepoints of the clinical study. (A1–A3) Imaging of the right cheek for patient N° 15. (B1–B3) Imaging of the left cheek for patient N° 24. (C1–C3) Imaging of the right cheek for patient N° 26. (D1–D3) Imaging of the right cheek for patient N° 30. (E1–E3) Imaging of the right cheek for patient N° 43. Scale bars = 2 mm. R = right, L = left.

Figure 6

Clinical monitoring results using the Chromameter device. (A1,A2) ∆L * parameter (lightness) distribution evolution per patient between 28 days and 70 days of follow-up. (B) a * parameter (redness) evolution. (C) b * parameter (yellow–blue axis) evolution. (D) ITA° parameter (Individual Typology Angle) evolution. Error bars = 95% confidence interval. Statistical significance (i.e., p-value ≤ 0.001) was evidenced by three asterisks (***). Detailed statistical analysis results are reported in Tables S5 and S6.

Figure 7

Clinical monitoring results using the Cutometer device. (A) “Uf” parameter (maximum skin deformation) evolution. (B) “Ua/Uf” parameter (gross elasticity) evolution. (C) “Ur/Ue” parameter (net elasticity) evolution. Error bars = 95% confidence interval. Statistical significance was evidenced by two asterisks (i.e., “**” for p-value ≤ 0.01) or by three asterisks (i.e., “***” for p-value ≤ 0.001). Detailed statistical analysis results are reported in Table S7.

Figure 8

Clinical monitoring results using the Corneometer device. Error bars = 95% confidence interval. Statistical significance (i.e., p-value ≤ 0.001) was evidenced by three asterisks (***). Detailed statistical analysis results are reported in Table S7.