A Randomized Trial of Vaginal Surgery for Uterovaginal Prolapse: Vaginal Hysterectomy With Native Tissue Vault Suspension vs. Mesh Hysteropexy Suspension
Phase: NA
Conditions: Uterovaginal Prolapse
Sponsor: NICHD Pelvic Floor Disorders Network

 
A Randomized Trial of Vaginal Surgery for Uterovaginal Prolapse: 
Vaginal Hysterectomy With Native Tissue Vault Suspension vs. 
Mesh Hysteropexy Suspension (SUPeR) 
 
NCT01802281 
 
Protocol Version 5.0 
 
October 9, 2020 
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
 
 
A Randomized Trial of Vaginal Surgery for Uterovaginal Prolapse: Vaginal Hysterectomy 
with Native Tissue Vault Suspension vs. Mesh Hysteropexy Suspension 
Short name: Study of Uterine Prolapse Procedures- Randomized Trial “SUPeR” 
 
Concept approval: July 21, 2011  
Mini-protocol approval: April 27, 2012 
Final approval: July 20, 2012 
Proposed amendment: October 9, 2020 
SUPeR Protocol Committee 
UCSD: Charles W. Nager, Chair  
Duke: Anthony G. Visco  
University of Pennsylvania: Heidi Harvie 
Cleveland Clinic: Marie Paraiso  
Brown: Charles Rardin 
UAB: Holly E. Richter 
 
University of New Mexico: Yuko Komesu 
University of Pittsburgh: Halina M. Zyczynski  
DCC RTI: Sonia Thomas, Amaanti Sridhar  
NICHD: Donna Mazloomdoost 
 
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 6, 2020 
ii 
 
TABLE OF CONTENTS 
A. 
STUDY AIMS 
1 
A.1 
Primary Aim 
1 
A.2 
Secondary Aims 
1 
B. 
BACKGROUND AND SIGNIFICANCE 
2 
B.1 
Rationale for the Vaginal Operations Being Proposed for this Study 
2 
B.2 
Rationale for Primary Outcome for this Study 
7 
B.3 
Study Design – Superiority Vs. Non-Inferiority 
9 
B.4 
Rationale for Including a Body Image Assessment 
9 
C. 
STUDY SCHEMA 
10 
C.1 
Study Design Diagram 
10 
D. 
STUDY POPULATION 
10 
E. 
INCLUSION AND EXCLUSION CRITERIA 
11 
F. 
PARTICIPANT SCREENING 
12 
G. BASELINE VISIT 
12 
H. 
RANDOMIZATION 
13 
I. 
APPOINTMENT SCHEDULING 
14 
J. 
INTERVENTIONS – SURGICAL INTERVENTIONS 
15 
J.1 
Surgeon Experience and Certification 
15 
J.2 
Description of Surgical Procedures 
17 
J.3 
Masking of Randomized Intervention 
19 
K. 
OUTCOME VISITS 
21 
L. 
TIMELINE OF VISITS/CALLS AND STUDY SCHEDULE 
21 
M. OUTCOME MEASURES 
22 
M.1 
Primary Outcome Measure 
22 
M.2 
Comparative Secondary Outcome Measures 
23 
N. 
SAMPLE SIZE/POWER CALCULATIONS 
30 
O. STATISTICAL DESIGN 
31 
P. 
ETHICAL CONCERNS, LIMITATIONS, AND INFORMED CONSENT 
32 
P.1 
Ethical Concerns 
32 
P.2 
Informed Consent 
33 
P.3 
Data and Safety Monitoring Board 
33 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 6, 2020 
iii 
P.4 
Reporting of Serious Adverse Events 
34 
Q. PROTOCOL COSTS 
34 
R. 
REFERENCES 
34 
S.  APPENDICES 
39 
Appendix A. Figures 
39 
Appendix B. Planned Study Timeline 
40 
T. 
AMENDMENT – REVISED: CLARIFICATION OF LENGTH OF SUBJECT 
PARTICIPATION 
41 
U. 
AMENDMENT: EXTENSION OF THE STUDY OF UTERINE PROLAPSE PROCEDURES-
RANDOMIZED TRIAL (SUPER) STUDY FOR LONG-TERM FOLLOW-UP TO 10 YEARS 
(E-SUPER) 
43 
 
