The clinical trial of alternative Relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial

Abstract

Background: Uterine leiomyomas are common for reproductive-aged women and affect women’s quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery(i.e., to reduce blood loss or surgical duration). Recently relugolix(40mg orally once daily) as a gonadotropin-releasing hormone (GnRH) receptor antagonist has proved its sufficient efficacy in suppressing estradiol levels without the transient estradiol flare-up compared with GnRH agonist. However long-term administration should not be permitted liable to for climacteric disorder or osteoporosis. And evidence is lacking on the actual efficacy and extent of adverse effects of the every other day dosing regimen. This trial aimed to prove non-inferiority in volume reduction effect on leiomyoma and safety(i.e., reduction of adverse effects) by every other day administration after two months of everyday administration compared to daily administration throughout the duration. Methods: A minimization adaptive randomized control trial(RCT) will be conducted. Patients(over 20 years old) harboring leiomyoma who will be undergoing surgical treatment will be invited to participate. Patients who are enrolled in the intervention group will receive every other day administration for 16 weeks after eight weeks of daily administration. Patients who are enrolled in the control group will receive daily throughout the 24 weeks. The primary outcome is the leiomyoma volume change rate and the secondary endpoints are the change rate of uterine volume, the occurrence of the climacteric disorder, genital bleeding days, change rate of serum hormone or bone turnover markers, and bone mineral density after 24 weeks compared to before administration. Discussion: This study will aim to prove both the non-inferiority in leiomyoma volume reduction and superiority in adverse effects occurrence reduction, which will provide a novel method to escape adverse effects with maintaining the effect of leiomyoma reduction. Trial registration: jRCTs051230078, registered 26 July 2023.