Apical Suspension Repair for Vault Prolapse In a Three-Arm Randomized Trial Design

Three Arm Apical Suspension Trial for Post-Hysterectomy Vault Prolapse: Prospective Randomized Trial Involving Sacral Colpopexy, Transvaginal Mesh and Native Tissue Apical Repair

Sponsors

Lead Sponsor: NICHD Pelvic Floor Disorders Network

Collaborator: The Cleveland Clinic
University of Alabama at Birmingham
University of California, San Diego
Duke University
University of New Mexico
Women and Infants Hospital of Rhode Island
RTI International
University of Pennsylvania
University of Pittsburgh
Kaiser Permanente
University of Texas Southwestern Medical Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Source NICHD Pelvic Floor Disorders Network
Brief Summary

The study is a multi-center, randomized, surgical trial of women with symptomatic post-hysterectomy apical (cuff) prolapse desiring surgical treatment. This study will compare the three available surgical treatments performed in usual practice. The purpose of this study is to compare two commonly performed mesh apical repair (sacral colpopexy vs. Apical Transvaginal Mesh) and vaginal native tissue apical repairs with mesh reinforced repairs. The primary outcome is measured over time (up to 60 months) using a survival analysis approach. The investigators hypothesize that treatment failure will not differ between vaginally and abdominally placed mesh for vault vaginal prolapse, and mesh repairs (regardless of route of implantation) will be superior to native tissue apical suspension.

Detailed Description

The primary purpose of this three arm randomized clinical trial is to determine if apical transvaginal mesh placement is non-inferior to sacral colpopexy for anatomic correction of post-hysterectomy vaginal vault prolapse and to determine if mesh reinforced repairs performed by abdominal or vaginal approach are superior to native tissue vaginal repair. This trial has the following primary aims: 1. To determine if Apical Transvaginal Mesh is non-inferior to Sacral Colpopexy for anatomic correction of post-hysterectomy vaginal vault prolapse at time points through 3 years. 1A. In the case where Apical Transvaginal Mesh is shown to be statistically significantly non-inferior to Sacral Colpopexy for anatomic correction of post-hysterectomy vaginal vault prolapse at time points through 3 years, to determine if Apical Transvaginal Mesh is superior to Sacral Colpopexy for anatomic correction of post-hysterectomy vaginal vault prolapse at time points through 3 years. 2. To determine if Sacral Colpopexy is superior to Native Tissue Repair for anatomic correction of post-hysterectomy vaginal vault prolapse at time points through 3 years. 3. To determine if Apical Transvaginal Mesh is superior to Native Tissue Repair for anatomic correction of post-hysterectomy vaginal vault prolapse at time points through 3 years. Additional secondary aims include: 1. Evaluate the development of a valid and reliable Global Composite Outcome that balances adverse events and patient-centered outcomes to anatomic definitions of failure and success. 2. Determine the impact of preoperative frailty and mobility on surgical treatment outcomes and postoperative complications of older women following surgical correction of apical pelvic organ prolapse. 3. Evaluate the patient's perspective about adverse events and their role in patient decision-making outcomes. The aims include comparing patient versus surgeon rankings of complication grade, outcome, expectedness and seriousness, to estimate the association between patient rankings of adverse events (AEs) with decision-making and quality of life outcomes and to determine if their perspective about AEs changes over time.