 
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 6, 2020 
iv 
 
LIST OF TABLES 
 
Table 1. Vaginal Surgery Treatment Options for Uterovaginal Prolapse (non-obliterative 
procedures only) 
2 
Table 2. Uterosacral Vault Suspension Procedures 
3 
Table 3. Masking Summary 
20 
Table 4. Timeline of Measures 
22 
Table 5. Resource Utilization Data Collection and Price Data Source, by Utilization 
Category 
26 
Table 6. Body Image Scales 
29 
Table 7. Sample Size Calculations 
30 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
1 
A. 
Study Aims 
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 vs. vaginal hysterectomy and uterosacral ligament suspension.  
A.1 
Primary Aim 
1. To determine whether treatment success in women with symptomatic uterovaginal 
prolapse undergoing transvaginal mesh augmented hysteropexy differs in women 
undergoing vaginal hysterectomy and native tissue cuff suspension at time points 
through 3 years.  
Hypothesis –  
1. This study will test the null hypothesis that treatment success will not differ in women 
with symptomatic uterovaginal prolapse undergoing vaginal surgery with a synthetic 
mesh hysteropexy compared to women undergoing vaginal hysterectomy with native 
tissue vaginal suspension against the alternative hypothesis that success does differ for 
the treatment regimens. Operationally, the hypothesis will be tested using a two-sided 
log-rank test to test for a difference in the risk of failure across the two treatment arms to 
achieve an overall Type I error rate of 0.05 across the interim and final analyses.  
A.2 
Secondary Aims 
1. Secondary Efficacy Outcomes: To compare detailed anatomic and comprehensive 
functional outcomes (including prolapse, urinary, sexual, bowel and health-related 
quality of life (HRQOL)) in both groups. 
2. Safety: To measure and compare safety, adverse events (including mesh erosion and 
exposure), pain, and need for subsequent procedures in both groups.  
3. Predictors of Poor Outcomes: To determine if advanced prolapse, age, obesity, 
smoking, menopausal status, estrogens, previous prolapse surgery, and physical activity 
levels, alone or in combination, predict higher treatment failure.  
4. Cost-Effectiveness: To compare the cost-effectiveness of the two surgical approaches 
and relate the difference in cost of care between the two groups to differences in health 
utilities and health-related quality of life. 
5. Body Image: To describe changes in body image as measured by a validated scale, the 
Body Image Scale (BIS),.in a group of women undergoing mesh augmented hysteropexy 
or vaginal hysterectomy and to evaluate whether or not changes in sexual function are 
associated with changes in body image.  
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
2 
B. 
Background and Significance 
The apex of the vagina (either cervix or the vaginal cuff) is thought to be the keystone of pelvic 
organ support. Loss of apical support is usually present in women with prolapse that extends 
beyond the hymen.1,2 At least half of the observed variation in anterior compartment support 
may be explained by apical support.3 Adequate support for the vaginal apex is thought to be an 
essential component of a durable surgical repair for women with advanced prolapse.4,5 Because 
of the significant contribution of the apex to anterior vaginal support, surgical correction of the 
anterior and posterior walls may fail unless the apex is adequately supported.6 A better term for 
the most common prolapse conditions would be “uterovaginal” or “cuff-vaginal” prolapse. Apical 
suspension procedures can broadly be separated into those performed transvaginally and those 
performed abdominally. Abdominal procedures are performed via laparotomy or using 
conventional laparoscopic or robotically assisted-laparoscopic techniques.  While various 
abdominal and vaginal approaches exist, national data suggest that 80-90% of prolapse surgery 
is performed vaginally.7,8, 9 Transvaginal mesh systems were introduced to improve native tissue 
vaginal repairs without entry into the peritoneal cavity. FDA data released July 2011 noted that 
in 2010 approximately 300,000 women underwent surgical procedures to repair pelvic organ 
prolapse (POP), one-third used mesh, and 75% of mesh procedures were done transvaginally. 
This study is specifically addressing transvaginal surgical repair of uterovaginal prolapse.  
B.1 
Rationale for the Vaginal Operations Being Proposed for this Study 
Typical vaginal treatment options for prolapse are outlined in Table 1 below.  
Table 1. Vaginal Surgery Treatment Options for Uterovaginal Prolapse (non-obliterative 
procedures only) 
 
