Study of Uterine Prolapse Procedures - Randomized Trial

Uterovaginal Prolapse Clinical Trial

— SUPeR  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01802281
• Other study ID #: PFDN-24P01
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 1, 2013
• Est. completion date: October 31, 2024

Study information

• Verified date: August 2023
• Source: NICHD Pelvic Floor Disorders Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 183
• Est. completion date: October 31, 2024
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Women aged 21 or older who have completed child -bearing

2. Prolapse beyond the hymen (defined as Ba, Bp, or C > 0 cm)

3. Uterine descent into at least the lower half of the vagina (defined as point C> -TVL/2) )

4. Bothersome bulge symptoms as indicated on question 3 of the PFDI-20 form relating to 'sensation of bulging' or 'something falling out'

5. Desires vaginal surgical treatment for uterovaginal prolapse

6. Available for up to 60 month follow-up

7. Amenorrhea for the past 12 months from either menopause or endometrial ablation

8. Not pregnant, not at risk for pregnancy or agree to contraception if at risk for pregnancy (only applicable to the rare endometrial ablation patient)

9. Eligible for no cervical cancer screening for at least 3 years

Exclusion Criteria:

1. Previous synthetic material (placed vaginally or abdominally) to augment POP repair

2. Known previous uterosacral or sacrospinous uterine suspension

3. Known adverse reaction to synthetic mesh or biological grafts; these complications include but are not limited to erosion, fistula, or abscess

4. Chronic pelvic pain

5. Pelvic radiation

6. 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).

7. 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)

8. 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

9. Indication for ovarian removal (adnexal mass, BRCA 1/2 positivity, family history of ovarian cancer)

10. Current condition of amenorrhea caused by exogenous sex steroids or hypothalamic conditions.

Related Conditions & MeSH terms

• Prolapse
• Uterovaginal Prolapse

Intervention

Procedure:
• Uterosacral ligament suspension
The USLS procedure used in this protocol is a modification of the technique described by Shull.
• Uphold® LITE
The Uphold® procedure used in this protocol is a modification of the technique described by Vu and Goldberg.

Locations

Country	Name	City	State
United States	University of New Mexico Health Sciences Center, Department of Obstetrics and Gynecology	Albuquerque	New Mexico
United States	University of Alabama at Birmingham, Department of Obstetrics and Gynecology	Birmingham	Alabama
United States	Cleveland Clinic, Department OB/GYN	Cleveland	Ohio
United States	Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery	Durham	North Carolina
United States	University of California at San Diego, UCSD Women's Pelvic Medicine Center	La Jolla	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Magee-Women's Hospital, Department of Obstetrics and Gynecology	Pittsburgh	Pennsylvania
United States	Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery	Providence	Rhode Island

Sponsors (2)

Lead Sponsor	Collaborator
NICHD Pelvic Floor Disorders Network	Boston Scientific Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline PFDI 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline CRADI 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline POPDI 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline UDI 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline PFIQ 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline CRAIQ 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline POPIQ 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline UIQ 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Incontinence Severity Index	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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Functional Activity Scale	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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Body Part Pain Scale	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).	6, 12, 18, 24, 30, and 36 Months
Other	Change From Baseline Surgical Pain Scale Rest 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Surgical Pain Scale Normal 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Surgical Pain Scale Exercise 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Surgical Pain Scale Worst 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).	6, 12, 18, 24, and 36 Months
Other	Change From Baseline Body Image Scale	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.	6, 12, 18, 24, and 36 Months
Other	Change From Baseline PISQ-IR Sexually Active Average 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.	6, 12, 18, 24, and 36 Months
Other	POP-Q Ba Measurement	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.	12, 24, and 36 Months
Other	POP-Q Bp Measurement	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).	12, 24, and 36 Months
Other	POP-Q C Measurement	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.	12, 24, and 36 Months
Other	POP-Q TVL Measurement	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.	12, 24, and 36 Months
Other	PGI-I	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).	6,12, 18, 24, and 36 Months
Primary	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	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