Study of Uterine Prolapse Procedures - Randomized Trial

Study Overview
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Brief Summary
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The primary purpose of this randomized clinical trial is to compare the effectiveness and safety of two transvaginal apical suspension strategies for uterovaginal prolapse: a mesh augmented hysteropexy versus vaginal hysterectomy and uterosacral ligament suspension (USLS). The primary aim is to determine whether treatment success in women who undergo the above strategies differ at time points through 3 years. A supplemental study investigates anterior vaginal wall movement resulting from descent or rotation of the vaginal apex and/or anterior vaginal elongation, in women in both of the study arms of SUPeR.

Detailed Description
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The study population will be adult women (>21 years of age) with symptomatic uterovaginal prolapse at or beyond the hymen who desire vaginal surgical management. This study is intended to be done only on women who have completed child-bearing and have an inactive uterus, defined as amenorrhea for 1 year. Therefore women will be postmenopausal or will have amenorrhea from an endometrial ablation. Amenorrhea caused from exogenous steroids, or hypothalamic disorders will not allow inclusion. Participants will be obtained from the clinic population of each of the eight Pelvic Floor Disorders Network (PFDN) sites. Participants will be randomly assigned to have either vaginal hysterectomy and USLS or mesh hysteropexy suspension for treatment of their uterovaginal prolapse. The surgical assignment will be revealed in the operating room, after the participant is under anesthesia. Participants will be followed for at least 36-months (3-years) post surgery and up to a maximum of 60-months (5-years). Follow-up data will be obtained during in-person clinic visits, and study staff who are masked to the surgical assignment will be the primary person who obtain follow-up data. Although the primary study outcome does not depend on masked participants and blinded evaluators, several important participant reported secondary aims are subject to reporting bias if the participant is aware of her study assignment. Therefore, study participants, coordinators, and nurses will be masked to the study assignment. Study surgeons and anatomic evaluators will be unmasked. Evaluators conducting the POPQ exam will be a co-investigator, fellow or other qualified nurse who did not perform the study surgery. Surgical failure rates will be compared using survival analysis approaches appropriate for interval censored data (classic log-rank tests and survival models using a generalized linear model approach with a complementary log-log link) and secondary outcomes will be reported as rates in each group or as group means and evaluated with the appropriate parametric or nonparametric statistical tests. Throughout the study, the PFDN Data Safety and Monitoring Committee (DSMB) will review study data and decide if the study can or cannot continue. Additionally, this study will adhere to the CONSORT guidelines for performing and reporting randomized controlled trials (Begg et al 1996). Women who are eligible but decline enrollment will be characterized in a manner consistent with CONSORT requirements.

Official Title
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A Randomized Trial of Vaginal Surgery for Uterovaginal Prolapse: Vaginal Hysterectomy With Native Tissue Vault Suspension vs. Mesh Hysteropexy Suspension

Conditions
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Uterovaginal Prolapse

Intervention / Treatment
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* Procedure: Uterosacral ligament suspension
* Procedure: Uphold® LITE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 21 or older who have completed child -bearing Prolapse beyond the hymen (defined as Ba, Bp, or C > 0 cm) Uterine descent into at least the lower half of the vagina (defined as point C> -TVL/2) ) Bothersome bulge symptoms as indicated on question 3 of the PFDI-20 form relating to 'sensation of bulging' or 'something falling out' Desires vaginal surgical treatment for uterovaginal prolapse Available for up to 60 month follow-up Amenorrhea for the past 12 months from either menopause or endometrial ablation Not pregnant, not at risk for pregnancy or agree to contraception if at risk for pregnancy (only applicable to the rare endometrial ablation patient) Eligible for no cervical cancer screening for at least 3 years Exclusion Criteria: Previous synthetic material (placed vaginally or abdominally) to augment POP repair Known previous uterosacral or sacrospinous uterine suspension Known adverse reaction to synthetic mesh or biological grafts; these complications include but are not limited to erosion, fistula, or abscess Chronic pelvic pain Pelvic radiation Cervical elongation- defined as an expectation that the C point would be Stage 2 or greater postoperatively if a hysteropexy was performed. (Note: cervical shortening or trachelectomy is not an allowed intraoperative procedure within the hysteropexy treatment group). Women at increased risk of cervical dysplasia requiring cervical cancer screening more often than every 3 years (e.g. HIV+ status, immunosuppression because of transplant related medications, Diethylstilbestrol (DES) exposure in utero, or previous treatment for cervical intraepithelial neoplasia (CIN)2, CIN3, or cancer) Uterine abnormalities (symptomatic uterine fibroids, polyps, endometrial hyperplasia, endometrial cancer, or any uterine disease that precluded prolapse repair with uterine preservation in the opinion of the surgeon Indication for ovarian removal (adnexal mass, BRCA 1/2 positivity, family history of ovarian cancer) Current condition of amenorrhea caused by exogenous sex steroids or hypothalamic conditions.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hysteropexy<br>Uphold® LITE | Procedure: Uphold® LITE<br>* The Uphold® procedure used in this protocol is a modification of the technique described by Vu and Goldberg.<br>|
| Active Comparator: Hysterectomy and USLS<br>Vaginal hysterectomy and uterosacral ligament suspension (USLS) | Procedure: Uterosacral ligament suspension<br>* The USLS procedure used in this protocol is a modification of the technique described by Shull.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Failure | Failure was defined as any of the following: retreatment for prolapse, any POP-Q measure beyond the hymen, or presence of bother on PFDI vaginal bulge question. Under the permanent failure state assumption, the number of participants shown at each visit includes all participants who were still participating in the study or had a failure outcome prior their withdrawal. Similarly, the denominator number of participants for the cumulative failure at each visit includes all participants who were still participating in the study and attended the visit or had any failure outcome prior their withdrawal or missed visit. | 6 Months through 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| At-visit Failure | Failure was defines as any of the following: retreatment for prolapse, any POP-Q measure beyond the hymen, or presence of bother on PFDI vaginal bulge question. Under the transient failure state assumption, the number of participants shown at each visit includes all participants who were still participating in the study. Similarly, the denominator number of participants for the transient failure at each visit includes all participants who were still participating in the study and attended the visit or who missed the visit but had a retreatment failure outcome prior to their missed visit. | 6 months through 36 Months |