Uterovaginal Prolapse 
Native tissue options 
TVH-USLS 
(occ. TVH-SSLS) 
Native tissue hysteropexy  
Vaginal mesh options Hysteropexy (mesh strap technique) (e.g. Uphold®) 
Hysterectomy and vaginal mesh  
Native Tissue Options  
Uterovaginal Prolapse: Most uterovaginal prolapse is managed with a vaginal hysterectomy, +/- 
anterior and posterior colporrhaphy and other repairs as indicated. With minor degrees of 
uterine prolapse, culdeplasties (McCall, Mayo procedures) are performed to support the apex. 
With more advanced prolapse, a colpopexy is often performed. The most common procedure in 
academic centers is an intraperitoneal colpopexy (the uterosacral ligament suspension) (see 
Appendix A, Figure 1). The success rates for uterosacral operations were well summarized by 
Barber et al in ICI Chapter for POP as outlined in Table 2. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
3 
Table 2. Uterosacral Vault Suspension Procedures 
Year 
First Author 
No. of 
Pts. 
Mean Follow-
up Months 
(range) 
Definition of 
anatomic success* 
Anatomic 
success – all 
segments 
Anatomic 
recurrence by 
segment 
Reoperation for 
prolapse 
1997 
Jenkins10 
50 
(6-48) 
Not defined 
96% 
Anterior 4% 
None reported 
1999 
Comiter11 
100 
17 (6.5-35) 
Grade 0-1 
96% 
Apex 4% 
4 (4%) 
2000 
Barber12 
46 
15.5 (3.5-40) 
Stage 0/1 or stage 2 
without symptoms 
90% 
Apex 5%  
Anterior 5%  
Posterior 5% 
3 (6.5%) 
2000 
Shull13  
289 
Not stated 
Grade 0-1 
95% 
Apex 1%  
Anterior 3.5% 
Posterior 1.4% 
None reported 
2001 
Karram14  
168 
21.6 (6 -36) 
Grade 0-1 
88% 
Apex 1%  
Anterior or Posterior 
11% 
11 (5.5%) 
2003 
Amundsen15  
33 
28 (6-43) 
Stage 0 or 1 
82% 
Apex 6%  
Posterior 12% 
None reported 
2006 
Silva16  
72 
61.2 (42-90) 
Symptomatic stage 2 
or greater 
85% 
Apex 3%  
Anterior 7%  
Posterior 14% 
2 (3%) 
2006 
Antovska17  
32 
25 (9-42) 
Stage 0 or 1 
NR 
Apex 0% 
Anterior  
2007 
Wheeler18 
35 
24 (0-46) 
Stage 0 apical 
prolapse 
80% 
Apex 20% 
0 (0%) 
2009 
De Boer19  
48 
12 
Stage 0-1 
48% 
Apex 4.2% 
Anterior 47.9% 
Posterior 14.6% 
None Reported 
2011 
Doumouchtsis20 
42 
60 
Grade 0 of vaginal 
vault 
84.6% 
Apex 15.4% 
5 (11.9%) 
In summary, uterosacral vault suspension procedures have a low overall recurrence rate of 4-
18%, anterior vaginal recurrence rates of 1-6% and a reoperation rate of less than 7%. Ureteral 
injury rates of 1-11% are reported.   
Native Tissue Hysteropexy: Limited data are available on the success of native tissue vaginal 
uterine suspension (hysteropexy) procedures. Sacrospinous hysteropexy was first reported in 
1989.21 One randomized controlled trial (RCT) comparing sacrospinous suspension with or 
without vaginal hysterectomy showed higher recurrent apical prolapse without hysterectomy (21 
vs. 3%, p = 0.03) with no significant difference in recurrent anterior prolapse with hysterectomy 
(65 vs. 50%, p = 0.2).22 This study was limited by 7% post randomization change in surgical 
plan and low numbers (only 66 total participants). Cohort studies of sacrospinous hysteropexy 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
4 
suggest high apical failure rates in those with advanced prolapse, but small sample size 
prohibited definitive conclusions. Most of these studies used suture techniques for the 
sacrospinous hysteropexy, which tend to be unilateral, produce deviation of the cervix and 
vaginal axis and this procedure has not achieved any significant popularity in the 20 years since 
the initial report. There is one recently published report of a retrospective single author 
experience with a uterosacral hysteropexy techniques, but the pelvic organ prolapse 
quantification (POPQ) system was not used to measure the outcomes and the outcome 
assessor was often the surgeon.23 A survey of Pelvic Floor Disorders Network (PFDN) sites 
reveals rare performance of this procedure (approximately 25 total in last 5 years at 3 sites). In 
summary, although suture vaginal hysteropexy techniques have been available for more than 
20 years they are uncommonly performed and there are minimal published data on these 
procedures.  
Vaginal Mesh Options 
The FDA conducted a systematic review of the scientific literature on transvaginal mesh and in 
July 2011 published a report titled “Urogynecologic Surgical Mesh: Update on the Safety and 
Effectiveness of Transvaginal Placement for Pelvic Organ Prolapse.”24 The report noted that in 
2010 approximately 300,000 women underwent surgical procedures to repair POP, one-third 
used mesh, and 75% of mesh procedures were done transvaginally. Systematic reviews by the 
Society of Gynecologic Surgeons (SGS) found weak evidence for improved anterior anatomy 
when vaginal prolapse repairs were performed with synthetic mesh compared with native 
tissue.25 A systematic review of vaginal mesh kits for apical repair found they appear effective in 
restoring apical prolapse in the short-term, but long-term outcomes are unknown.26   
Many urogynecologists use transvaginal mesh for apical compartment prolapse, even after the 
July 2011 FDA notification on transvaginal mesh for prolapse. Despite widespread use of 
vaginal mesh for apical support in patients with and without uteri, there is a dearth of data on the 
results of these procedures and systematic reviews on vaginal mesh for the apical compartment 
are inconclusive. Well done studies are needed on vaginal mesh for the apical compartment for 
patient counseling and to establish retention of the uterus as a safe and effective treatment 
choice.   
Uterovaginal Prolapse: Vaginal mesh options for uterovaginal prolapse include hysteropexy with 
a mesh strap technique or hysterectomy and vaginal mesh apical suspension.   
Hysteropexy (Mesh Strap Technique): In the past, justifications for removal of the uterus include 
concerns regarding cervical hypertrophy, future cervical or uterine pathology, or even a non-
evidenced belief that the uterus organ itself is involved in the prolapse process. Uterine 
pathology is rare (< 1%) in women undergoing prolapse surgery.27 Thus, the common practice 
of hysterectomy at the time of vaginal prolapse repair is to facilitate apical suspension. While 
hysterectomy is the norm, it is not clear whether removing the uterus is necessary or leads to 
better results. Hysterectomy can have adverse effects; it is associated with menopause 4 years 
earlier than in women who did not have surgery28 and is associated with a 2-fold risk of ovarian 
failure.29 When presented with a scenario in which the participant receives preoperative 
counseling that the success of surgery is similar with and without hysterectomy, 66% indicated 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
5 
they would decline a hysterectomy (Frick AC et al, SGS 2011). A recent review on uterine-
sparing apical prolapse repair concluded that vaginal hysterectomy was not necessary.30 One 
purpose of this study is to compare a uterine-sparing technique (mesh hysteropexy and other 
native tissue vaginal prolapse repairs) with a vaginal hysterectomy utilizing native 
tissue/ligament suspension and other native tissue vaginal prolapse repairs.  
The concept of creating a mesh suspension bridge to support the cervix and vaginal apex to 
bilateral sacrospinous ligaments was initially developed by Petros31 with the infracoccygeal 
sacropexy; however, the trocar delivery system and multifilament mesh resulted in unacceptably 
high complication rates and is no longer on the market. The concept of this procedure evolved 
from a trocar placed device to a trocarless placement, with the most recent product developed 
by Boston Scientific (Uphold® and Uphold® LITE). This procedure is performed through an 
anterior approach using a synthetic monofilament mesh bridge which attaches the cervix to this 
mesh and then bilaterally to the sacrospinous ligament (see Appendix A, Figure 1). It is 
essentially a mesh hysteropexy technique, although the FDA predicate approval process did not 
allow it to be promoted and marketed as such. The most recent FDA approval was September 
14, 2011 for the Uphold® LITE Vaginal Support System indicated “for tissue reinforcement and 
stabilization of fascial structures of the pelvic floor for vaginal wall prolapse, where surgical 
treatment is intended, either as mechanical support or bridging material for the fascial defect.” 
The Uphold® LITE mesh has the same overall dimensions as the previous Uphold® mesh, but 
has a 75% increase in pore size, 38% reduction in weight, a 32% reduction in surface area ratio 
and is blue for enhanced visibility. As most literature would suggest that lighter, larger pore size 
mesh is preferable and may have less stress shielding (Moalli, AUGS, 2011), these changes are 
all considered positive, and for SUPeR we anticipate using the Uphold® LITE product. This 
Uphold® procedure results in a uterus in a more midline position with bilateral mesh sacral 
ligaments and theoretically is less likely to have suture pullout, asymmetry or extreme posterior 
deviation of the uterus. These mesh strap hysteropexy techniques allow the potential for 
decreased operative time and morbidity associated with hysterectomy. Theoretically, mesh 
exposure rates may be lower with these mesh strap hysteropexy techniques because of the 
smaller amount of mesh material used compared to other commonly performed anterior and 
posterior mesh kit procedures, the mesh straps are directed away from the vagina so that the 
mesh can be placed distant from incision lines. 
In a recently published single center study of 115 participants, 53 were Uphold® hysteropexy 
procedures32 at a median follow-up of 11.8 months (range 0.4-30.9 months). Using POP-Q > -1 
to define recurrence, the combined anterior apical recurrence rate was 1.89%, including no 
anterior (Ba > -1) and one apical (C > -1). Using POPQ > 0 there were no recurrences in Ba > 0 
or C > 0 compartment. The mesh exposure rate was 1.9%. In the overall group of 115 
participants, 13.4% (13/97) reported preoperative dyspareunia and 8.3% reported postoperative 
dyspareunia (8/97). Dyspareunia resolved in 12/13 with preoperative dyspareunia and was de 
novo in 6 participants – all 6 had perineorrhaphy. As noted earlier, over 15,000 Uphold® kits 
have been sold in the U.S. (personal communication 5/2011) but their usage for uterine 
