Study of Uterine Prolapse Procedures - Randomized Trial (SUPeR)

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

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.

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.

The Uphold® procedure used in this protocol is a modification of the technique described by Vu and Goldberg.

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.

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.

The Pelvic Floor Distress Inventory is a 20-question, validated, self-reported instrument used to evaluate pelvic floor symptoms. It consists of an overall scale (range: 0-300) comprised of 3 sub-scales: 1. Pelvic Organ Prolapse Distress Inventory (range: 0-100), 2. Colorectal Anal Distress Inventory (range: 0-100), and 3. Urinary Distress Inventory (range: 0-100). The range of responses on the CRADI is 1-4 with (1) Not at all, (2) Somewhat, (3) Moderately, and (4), Quite a bit. Scores are calculated by multiplying the mean value of all questions answered by 25 for the scale. The range of responses is: 0-100 with 0 (least distress) to 100 (most distress). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Distress Inventory is a 20-question, validated, self-reported instrument used to evaluate pelvic floor symptoms. It consists of an overall scale (range: 0-300) comprised of 3 sub-scales: 1. Pelvic Organ Prolapse Distress Inventory (range: 0-100), 2. Colorectal Anal Distress Inventory (range: 0-100), and 3. Urinary Distress Inventory (range: 0-100). The range of responses on the CRADI is 1-4 with (1) Not at all, (2) Somewhat, (3) Moderately, and (4), Quite a bit. Scores are calculated by multiplying the mean value of all questions answered by 25 for the scale. The range of responses is: 0-100 with 0 (least distress) to 100 (most distress). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Distress Inventory is a 20-question, validated, self-reported instrument used to evaluate pelvic floor symptoms. It consists of an overall scale (range: 0-300) comprised of 3 sub-scales: 1. Pelvic Organ Prolapse Distress Inventory (range: 0-100), 2. Colorectal Anal Distress Inventory (range: 0-100), and 3. Urinary Distress Inventory (range: 0-100). The range of responses on the CRADI is 1-4 with (1) Not at all, (2) Somewhat, (3) Moderately, and (4), Quite a bit. Scores are calculated by multiplying the mean value of all questions answered by 25 for the scale. The range of responses is: 0-100 with 0 (least distress) to 100 (most distress). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Distress Inventory is a 20-question, validated, self-reported instrument used to evaluate pelvic floor symptoms. It consists of an overall scale (range: 0-300) comprised of 3 sub-scales: 1. Pelvic Organ Prolapse Distress Inventory (range: 0-100), 2. Colorectal Anal Distress Inventory (range: 0-100), and 3. Urinary Distress Inventory (range: 0-100). The range of responses on the CRADI is 1-4 with (1) Not at all, (2) Somewhat, (3) Moderately, and (4), Quite a bit. Scores are calculated by multiplying the mean value of all questions answered by 25 for the scale. The range of responses is: 0-100 with 0 (least distress) to 100 (most distress). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Impact Questionnaire short form (PFIQ-7) measuring the impact of bladder, bowel, and vaginal symptoms on a woman''s daily activities, relationships and emotions is composed of 3 scales of 7 questions each: the Urinary Impact Questionnaire (UIQ; range 0-100), the Pelvic Organ Prolapse Impact Questionnaire (POPIQ; range 0-100), and the Colorectal-Anal Impact Questionnaire (CRAIQ; range 0-100). The range of responses on the CRAIQ is 0-3 with (0) Not at all, (1) Somewhat, (2) Moderately, and (3), Quite a bit. Scores are calculated by multiplying the mean value of all answered questions for a scale by 100 divided by 3. The range of responses is: 0-100 with 0 (least negative impact) to 100 (most negative impact). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Impact Questionnaire short form (PFIQ-7) measuring the impact of bladder, bowel, and vaginal symptoms on a woman''s daily activities, relationships and emotions is composed of 3 scales of 7 questions each: the Urinary Impact Questionnaire (UIQ; range 0-100), the Pelvic Organ Prolapse Impact Questionnaire (POPIQ; range 0-100), and the Colorectal-Anal Impact Questionnaire (CRAIQ; range 0-100). The range of responses on the CRAIQ is 0-3 with (0) Not at all, (1) Somewhat, (2) Moderately, and (3), Quite a bit. Scores are calculated by multiplying the mean value of all answered questions for a scale by 100 divided by 3. The range of responses is: 0-100 with 0 (least negative impact) to 100 (most negative impact). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Impact Questionnaire short form (PFIQ-7) measuring the impact of bladder, bowel, and vaginal symptoms on a woman''s daily activities, relationships and emotions is composed of 3 scales of 7 questions each: the Urinary Impact Questionnaire (UIQ; range 0-100), the Pelvic Organ Prolapse Impact Questionnaire (POPIQ; range 0-100), and the Colorectal-Anal Impact Questionnaire (CRAIQ; range 0-100). The range of responses on the CRAIQ is 0-3 with (0) Not at all, (1) Somewhat, (2) Moderately, and (3), Quite a bit. Scores are calculated by multiplying the mean value of all answered questions for a scale by 100 divided by 3. The range of responses is: 0-100 with 0 (least negative impact) to 100 (most negative impact). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Pelvic Floor Impact Questionnaire short form (PFIQ-7) measuring the impact of bladder, bowel, and vaginal symptoms on a woman''s daily activities, relationships and emotions is composed of 3 scales of 7 questions each: the Urinary Impact Questionnaire (UIQ; range 0-100), the Pelvic Organ Prolapse Impact Questionnaire (POPIQ; range 0-100), and the Colorectal-Anal Impact Questionnaire (CRAIQ; range 0-100). The range of responses on the CRAIQ is 0-3 with (0) Not at all, (1) Somewhat, (2) Moderately, and (3), Quite a bit. Scores are calculated by multiplying the mean value of all answered questions for a scale by 100 divided by 3. The range of responses is: 0-100 with 0 (least negative impact) to 100 (most negative impact). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