Overall Status Active, not recruiting
Start Date March 2016
Completion Date February 2021
Primary Completion Date February 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Surgical Treatment Success Up to 60 months using a survival treatment analysis approach
Secondary Outcome
Measure Time Frame
Predictors of treatment failure, with treatment failure being a binary outcome as defined for the Primary Outcome Baseline, 6, 12, 24, 36, 48, and 60 months
Effect of treatment on how a woman feels (her perceptions and attitudes) about her body (Body Image) as measured by the mean score for each treatment group on the body image scale. Baseline, 6, 12, 24, 36, 48, and 60 months
Cost of surgical procedures as measured by mean direct and indirect costs for participants in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Treatment arm mean levels of anatomic: Pelvic Organ Prolapse Quantification (POPQ) System values (Aa, Ap, Ba, Bp, C) determined from anatomic measures. Baseline, 6, 12, 24, 36, 48, and 60 months
Proportion of participants in each treatment group with POPQ levels of C > -2/3 TVL Baseline, 6, 12, 24, 36, 48, and 60 months
Mean levels in each treatment group of maximum extent of prolapse (Defined as leading edge of prolapse-Ba, C, Bp). Baseline, 6, 12, 24, 36, 48, and 60 months
Proportion of patients within each treatment group with adequate prolapse improvement as measured by Patients Global Impression of Improvement (PGI-I) Baseline, 6, 12, 24, 36, 48, and 60 months
Mean overall prolapse symptoms using Pelvic Organ Prolapse Distress Inventory (POPDI-6) scores (sub-scale of PFDI-20) Baseline, 6, 12, 24, 36, 48, and 60 months
Length of urinary complications after surgery as measured by duration of postoperative catheterization Baseline, 6, 12, 24, 36, 48, and 60 months
Postoperative urinary success as measured by mean Urogenital Distress Inventory (UDI-6) scores (sub-scale of PFDI-20) Baseline, 6, 12, 24, 36, 48, and 60 months
Urinary dysfunction as measured by proportion of participants in each group with de novo voiding dysfunction. Baseline, 6, 12, 24, 36, 48, and 60 months
Urinary incontinence as measured by proportion of participants in each group with stress, urge, or mixed incontinence Baseline, 6, 12, 24, 36, 48, and 60 months
Quality of sexual/body image after surgery as measured by mean Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-revised (PISQ-IR) and Body Image in the Pelvic Organ Prolapse Questionnaire (BIPOP) scales in each treatment group Baseline, 6, 12, 24, 36, 48, and 60 months
Quality of sexual/body image after surgery as measured by of proportion of participants in each treatment group with de novo dyspareunia Baseline, 6, 12, 24, 36, 48, and 60 months
Bowel function measured as the Colorectal-anal Distress Inventory (CRADI-8) scores (sub-scale of PFDI-20) in each treatment group Baseline, 6, 12, 24, 36, 48, and 60 months
General quality of life as measured by mean quality of life scales in each treatment group on 4 Short-Form Health Survey Support Loss (SF-12) total scores and physical function and mental function sub-scales Baseline, 6, 12, 24, 36, 48, and 60 months
Pelvic QOL as measured by mean Pelvic Floor Impact Questionnaires (PFIQ) score in each treatment arm Baseline, 6, 12, 24, 36, 48, and 60 months
Level of function as measure by mean Functional Activity Scale score for each treatment group Baseline, 6, 12, 24, 36, 48, and 60 months
Patient Regret/Satisfaction after surgery as measured by mean scores in each treatment group of Regret with Decision Regret Scale (DRS-PFD), and Satisfaction with Decision Scale (SDS-PFD) Baseline, 6, 12, 24, 36, 48, and 60 months
Interoperative blood loss in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Extent of interoperative complications in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Interoperative safety in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Risk of mesh-related complications in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Risk of surgical pain in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Risk of post-surgical complications in each treatment group Baseline, 6, 12, 24, 36, 48, and 60 months
Risk of need for additional treatment/subsequent procedures for pelvic floor disorders. Baseline, 6, 12, 24, 36, 48, and 60 months
Risk of vaginal scarring requiring medical or surgical intervention in each treatment group. Baseline, 6, 12, 24, 36, 48, and 60 months
Rates of vaginal shortening (TVL<6cm), de novo dyspareunia, or worsening dyspareunia. Baseline, 6, 12, 24, 36, 48, and 60 months
Enrollment 363
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Open, Robotic, or Laparoscopic

Description: Sacral Colpopexy is a surgery performed either through an incision in the abdomen or through several small incisions with the help of a laparoscope (a slender tube) or robot. The surgery is done with a permanent synthetic (man-made) mesh. The mesh is sutured (stitched) to the vagina and sacrum (tail bone) and is used as reinforcement. It provides additional support to weakened tissues and/or muscles.