prolapse vs. vault prolapse indications is not known. However, this number would make it 
significantly more common than any suture/native tissue/ligament hysteropexy technique. A 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
6 
recent study of 31 women randomized to hysterectomy or hysteropexy, both using 
polypropylene mesh, found no significant differences in outcomes.33, 34   
A review of clinicaltrials.gov reveals that there are 2 ongoing registered trials studying the 
Uphold® procedure as a hysteropexy:  
1. VAULT study (http://clinicaltrials.gov/ct2/show/NCT01377142?term=Vault&rank=1): 
“Vaginal Uphold Hysteropexy and Laparoscopic Sacral Hysteropexy for the Treatment of 
Uterovaginal Pelvic Organ Prolapse (VAULT)”. This multicenter trial is sponsored by the 
Foundation for Female Health Awareness and coordinated at the Cleveland Clinic with 
anticipated enrollment that will end in summer 2012. This study is not randomized and 
has a one-year outcome. Both groups retain their entire uteruses and the primary 
outcome is a composite outcome including cervix above the mid-vagina, absence of any 
prolapse beyond the hymen, absence of retreatment and absence of vaginal bulge 
symptoms. Secondary outcome measures include anatomic, symptomatic, short-term 
morbidity, pain and functional activity.   
2. HUUT study (http://www.anzctr.org.au/trial_view.aspx?ID=343047): “Hysterectomy or 
Uphold Uterine Conservation in Women with Apical Prolapse – A Randomized 
Controlled Trial (HUUT). Found in the Australian and New Zealand Clinical Trials 
Registry and being performed in Victoria, Australia. This study is similar to the current 
protocol. Major inclusion criteria are stage > 2 symptomatic uterine descent. The primary 
outcome is the incidence of stage > 2 apical POP (Point C below -1 cm) at 12 and 36 
months after surgery. Secondary outcomes are overall POP stage > 2, PFDI-20 
measures, PFIQ 7 measures, PISQ 12 measures, and PGI-I measures.   
In the VAULT study, the primary outcome of anatomic and symptomatic prolapse cure is being 
assessed at one year. In the HUUT study, primary outcome time points are 12 and 36 months.  
In December of 2011, the American Urogynecologic Society (AUGS) and American Congress of 
Obstetricians and Gynecologists (ACOG) published a joint committee opinion on “Vaginal 
Placement of Synthetic Mesh for Pelvic Organ Prolapse” in which one of their recommendations 
was: “Rigorous comparative effectiveness randomized trials of synthetic mesh and native tissue 
repair and long-term follow-up are ideal.”35 Vaginal mesh is probably the most controversial 
topic in pelvic floor disorders and a strong argument can be made that the PFDN is the best 
group to study it. Our network can successfully perform non-biased rigorous, long-term 
comparative safety and efficacy studies that are needed to comprehensively assess the role of 
mesh in prolapse surgery. It is acknowledged that with this study design, we will not be able to 
separate whether it is the hysteropexy procedure itself or the mesh component of the 
hysteropexy that produces the results. 
Other Non-Trocar Mesh Hysteropexy Techniques: Currently, there are one trocar and 2 non-
trocar techniques to perform these procedures. Besides the Uphold® device, there is one other 
product that allows a non-trocar attachment to the sacrospinous ligament (AMS Elevate). The 
PFDN UCSD site has trialed both, and the disadvantage of the AMS device is that it is not as 
easily replaced for suboptimal anatomic applications, although this is a minor concern. The 
PFDN has selected the Boston Scientific Uphold® device for this study because it has been 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
7 
especially designed for uterine preservation and it is the lowest mesh load to allow this 
technique.   
Trocar Mesh Kit Techniques: Trocar-based mesh kits attempt to accomplish a similar colpopexy 
to the traditional suture suspension to the sacrospinous ligament (SSL). In this study we are 
proposing a non-trocar approach for several theoretical reasons:   
1) Trocar-based methods involve the placement of a trocar through the ischiorectal fossa, 
and the course of the trocar places the rectum at risk for perforation.   
2) Additional mesh placed in the ischiorectal fossa with trocar-based suspensions do not 
contribute to the repair and increases mesh burden without clear benefit. 
3) Direct and accurate attachment to the SSL. 
4) Surgeons in this network are comfortable with direct SSL techniques (OPTIMAL trial 
experience). It is the opinion of many investigators that trocar-based procedures for 
apical suspension will decline.  
5) There is some evidence from maker evolution that trocar kits are being replaced by non-
trocar kits.  
Hysterectomy and Vaginal Mesh Apical Suspension: This procedure is not a commonly 
performed operation. The uterus is typically left in place with these vaginal mesh apical 
techniques in an attempt to reduce the risk of mesh erosion.36 Mesh erosion rates are fivefold 
higher when hysterectomy is performed.37 Most investigators who have completed a vaginal 
hysterectomy and have easy access to the uterosacral native tissues do not see added benefit 
to adding a mesh and would rather perform a native tissue suspension.  
In conclusion, the purpose of this study is to compare vaginal hysterectomy and native tissue 
cuff suspension with a non-trocar mesh apical repair for uterine prolapse. At this point in time, 
there is no strong evidence that either uterosacral or sacrospinous ligament suspension is the 
better vaginal native tissue repair, but uterosacral ligament suspension is the most commonly 
performed operation with a vaginal hysterectomy and investigators will use that procedure for 
cuff suspension after hysterectomy. The protocol development team will monitor OPTIMAL 
study results as they become available and this recommendation is subject to change if 
sacrospinous ligament suspension is a clear winner over uterosacral ligament suspension in 
that trial. For the vaginal hysterectomy, a specific non-trocar mesh procedure will be studied, 
namely the Uphold® LITE procedure which will be performed according to manufacturer 
recommendations through an anterior transverse incision. Concomitant anterior and posterior 
colporrhaphy procedures will be allowed, as needed, per the judgment of the surgeon in both 
arms.  
B.2 
Rationale for Primary Outcome for this Study  
Over the last several years there has been increasing clarity defining success in prolapse 
surgery. The PFDN has led this effort with some important publications including “Defining 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
8 
Success After Surgery For Pelvic Organ Prolapse” by Barber et al.38 In this study using CARE 
data, the participant’s assessment of overall improvement and rating of treatment success were 
compared between surgical success and failure for each of 18 surgical success definitions 
used. The results of this study along with the emerging data on the distribution of pelvic support 
loss in the general population led the authors to conclude that success should be defined as: 
1. Absence of bulge symptoms 
2. Absence of retreatment 
3. Use of the hymen as a threshold for anatomic success.  
Further support for emphasizing the most distal measure of prolapse as the most important 
prolapse outcome measure comes from another PFDN study “Quantification of vaginal support: 
are continuous summary scores better than POPQ stage”.39 In this study, pooled baseline data 
from 322 CARE patients, 380 OPUS patients and 439 ATLAS patients were used to evaluate 
and compare 3 continuous summary support loss (SL) variables (which contained C point 
measures), POPQ ordinal stages, and SLmax (location of the single most distal point). SLmax 
demonstrated the greatest responsiveness and the best correlation with POPDI, POPIQ, PFDI 
Question 4, and PFDI Question 5. The authors recommended “Given its ability to provide an 
easily understood measure of maximum vaginal descent and its high responsiveness, SLmax 
may serve as a good primary outcome in studies evaluating prolapse treatment”. They further 
state “If the aim of a surgical procedure is to restore support to a specific compartment, it is 
logical to provide descriptive statistics for the preoperative and postoperative status of that 
compartment.”   
For this study, we considered including a measure of apical descent “point C” in the primary 
outcome, but problems with this approach include: 
1. Most importantly, for one group in this study point C is the vaginal cuff and in the other 
groups it is a cervix. The cervix typically resides on the anterior vaginal wall, is often 3 
cm in diameter, and in normal asymptomatic parous women or in hysteropexy patients, 
point C could typically be near a third or a half of -TVL while in a well-supported post 
hysterectomy cuff, point C = -TVL. An outcome measure using this point C measure of 
different anatomical structures produces an inherent bias against a group that has a 
cervix instead of a vaginal cuff.  
2. Most evidence supports that it is the most distal point that produces symptoms. If there 
is significant loss of support C, there is usually prolapse of the anterior (or posterior) wall 
more distal to that and therefore measurable in our outcome.3 
3. There are no evidence-based data at which point does “point C” become symptomatic 
when it is above the hymen.  
For all these reasons, it is important not to base the primary outcome on a C measure that will 
almost certainly be lower in the group that retains a cervix. Therefore, for this study, treatment 
success is the primary outcome and treatment success is defined as: 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
9 
1. Absence of bulge symptoms 
2. Absence of retreatment 
3. No prolapse past the hymen  
Change in point C measures, however, will be an important secondary outcome with a specific 
analysis plan and included in the primary publication.   
B.3 
Study Design – Superiority Vs. Non-Inferiority 
Discussions with the protocol committee on alternative study designs reached a consensus that 
either group could end up superior and therefore a superiority study design is most appropriate.  
RCT vs. Patient Preference Trial (PPT)  
  
