A controlled interventional study was conducted on 72 patients diagnosed with primary knee

osteoarthritis and managed at the Department of Rheumatology, Thai Nguyen National Hospital,

from October 2024 to October 2025. Patients were allocated into two groups: a control group

receiving standard pharmacologic therapy and an intervention group receiving the same regimen

supplemented with intra-articular administration of cross-linked hyaluronic acid enriched with

mannitol. Treatment efficacy was evaluated using changes in VAS pain scores, WOMAC indices, and

ultrasonographic findings at 1-month and 6-month follow-ups. Results: At 6 months, the intervention

group exhibited a statistically significant reduction in VAS scores (from 5.72 ± 0.15 to 1.39 ± 0.46;

p < 0.05), accompanied by substantial improvements across WOMAC pain, stiffness, and physical

function domains. Post-intervention ultrasonography revealed absence of joint effusion in 91.5%

of patients, and the prevalence of synovitis decreased significantly compared with baseline (p <

0.05). Conclusion: Intra-articular injection of cross-linked hyaluronic acid combined with mannitol

demonstrates favorable therapeutic efficacy and contributes to meaningful improvements in pain

relief and functional outcomes in patients with primary knee osteoarthritis.