ZY5301 Tablet vs Placebo for Treatment of Chronic Pelvic Pain After Pelvic Inflammatory Disease: A Phase 2 Randomized Clinical Trial.

ABSTRACT

Importance Chronic pelvic pain (CPP) is the main sequela of pelvic inflammatory disease (PID), with no established treatment. ZY5301 tablets, an effective part preparation extracted from Ajuga decumbens Thunb. (jingucao), are being tested as a treatment for CPP caused by PID. Objective: To evaluate whether ZY5301 tablets are effective and safe for CPP treatment in women with PID. Design, Setting, and Participants: This placebo-controlled double-blind, dose-parallel, phase 2 randomized clinical trial was conducted in 9 hospitals in China. Female participants with CPP after PID were enrolled between October 16, 2020, and August 31, 2021. The data analysis was performed between December 2021 and March 2022. Interventions: Participants were randomized 111 to receive ZY5301 300 mg/d, ZY5301 600 mg/d, or placebo orally 3 times a day for 12 weeks. Main Outcomes and Measures: Visual analog scale (VAS) scores were the main measure used to evaluate the efficacy of ZY5301 in reducing CPP. The evaluation end points for VAS score included changes in mean weekly VAS score from baseline, area under the VAS score-time curve, pain remission (VAS score of 0 and 1) rate, and median time to pain remission. Safety was evaluated by the occurrence of treatment-emergent and treatment-related adverse events. Results: In total, 180 women were randomly assigned, and 177 were included in the efficacy analysis; thus, the full analysis set included 60 participants in the ZY5301 mg/d group (mean [SD] age, 37.4 [8.1] years), 58 in the ZY5301 600 mg/d group (mean [SD] age, 37.1 [7.9] years), and 59 in the placebo group (mean [SD] age, 38.9 [7.3] years). Participant characteristics at baseline were similar among the groups. After 12 weeks of treatment, the mean (SD) change in VAS score from the baseline was -2.1 (1.7) points, -3.5 (1.5) points, and -3.8 (1.7) points in the placebo, ZY5301 300 mg/d, and ZY5301 600 mg/d groups, respectively (P < .001). The pain remission rates at week 12 were 43.3% and 53.5% in the ZY5301 300 mg/d and ZY5301 600 mg/d groups, respectively, a significant difference compared with the placebo group (11.9%; P < .001). All the other end points showed similar improvements. The ZY5301 600 mg/d group had better efficacy than the ZY5301 300 mg/d group, but the difference was not significant. The safety analysis revealed no significant differences among groups. Conclusions and Relevance These findings show that ZY5301 tablet is efficacious for the relief of CPP with acceptable tolerability. Trial Registration ClinicalTrials.gov Identifier NCT05460546.