A PPT trial should be considered when the study is at risk for enrolling a set of RCT participants 
that is not generalizable to the population at large. An example of this was the OPUS trial where 
there was concern that participants with some minor incontinence concerns who otherwise met 
OPUS inclusion criteria would be different than the randomized group. In this study, there are 
not any obvious patient criteria that would select out a group that would have a bias about not 
participating. Since we are confining our study to women with essentially an inactive uterus, 
strong patient concerns about uterine symptomatology that would make non-randomized 
participants different should be minimized. Therefore, we think a RCT is far preferable to a PPT 
and makes the study design cleaner. The protocol members strongly considered other designs 
including cohort studies, parallel patient preference trials, and patient preference trials if futility is 
reached in the RCT. The group considered only a RCT would provide a meaningful addition to 
the current literature on mesh and hysteropexy and Level A evidence to advance the science of 
the field. Contingency measures to improve recruiting could be considered during the trial but an 
alternative trial design contingency was not favored by the protocol group.  
B.4 
Rationale for Including a Body Image Assessment  
This study offers a unique opportunity to compare body image and sexual function changes in 
women with and without mesh, and women with and without a uterus who are treated with a 
prolapse procedure. While trials have been conducted randomizing women to removal or not of 
the cervix and have not found a difference in sexual function, there are no data regarding the 
sexual function of women who do and do not have their uterus removed. The physiologic role of 
the uterus in sexual function includes rhythmic contractions at orgasm as well as the 
psychological role the uterus may play in some women. In addition, body image changes have 
not been well-characterized in women with prolapse who then undergo treatment and body 
image has been shown by others to play a central role in sexual function. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
10 
C. 
Study Schema  
The study is a multi-center, randomized, surgical trial of women with symptomatic uterovaginal 
prolapse desiring vaginal surgical treatment. The purpose of this study is to compare a vaginal 
hysterectomy with native tissue apical repairs with a non-trocar mesh hysteropexy repair. The 
primary outcome is measured over time (up to 60 months) using a survival analysis approach.   
 A figure illustrating the study design is depicted below. 
C.1 
Study Design Diagram  
 
