Traditional Chinese medicine (TCM) external therapies are suitable for knee arthralgia with localized lesions and prominent symptoms. Here, we evaluated the clinical efficacy and safety of Xiaobi gel patch, an external TCM application, which has effects of clearing heat, promoting diuresis, reducing inflammation and relieving pain, for patients with knee osteoarthritis (KOA) of the damp-heat obstruction type.

We conducted a prospective, multicenter, randomized, double-blind, placebo-controlled parallel-group clinical trial. In total, 214 patients were categorized into treatment and control groups in a 1:1 ratio. The treatment course was 2 weeks, with a 4-week follow-up. Seven centers in China participated in patient enrollment between November 12, 2021, and June 15, 2023. The observation indicators were the Western University of Ontario and McMaster University (WOMAC) Osteoarthritis Index scores, joint swelling index, TCM syndrome score, patient pain score (visual analog scale [VAS]), participant and investigator self-scores (VAS) for overall disease condition, and safety indicators.

All participants (107 each in the experimental and placebo groups) were included in the full analysis set (FAS) and safety set, while 197 met the inclusion criteria and were included in the per-protocol set (PPS). Baseline characteristics were comparable between the groups. In the FAS, the experimental group showed significant improvement in walking on flat ground and total stiffness scores and in total physical function and OA index scores. In the PPS, significant improvements were observed in walking on flat ground, total stiffness, and physical function scores. Secondary outcomes, including joint swelling score, TCM syndrome scores, patient- and investigator-reported overall disease condition, showed trends favoring the treatment group but were not significant. No significant difference was observed in skin irritation or adverse events.

The Xiaobi gel patch provides significant analgesic effects, improves local symptoms, and is safe for patients with KOA and damp-heat obstruction syndrome, supporting its long-term clinical use.