Clinical Efficacy Of Cortex Daphnes (Zushima) Patch In Patients With Symptomatic Knee Osteoarthritis: A Multicenter Non-Inferiority Randomized Controlled Clinical Trial

Background: Osteoarthritis (OA) is imposing substantial burdens on individuals and society with the aging population. Cortex Daphnes patch is widely used for symptomatic knee OA in China with a satisfying clinical efficacy; however, there is scant clinical evidence supporting its use. To evaluate its efficacy, we conducted a multicenter, non-inferiority, randomized, parallel-group study comparing Cortex Daphnes patch with topical nonsteroidal anti-inflammatory drugs in patients with knee OA (NCT02770950).Methods: A total of 264 symptomatic knee OA patients were treated with Cortex Daphnes or indomethacin cataplasms applied to affected sites once daily for 2 weeks. The primary outcome was improvement in knee pain on walking as assessed using a visual analog scale (VAS). The non-inferiority margin based on the full analysis population was set as -5 mm on the pain VAS. The secondary outcomes were changes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, WOMAC scores for pain, function and stiffness, the 36-item Short Form Health Survey (SF-36), and global assessment of knees by the patients. Responder rates for pain VAS, WOMAC total score, and WOMAC pain were also included in the secondary outcomes.Results: The Cortex Daphnes patch was non-inferior to indomethacin cataplasms for the primary outcome with a group difference (Cortex Daphnes patch-indomethacin cataplasm) of 2.1 mm (95% confidence interval: 2.1-6.4); similar results were found in the per-protocol population. For all other outcomes, no significant differences were found in the full analysis set or in the per-protocol analysis set, except the responder rates for WOMAC pain was higher in the Cortex Daphnes patch group than in the indomethacin cataplasm group (78.4 vs. 64.7%, p = 0.022) in the per-protocol analysis set. Overall, 28.8% patients in the Cortex Daphnes patch group and 9.8% in the indomethacin cataplasm group reported treatment-related adverse events, the vast majority of which were mild-to-moderate skin irritation, resulting in only 3.8 and 0.8% of patients dropping out, respectively.Conclusion: The Cortex Daphnes patch, which provides satisfactory analgesic efficacy and enhances the physical function of the knee, as well as improving quality of life, may be a promising alternative to knee OA.