Incontinence Severity Index measuring the severity of urinary incontinence is composed of 2 questions: frequency of leakage (0=Never,...,4=Every day/night) and amount of urine leakage (1=Drops, 2=small splashes, 3= More). The index score is calculated categorizing the product of the two responses. The range of responses is: 0 (no incontinence) to 12 (severe incontinence). Lower index scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

Functional Activity Scale measuring the impact of incontinence symptoms on a woman''s daily activities is composed of 13 questions about normal and physically strenuous daily activities. The range of responses on the individual questions is (1) No difficulty,... (5) Not able to do it. Scores are calculated by subtracting from the maximum sum (5*13=65) the product of the mean response and number of questions, then dividing by the total range of sums (65 - 13 = 52) and multiplying by 100. The range of responses is: 0-100 with 0 (worse functionality) to 100 (Better functionality). Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Body Part Pain Scale measuring the the pain experienced in the lower abdomen and pelvic region of the body is composed of 7 questions, each with a yes (1) or no (0) questions about experiencing pain followed by an intensity rating: 0 (No pain),..., 10 (Most intense). The score is calculated as the average of the responses. The range of responses is: 0-10 with 0 (No pain) to 10 (most intense pain). Lower scores indicate better function / fewer symptoms. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Surgical Pain Scale measuring the post-surgical pain experienced by a subject is composed of 4 questions: Pain at Rest (range 0-10), Pain with Normal Activities (range 0-10), Pain with Exercise (range 0-10), and Intensity of Worst Pain (range 0-10). Lower scores indicate better less pain. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Surgical Pain Scale measuring the post-surgical pain experienced by a subject is composed of 4 questions: Pain at Rest (range 0-10), Pain with Normal Activities (range 0-10), Pain with Exercise (range 0-10), and Intensity of Worst Pain (range 0-10). Lower scores indicate better less pain. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Surgical Pain Scale measuring the post-surgical pain experienced by a subject is composed of 4 questions: Pain at Rest (range 0-10), Pain with Normal Activities (range 0-10), Pain with Exercise (range 0-10), and Intensity of Worst Pain (range 0-10). Lower scores indicate better less pain. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Surgical Pain Scale measuring the post-surgical pain experienced by a subject is composed of 4 questions: Pain at Rest (range 0-10), Pain with Normal Activities (range 0-10), Pain with Exercise (range 0-10), and Intensity of Worst Pain (range 0-10). Lower scores indicate better less pain. Change = (Month [6, 12, 18, 24, and 36] Score - Baseline Score).

