Design of a Randomized Clinical Trial of Perioperative Vaginal Estrogen Versus Placebo With Transvaginal Native Tissue Apical Prolapse Repair (Investigation to Minimize Prolapse Recurrence of the Vagina using Estrogen: IMPROVE)

Objectives To provide the rationale and design for a randomized, double-blind clinical trial of conjugated estrogen vaginal cream (applied for at least 5 weeks preoperatively and continued twice-weekly through 12 months postoperatively) compared with placebo in postmenopausal women with symptomatic pelvic organ prolapse undergoing a standardized transvaginal native tissue apical repair. Methods Study population, randomization process, study cream intervention, masking of participants and evaluators, placebo cream manufacture, standardized surgical intervention, and collection of adverse events are described. The primary outcome of surgical success is a composite of objectively no prolapse beyond the hymen and the vaginal cuff descending no more than one third the vaginal length; subjectively, no sense of vaginal pressure or bulging; and no retreatment for prolapse at 12 months. Time-to-failure postoperatively will be compared in the 2 groups with continued surveillance to 36 months. Secondary outcomes assessed at baseline, preoperatively (ie, after at least 5 weeks of study cream), and postoperatively at 6 month intervals include validated condition-specific and general quality-of-life metrics, overall impression of improvement, sexual function, vaginal atrophy symptoms, and body image. Challenges unique to this study include design and manufacture of placebo and defining and measuring study drug adherence. Results Recruitment of 204 women is complete with 197 randomized. There have been 174 surgeries completed with 15 more pending; 111 have completed their 12 month postoperative visit. Conclusions This trial will contribute evidence-based information regarding the effect of perioperative vaginal estrogen as an adjunct therapy to standardized transvaginal native tissue prolapse surgical repair.

Automated summary

This study outlines the rationale and design for a clinical trial comparing conjugated estrogen vaginal cream with placebo in postmenopausal women with pelvic organ prolapse undergoing a native tissue apical repair. The main outcome is surgical success at 12 months based on objective and subjective criteria, with time-to-failure compared up to 36 months postoperatively. Secondary outcomes include quality-of-life metrics, sexual function, vaginal atrophy symptoms, and body image.