 
 
 
 
 
 
 
 
*All groups may receive concomitant anterior and/or posterior repairs as needed per the 
discretion of the surgeon. 
D. 
Study Population 
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 childbearing 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. This protocol 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 the 
CONSORT requirements. 
Uterovaginal Prolapse in patients 
desiring vaginal surgical repair 
Native tissue: 
TVH/USLS * 
UPHOLD hysteropexy* 
Randomized 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
11 
E. 
Inclusion and Exclusion Criteria 
Inclusion and exclusion criteria were developed to be similar to the VAULT study 
(ClinicalTrials.gov Identifier NCT01377142) so that indirect comparisons could be made 
between the arms in this study and a Laparoscopic Sacral Hysteropexy group.   
Inclusion Criteria  
 
1) Women aged 21 or older who have completed childbearing  
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 years40,41   
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 (CIN2, CIN3, or cancer))  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
12 
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  
F. 
Participant Screening 
It is anticipated that participants will come from the practices of PFDN investigators and 
advertisement will not be needed. Participants with bothersome prolapse complaints and 
prolapse at or beyond the hymen will be offered the range of therapeutic options consistent with 
the physician’s practice including but not limited to expectant management, conservative 
treatment and abdominal or vaginal surgery for their condition. Those participants desiring 
vaginal surgery will be offered participation in SUPeR. The pelvic organ prolapse quantitative 
exam and a bothersome bulge question (Question 3 of the PFDI-20) are routine clinical care 
and will be used to determine eligibility.   
Pelvic Organ Prolapse Quantification (POP-Q)  
The pelvic organ prolapse evaluation will be performed according to the guidelines established 
by the International Continence Society.10 The procedure will be standardized as demonstrated 
in a videotape produced by Duke University Medical Center (“Pelvic Organ Prolapse 
Quantification Examination”). Examinations will be performed in the dorsal lithotomy position 
with the participant straining maximally. Participants will be asked to confirm that the extent of 
prolapse demonstrated during the examination is consistent with the maximum degree of 
prolapse seen in their daily life. Standing POPQ examinations will be performed if maximal 
prolapse cannot be demonstrated in the dorsal lithotomy position. 
Pelvic Floor Distress Inventory-20 (PFDI-20) 
Participants will be considered as having bothersome vaginal bulge symptoms if they report a 
positive response to PFDI-20 Question 3 and any degree of bother (i.e., any response other 
than “not at all” to the question “How much does this bother you?”): 
a) Question 3: Do you usually have a bulge or something falling out that you can see or feel 
in your vaginal area? 
G. 
Baseline Visit 
Candidates will be approached for enrollment in a manner consistent with local IRB 
requirements and will be consented and enrolled in the study with verbal and written consent. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
13 
Once eligibility is confirmed, baseline information will be obtained which will include 
Demographics, Medical History, Physical Examination, and baseline forms. 
Demographics and Medical History  
• 
Age, race/ethnicity, marital status, education 
• 
Obstetric history (including vaginal parity) 
• 
Prior pelvic surgeries 
• 
Menopause/estrogen status 
• 
Prior treatment of pelvic organ prolapse or urinary incontinence  
• 
Smoking 
• 
Diabetes 
• 
Urinary tract infection history 
• 
Current medication use  
Physical Examination  
• 
Height and weight 
Surgery should be scheduled and performed within 4 months. If more than 4 months transpires 
before surgery, baseline instruments will need to be re-administered.  
H. 
Randomization 
After eligibility is determined and consent is obtained from the participant, the participant will be 
randomized to one of the two treatment arms using a web-based randomization system. To 
minimize any risk of selection bias resulting from clinician knowledge of current or future 
treatment assignments, each participant will be randomized by the surgeon when the participant 
is in the operating room. The participant will be randomized to one of two apical procedures: 
either a vaginal hysterectomy with USLS or mesh strap vaginal hysteropexy (Uphold® 
procedure), with the randomized procedure provided to the surgeon for each participant 
individually in the operating room immediately prior to the surgery. Other native tissue vaginal 
wall prolapse repairs (e.g., anterior colporrhaphy, posterior colporrhaphy, perineorrhaphy) will 
be allowed as needed.  
Randomization (1:1 to the two treatment arms) will be performed using permuted blocks, with a 
block size that is known only to the DCC and will be stratified by site. For each participant, the 
web-based system will determine the treatment allocation from a static randomization table 
developed by the study randomization statistician prior to the start of the study. Only the study 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
14 
statistician and randomization system programmer will have access to the randomization table 
to minimize the risk of selection bias. 
I. 
Appointment Scheduling 
Routine clinical practice postoperative visits will take place during the 12 week postoperative 
period with the inclusion of one study visit at 6 weeks to assess for early outcomes. The 6 week 
in person visit and the in person visits every 6 months for the duration of the study will capture 
the following outcomes: 
1) Urinary function including duration of post-op catheterization and de novo voiding 
dysfunction rates. A PVR will be assessed by catheterization or bladder scan at the 6 
week visit and this is defined as an elevated postoperative post void residual > 150 ml 
that was not present preoperatively.    
2) De novo incontinence rates and severity assessed by the UDI-6, ISI, and AE survey  
3) Functional activity by administration of the Functional Activity Assessment Scale42 
4) Mesh-related complications: mesh exposure in the vagina or mesh erosion into another 
organ and the classification of the intervention: 
a) None or non-surgical medical intervention only 
b) Minor or intra-office surgical intervention 
c) Outpatient surgery 
d) Inpatient surgery 
5) Rates, location, and severity of pelvic pain using the modified Surgical Pain Scale that 
has demonstrated validity and responsiveness in OPTIMAL43, pain medication use, AE 
survey,  and Pain Mapping Instrument 
6) Pelvic infection: 
a) Perioperative infections, defined as requiring antibiotics  
b) Urinary tract infections, defined as culture proven or antibiotics given  
c) Vaginal infections with flora uncommon to the vaginal canal 
7) Neuromuscular problems (including groin and leg pain) with the use of the Pain Mapping 
Instrument 
8) Vaginal scarring, vaginal shortening, de novo dyspareunia, and worsening dyspareunia 
with AE survey  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
15 
Subsequent study visits will then occur at 6 month intervals for up to 60 months for collection of 
all study measures.   
J. 
Interventions – Surgical Interventions 
J.1 
Surgeon Experience and Certification 
 
