Efficacy and Safety of Non-Cross-Linked Sodium Hyaluronate Composite Solution Injection for Skin Condition Improvement: A Prospective, Multicenter, Randomized, Evaluator-Blinded, Blank-Controlled Superiority Trial

Background: Minimally invasive injectable therapies, including multi-component sodium hyaluronate composite formulations designed to improve skin quality through biological support of the dermal microenvironment, have gained increasing clinical interest, yet robust large-scale clinical evidence remains limited. Objective: To investigate the clinical efficacy and safety of an injectable sodium hyaluronate composite solution for improving overall skin quality and appearance. Methods: This was a prospective, multicenter, randomized, blank-controlled, superiority clinical trial involving 561 subjects, who were randomly assigned to either the treatment group or the control group. The primary efficacy endpoint was improvement in skin appearance as evaluated by investigators using the Global Aesthetic Improvement Scale (GAIS). Secondary endpoints included multidimensional assessments of skin quality parameters as well as subject-reported satisfaction. Safety was assessed through the incidence and severity of adverse events and serious adverse events throughout the study period. Results: The GAIS improvement rate was markedly higher in the treatment group compared with the control group (90.00% vs. 11.90%, P < 0.0001), and this superiority was consistently observed across different analysis populations. Secondary efficacy measures further demonstrated significant improvements in skin quality and high levels of subject satisfaction in the treatment group. Most treatment-emergent adverse events were mild to moderate, transient, and localized, with no unexpected safety signals identified. Conclusions: The injectable sodium hyaluronate composite solution demonstrated significant efficacy in enhancing skin appearance and overall skin quality, with a favorable and well-tolerated safety profile. These findings support its clinical application as a minimally invasive option for skin rejuvenation. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.