Arm Group Label: Sacral Colpopexy

Intervention Type: Procedure

Intervention Name: Transvaginal Native Tissue Repair

Description: Transvaginal Native Tissue Repair is a surgery performed with an incision through the vagina (transvaginal). The surgery is done using both permanent and absorbable sutures (stitches), to support weakened tissue and/or muscles, and attach the top of the vagina to ligaments in the pelvis (either to the sacrospinous ligament or uterosacral ligament).

Arm Group Label: Transvaginal Native Tissue Repair

Intervention Type: Procedure

Intervention Name: Uphold™ LITE

Description: Transvaginal Mesh Repair is a surgery performed with an incision through the vagina (transvaginal). The surgery is done with a permanent synthetic (man-made) mesh. The mesh is attached to ligaments in the pelvis and is used to reinforce natural tissue and/or muscles, which are no longer able to provide support to the vagina.

Arm Group Label: Apical Transvaginal Mesh Repair

Eligibility

Criteria:

Inclusion Criteria: 1. Women age 21 or older 2. Prior total hysterectomy (no cervix present) 3. Prolapse beyond the hymen (defined as Ba, C, or Bp > 0 cm) 4. Vaginal cuff descent into at least the lower two thirds of the vagina (defined as point C> -2/3 TVL) 5. Bothersome bulge symptoms as indicated on question 3 of the PFDI-20 form relating to 'sensation of bulging' or 'something falling out' 6. Desires surgical treatment for post-hysterectomy vaginal prolapse 7. Available for up to 60 month follow-up Exclusion Criteria: 1. Previous synthetic material or biologic grafts (placed vaginally or abdominally) to augment POP repair including anterior, posterior and/or apical compartments 2. Known previous formal SSLS performed for either uterovaginal or post-hysterectomy vaginal vault prolapse * 3. Known adverse reaction to synthetic mesh or biological grafts; these complications include but are not limited to erosion, fistula, or abscess 4. Unresolved chronic pelvic pain-active 5. Prior abdominal or pelvic radiation 6. Contraindication to any of the index surgical procedures - Known Horseshoe Kidney or Pelvic Mass overlying the sacrum - Active diverticular abscess or active diverticulitis - Shortened vaginal length (<6 cm TVL) - NOTE: - Only documented SSLS will be an exclusion. - Mesh used for only mid-urethral sling will NOT be an exclusion - If prior POP repair is unknown and unable to be documented, subjects will be eligible based on clinician judgment. The investigator will examine and assess for evidence of mesh or graft if no evidence of mesh or graft is present on examination subject remains eligible.

Gender: Female

Minimum Age: 21 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Shawn Menefee, MD Study Chair Kaiser Permanente San Diego
Location
Facility:
University of Alabama at Birmingham | Birmingham, Alabama, 35233, United States
University of California at San Diego | San Diego, California, 92037, United States
Kaiser Permanente | San Diego, California, 92110, United States
University of New Mexico | Albuquerque, New Mexico, 87131, United States
Duke University | Durham, North Carolina, 27707, United States
Cleveland Clinic | Cleveland, Ohio, 44195, United States
University of Pennsylvania | Philadelphia, Pennsylvania, 19118, United States
University of Pittsburgh | Pittsburgh, Pennsylvania, 15213, United States
Brown/Women and Infants Hospital of Rhode Island | Providence, Rhode Island, 02903, United States
University of Texas Southwestern Medical Center | Dallas, Texas, 75390, United States
Location Countries

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Sacral Colpopexy

Type: Active Comparator

Description: Sacral Colpopexy performed via open, robotic, or laparoscopic procedure.

Label: Transvaginal Native Tissue Repair

Type: Active Comparator

Description: Transvaginal Native Tissue Repair: Sacrospinous Ligament Suspension (SSLS) and Uterosacral Ligament Suspension (USLS)

Label: Apical Transvaginal Mesh Repair

Type: Active Comparator

Description: Uphold™ LITE

Acronym ASPIRe
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Factorial Assignment

Primary Purpose: Treatment

Masking: Single (Outcomes Assessor)

Source: ClinicalTrials.gov