Effectiveness and safety of intra-articular hyaluronic acid SEMICAL GEL-B CROSS therapy in knee osteoarthritis (SEM-ART1): Study protocol for a randomized, placebo controlled, double-blind, cross-over clinical trial.

Abstract

This study aims to evaluate the effectiveness and safety of a single intra-articular injection of high-dose cross-linked hyaluronic acid on pain, physical function, muscle strength, and quality of life in patients with knee osteoarthritis. This randomized, double-blind, placebo-controlled, cross-over clinical trial includes 102 adults with symptomatic knee osteoarthritis (Kellgren-Lawrence grade II-III). Participants will be allocated using stratified randomization based on radiographic severity and laterality. Patients will receive either intra-articular hyaluronic acid (Semical Gel-B Cross, 90 mg/3 mL) or isotonic saline (3 mL of 0.9% NaCl), followed by cross-over at the 3-month evaluation. Outcomes will be assessed at baseline and at 3, 6, 9, and 12 months. The primary efficacy endpoint is the between-group difference in WOMAC pain score at the 3-month assessment prior to cross-over. Secondary outcomes include VAS pain, WOMAC physical function and stiffness scores, isometric quadriceps and hamstring strength, quality of life (SF-36), the 6-minute walk test, the 5-times sit-to-stand test, analgesic use, and adverse events. Treatment response will additionally be categorized as "absolute responders" (≥50% and ≥20-point improvement in VAS) and "responders" (≥20% and ≥10-point improvement). Sample size was calculated using G*Power (effect size 0.5, 80% power), yielding 102 participants. Statistical analyses will include both intention-to-treat and per-protocol approaches. This study will provide 3-month efficacy data and long-term (3-12 months) safety outcomes for high-dose intra-articular hyaluronic acid compared with placebo. Findings are expected to inform clinical decision-making regarding symptom relief, functional improvement, and the safety profile of cross-linked HA formulations in knee osteoarthritis. ClinicalTrials.gov: NCT06141018.