Experience  
To reduce bias related to surgical experience, surgeons should be experienced with all 
procedures being performed in this study. For the native tissue arm in this study, surgeons need 
to be experienced with vaginal hysterectomy and uterosacral ligament suspension and for the 
uterovaginal Uphold® procedures, surgeons need to be experienced with the Uphold® 
procedure.  
In this study, all participating surgeons should be qualified to do either procedure and will 
require certification to be a study surgeon. Because vaginal hysterectomies and uterosacral 
ligament suspension procedures have been performed for decades, while Uphold® procedures 
are less than 4 years old, it is acknowledged that most surgeons in this study will have more 
experience with the TVH/USLS arm. However, the primary skills required to do the Uphold® 
procedure (e.g., anterior vaginal dissection to the sacrospinous ligament and the use of a Capio 
device) are familiar to urogynecologic surgeons and experience with these techniques is 
transferrable to the Uphold® procedure. Certification criteria ensure that all study surgeries are 
performed by surgeons who are well trained on procedures for both arms to assure study 
validity, while at the same time establishing standards for the trial that allow results to be 
generalized to the population of urogynecologic surgeons likely to perform these surgeries in the 
future.   
Certification    
All surgeries will be performed by certified surgeons. Surgeon certification will require an 
attestation by the surgeon and signed off by the site PI and it will require the following 
requirements. 
FOR TVH/USLS CERTIFICATION: 
1. All surgeons will view a surgical videotape or DVD illustrating essential components of 
the uterosacral vault suspension technique.    
2. All certified surgeons should have performed a minimum of 20 vaginal hysterectomies, 
20 uterosacral procedures, with performance of at least 5 of these apical procedures in 
the 12 months prior to beginning participant enrollment. 
FOR UPHOLD® CERTIFICATION 
1. All surgeons will view a surgical videotape or DVD illustrating essential components of 
the Uphold® technique.  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
16 
2. All certified surgeons should have performed 20 sacrospinous ligament dissections in 
their careers, with performance of at least 10 anterior vaginal dissections to the 
sacrospinous ligament.  
3. Performance of at least 10 Capio suture applications.  
4. Performance of or has received hands-on proctoring on at least 5 Uphold® procedures 
for uterovaginal prolapse or cuff-vaginal prolapse. Surgeons who meet all the criteria 
except the Uphold® procedure experience criteria may enroll participants in the SUPeR 
study; however, if the participant randomizes to the Uphold arm, the surgery will be 
proctored by a certified study surgeon. This certified surgeon will be scrubbed in and 
provide hands on supervision for the anterior dissection, Capio placement of the mesh 
arms, tensioning parts of the procedure, and incision closure. The certified proctoring 
surgeon will be the study surgeon of record and takes full responsibility for the 
performance and the quality of the procedure. The procedure may be counted as a 
proctored procedure for the other surgeon.  
5. Prior to signing off on certification for each site’s surgeon, the site PI will review these 5 
cases for any Uphold® procedure related complications and may request additional 
proctoring or experience before approving certification of that surgeon. 
Surgical Education and Monitoring  
At baseline, all study surgeons will provide data on their training, surgical volume, and length of 
time in practice. On a quarterly basis, all study surgeons will provide the number of uterovaginal 
apical suspensions that they performed outside of the SUPeR study. The surgical videotapes or 
DVD’s illustrating essential components of the uterosacral vault suspension technique and 
Uphold® technique will be made available and distributed to each participating surgeon, along 
with a detailed written description of the technique and guidelines for concurrent procedures. 
The videotape/DVD and written material will be reviewed and discussed at an in-person PFDN 
Steering Committee meeting at a time shortly before enrollment begins. Each Principal 
Investigator at the clinical sites will be responsible for reviewing and discussing the videotape 
and written materials with participating surgeons at his/her site (before enrollment begins). 
Certified Surgeons as Teachers 
All sites in the Pelvic Floor Disorders Network are teaching institutions and have accredited 
fellowship programs in Female Pelvic Medicine and Reconstructive Surgery. Residents and 
fellows may assist at surgery for SUPeR participants. The certified surgeon is always the 
surgeon of record for the study and takes full responsibility for the performance and the quality 
of the procedure. The certified surgeon will be scrubbed in and will perform (or provide hands-
on supervision) of the procedure. The certified surgeon assumes full responsibility for assuring 
proper uterosacral ligament suture placement, attachment of these sutures to the vagina, 
anterior dissection for the Uphold® procedure, Capio placement of the mesh arms, tensioning 
parts of either procedure, and incision closure.    