The Body Image Scale measuring how the subjects feel about their appearance and about any changes that may have resulted from their condition consists of 8 questions. The questions are scored from 0=Not at all,..., 3=Very much. The score is calculated by summing the responses and ranges from 0 to 24. Higher scores correspond to worse body image. Change = Month [6, 12, 18, 24, and 36] Score - Baseline Score.

The Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-revised (PISQ-IR) is a questionnaire measuring the impact of incontinence symptoms on sexual function and satisfaction. The PISQ-IR Sexually Active-Average Score (SA-AVG) ranges from 0 to 5 with higher scores indicating better function/satisfaction. The change from baseline outcome is calculated as the difference in score at 6, 12, 18, 24, and 36 months and the score at baseline.

The Pelvic Organ Prolapse Quantification (POPQ) Point Ba represents the most distal (i.e. most dependent) position of any part of the upper anterior vaginal wall (between the vaginal cuff or anterior vaginal fornix and Point Aa). Point Ba coincides with Point Aa (-3 cm) in a woman who has no anterior POP. In a woman with severe POP, Ba coincides with Point C.

The Pelvic Organ Prolapse Quantification (POPQ) Point Bp represents the most distal position of any part of the upper posterior vaginal wall (between the vaginal cuff or posterior vaginal fornix and Point Ap).

The Pelvic Organ Prolapse Quantification (POPQ) Point C is measured in cm relative to the hymen with negative values being proximal to the hymen and positive values distal to the hymen. Point C represents either the most distal edge of the cervix or the leading edge of the vaginal cuff after total hysterectomy.

The Pelvic Organ Prolapse Quantification (POPQ) Total Vaginal Length (TVL) is the length of the vagina from posterior fornix tothe hymen when Point C or D is reduced to its full normal position.

The Patient Global Impression of Improvement (PGI-I) is a patient-reported measure of perceived improvement with treatment, as assessed on a scale of 1 (very much better) to 7 (very much worse). Included here are participants who had improvement as indicated by a rating of 1 (very much better), 2 (much better).

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.

Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery

Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery

Nager CW, Visco AG, Richter HE, Rardin CR, Komesu Y, Harvie HS, Zyczynski HM, Paraiso MFR, Mazloomdoost D, Sridhar A, Thomas S; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Effect of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension on treatment failure in women with uterovaginal prolapse: 5-year results of a randomized clinical trial. Am J Obstet Gynecol. 2021 Aug;225(2):153.e1-153.e31. doi: 10.1016/j.ajog.2021.03.012. Epub 2021 Mar 12.

Lukacz ES, Sridhar A, Chermansky CJ, Rahn DD, Harvie HS, Gantz MG, Varner RE, Korbly NB, Mazloomdoost D; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network (PFDN). Sexual Activity and Dyspareunia 1 Year After Surgical Repair of Pelvic Organ Prolapse. Obstet Gynecol. 2020 Sep;136(3):492-500. doi: 10.1097/AOG.0000000000003992.

Nager CW, Visco AG, Richter HE, Rardin CR, Rogers RG, Harvie HS, Zyczynski HM, Paraiso MFR, Mazloomdoost D, Grey S, Sridhar A, Wallace D; NICHD Pelvic Floor Disorders Network. Effect of Vaginal Mesh Hysteropexy vs Vaginal Hysterectomy With Uterosacral Ligament Suspension on Treatment Failure in Women With Uterovaginal Prolapse: A Randomized Clinical Trial. JAMA. 2019 Sep 17;322(11):1054-1065. doi: 10.1001/jama.2019.12812. Erratum In: JAMA. 2021 Feb 16;325(7):696.