A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries

Abstract

Study objective: To evaluate the safety and efficacy of a new crosslinked hyaluronan (NCH) gel in reducing postoperative adhesions.

Design: Randomized controlled trial (Canadian Task Force classification I).

Settings: Seven departments of obstetrics and gynecology in China.

Patients: A total of 216 women scheduled for gynecologic laparoscopic surgery for primary removal of adhesions, myomas, ovarian cysts, or endometriotic cysts.

Interventions: Patients were randomized to receive either NCH gel or saline with 1:1 allocation.

Measurements and main results: All patients were evaluated using a modified American Fertility Society (mAFS) scoring system for the incidence, extent, and severity of pre-existing and postoperative adhesions at the 10 anatomic sites of ovaries/tubes and at the expanded 23 or 24 anatomic sites throughout the abdominopelvic cavity by laparoscopy. A total of 215 randomized patients were treated with either saline solution (108 of 108) or NCH gel (107 of 108), composing the full analysis set (FAS), and 196 patients (94 of 108 in the saline control group and 102 of 108 in the NCH gel group) completed the entire study, composing the per protocol set (PPS). The postoperative incidence of moderate or severe adhesions evaluated at the 10 sites (the primary endpoint for efficacy) was 27.7% in the control group and 9.8% in the NCH gel group, a difference of 14.4% (95% confidence interval [CI], 2.6%-20.6%) in the PPS, and 37.0% in the control group and 14.0% in the NCH gel group, a difference of 20.0% (95% CI, 8.9%-26.8%) in the FAS. The postoperative incidence of moderate or severe adhesions evaluated at the 24 sites was also significantly lower in the NCH gel group compared with the control group (5.9% vs 14.9%; p = .036) in the PPS. Also in the PPS, the NCH gel group had significantly lower postoperative adhesion scores of severity, extent, and mAFS: 60.0%, 50.8%, and 76.9%, respectively (median scores of the 10 sites; p = .002) and 48.5%, 50.0%, and 72.2% (median scores of the 24 sites; p = .001) lower than those recorded in the control group. No serious adverse events were observed, and the safety profile of NCH gel was comparable to that of saline control.

Conclusion: This study demonstrates that NCH gel is safe and significantly reduces adnexal adhesion formation and global adhesion formation throughout the abdominopelvic cavity after gynecologic laparoscopic surgery.

Trial registration: ClinicalTrials.gov NCT02166554.

Keywords: Adhesion prevention; Crosslinked hyaluronan gel; Laparoscopic surgery; Randomized controlled trial.