[Efficacy and safety of triptorelin acetate microspheres for injection versus triptorelin acetate for injection in Chinese patients with endometriosis: a multicenter, randomized, double-blind, phase Ⅲ non-inferiority clinical trial]

Objective: To evaluate the efficacy and safety of triptorelin acetate microspheres for injection compared with triptorelin acetate for injection in the treatment of endometriosis. Methods: A total of 392 patients with endometriosis were prospectively enrolled from 47 research centers across China between October 25, 2021, and February 14, 2023. Participants were randomly assigned in a 1∶1 ratio to either the experimental group (n=196) or the control group (n=196). Both groups received intramuscular injections of the respective drugs once every 4 weeks for a total of 6 doses. The primary efficacy endpoint was the percentage of subjects with suppressed estradiol levels after treatment. Secondary endpoints included pain relief, amenorrhea rate, changes in ovarian endometrioma diameter, and adverse drug reactions. Results: For the primary efficacy endpoint, the percentages of subjects with suppressed estradiol levels at week 12 in the experimental and control groups were 97.3% (177/182) and 98.4% (181/184), respectively. The rate difference was -1.1% (95%CI: -4.8% to 2.3%), the lower limit of the 95%CI for the rate difference was greater than the non-inferiority margin of -10%. Compared to baseline, visual analog scale (VAS) scores for dysmenorrhea and non-menstrual pelvic pain decreased at all post-treatment time points in both groups, with no statistically significant differences between two groups (all P>0.05). Estradiol, luteinizing hormone, and follicle stimulating hormone levels significantly decreased from baseline at all post-treatment time points in both groups (all P0.05). No significant differences were observed in amenorrhea rates between two groups at week 8, 12, and 24 post-treatment (all P>0.05). However, the time to menstruation recovery after drug discontinuation was significantly earlier in the experimental group than that in the control group (P=0.003). Carbohydrate antigen 125 levels significantly decreased from baseline at week 12 and 24 post-treatment in both groups (all P0.05). In the experimental group, only the diameter of the right ovarian endometrioma showed a significant decrease from baseline at week 24 post-treatment (P=0.016). In the control group, neither left nor right ovarian endometrioma diameters showed significant changes from baseline (all P>0.05). The overall incidence of adverse drug reactions was similar between the experimental and control groups [77.6% (152/196) vs 78.6% (154/196), respectively; P>0.05]. Conclusions: Triptorelin acetate microspheres for injection is an effective treatment for endometriosis. It could maintain low estrogen levels, consistently alleviate endometriosis-associated pain, achieve a high rate of amenorrhea during treatment, and reduce the size of ovarian endometrioma to some extent, demonstrating a favorable safety profile.