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
17 
J.2 
Description of Surgical Procedures 
Uterosacral Ligament Suspension (ULS) 
The ULS procedure used in this protocol is a modification of the technique described by Shull.13 
1. ULS is performed through a vaginal incision.   
2. The placement of uterosacral ligament stitches will be performed in such a way as to 
avoid neurovascular and ureteral compromise. 
3. One permanent and one delayed absorbable 0 or 2-0 monofilament suture (2 sutures 
per side; 4 sutures total) must be placed in each ligament, extending to the ipsilateral 
anterior and posterior fibromuscular wall of the vaginal apex. The permanent sutures will 
be placed near full thickness, excluding vaginal epithelium. The delayed absorbable 
sutures will be placed full thickness through the vaginal wall with the knot tied inside the 
vaginal canal. The type of suture material will be recorded.   
4. The use of a pulley stitch is allowed.   
5. No plication of the uterosacral ligaments across the midline or culdoplasty is allowed. 
6. Other aspects of the suspension procedure will be left to surgeon preference but will be 
recorded.  
7. In the event that clinical circumstances prohibit safe/effective completion of the planned 
procedure, the preferred back-up procedure is a SSLF. In the unlikely event that both 
ULS and SSLF cannot be performed safely or effectively, the choice of vaginal 
suspension procedure will be left to the surgeon's discretion and recorded. 
Uphold® Procedure  
The Uphold® procedure used in this protocol is a modification of the technique described by Vu 
and Goldberg.32  
1. Hydrodissection of the vaginal walls will be performed with at least 30 cc of 0.25% 
bupivacaine with epinephrine or dilute Pitressin (20 Units/50-100 cc).  
2. An approximate 4 cm transverse vaginal incision is made in the anterior vagina wall 
between the bladder neck and the cervix but at least 3 cm from the cervix so that the 
suture line will not overlap with the mesh.  
3. Blunt or sharp dissection to approach the sacrospinous ligament extraperitoneally. 
4. After confirmation of the location of the ischial spine, the tapered lead and mesh 
assembly will be delivered into the SSL 1-2 fingerbreadths medial to the ischial spine.  
5. The most cephalic edge of the mesh will be attached to the cervix with sutures. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
18 
6. Mesh modifications (e.g. cutting) are strongly discouraged; any exceptions will be 
documented on operative case report forms.   
7. Tensioning to re-suspend the apex without tense mesh arms. 
8. Vaginal closure with 2-0 polyglactin. 
9. Placement of a vaginal pack and Foley catheter removed on POD1.   
For all procedures: 
1. The study surgeon is responsible for meeting the experience requirements, is the 
surgeon of record, and will be present and scrubbed in for key portions of the procedure. 
Residents or fellows may participate in procedures as is standard for each Clinical Site. 
2. Cystoscopy with intravenous indigo carmine dye (or an appropriate substitute) 
performed at the end of the procedure after all vault suspension sutures are tied or after 
the Uphold® straps are adjusted and is required as a standard part of the surgical 
procedure. 
3. Prophylaxis against deep vein thrombosis is required for all participants. The method 
may be chosen by each surgeon. 
4. Preoperative intravenous antibiotic prophylaxis is required as part of the surgical 
procedure. The details (choice of antibiotic, dose, etc.) will be determined by each 
surgeon. 
5. All concomitant native tissue procedures must be declared and recorded prior to 
randomization. The surgeon has the discretion to alter from this preoperative plan as 
necessary to achieve the desired anatomic result. Any such alterations must be 
recorded. 
6. Anterior and posterior colporrhaphies will be performed at the discretion of the operating 
surgeon such that points Aa, Ba, Ap and Bp are less than or equal to -1 cm at the end of 
the procedure (i.e., anterior and posterior vaginal points located at least 1 cm above the 
hymen) at the end of the procedure. Colporrhaphies, when performed, will be performed 
with 2-0 or 0 delayed absorbable sutures. A non-straining POPQ examination will be 
performed and recorded at the end of the operative procedure and prior to cessation of 
anesthesia. 
Surgery for Stress Urinary Incontinence     
Stress continence outcomes are not a primary outcome in this study, and it is recognized that 
there is evidence to support universal or selective use of midurethral slings in the setting of 
vaginal operations for prolapse. Therefore, concomitant full length transobturator or retropubic 
midurethral slings will be allowed per the discretion of the surgeon. The placement of a 
midurethral sling should not have an effect on the primary outcome because tension-free 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
19 
vaginal tape has been shown to not provide additional distal anterior vaginal wall support for 
patients undergoing total mesh colpopexy or laparoscopic colpopexy.44,45   
J.3 
Masking of Randomized Intervention 
Although the primary outcome does not depend on masked patients and blinded evaluators, 
several important patient-reported secondary aims are subject to patient reporting bias if the 
participant is aware of her group assignment. For example, in this current era of television 
advertisements recruiting patients for class action law suits against mesh manufacturers, many 
urinary, bowel, and sexual complaints are being attributed to transvaginal mesh and it is quite 
possible that if the participant knows that she has mesh she might be more likely to over-report 
these conditions. There are also significant internet testimonials that hysterectomy worsens 
sexual function and a patient’s knowledge of having or not having a uterus could bias her 
reports on sexual function. For all these reasons, the ideal study design encourages masking 
and blinding to treatment assignment. There is precedent for achievable patient and evaluator 
blinding in RCT’s of supracervical and total hysterectomies46 and in this study, where the uterus 
is inactive, we think those successful blinding examples are relevant to this study design.  
The study surgeon is providing clinical care to enrolled participants, thus masking the surgeon 
to treatment allocation or participant symptoms is not practical or feasible, other than the 
allocation concealment prior to surgical randomization. The study surgeon will not be performing 
the anatomic outcome assessments. It is our intent that when feasible and ethical, all outcomes 
assessors and the participant will be masked to the treatment allocation. All participants will be 
asked to remain masked to their treatment group for the duration of the study, although we 
recognize that unintentional unmasking by the participant may occur.  Current ACOG 
recommendations allow women age 30 years or older with known recent negative cervical 
cytology and negative HPV testing to be screened no sooner than 3 years.40  Current US 
Preventative Services Task Force, American Cancer Society, American Society for Colposcopy 
and Cervical Pathology, and American Society for Clinical Pathology recommendations allow no 
screening for age <21, every 3 year screening for ages 21-29, every 5 year screening ages 30-
65, and no screening for women older than 65.41 Therefore all participants in this study should 
be able to go 3 years without screening and the overwhelming majority of participants in this 
study will be >30 and are allowed to have every 5 year screening.   Unmasking is permitted for 
the rare amenorrhoeic woman with a uterus aged 18-30 eligible for this study who in the opinion 
of the study surgeon needs screening during the study. We recognize that this masking is for 
cervical cancer screening and women may still have regular exams. In the event the patient is 
about to have a pelvic exam or imaging study of her pelvis we will request the patient to remind 
her provider to not tell her about the status of the absence or presence of her uterus. 
Participants will be encouraged to see the study team for any gynecologic problems or 
evaluations during the course of the study. At every 6 month visit, the participants will be 
queried if they are still blinded, and if not, what caused the unblinding and what group they think 
they are in? This will be done in a manner that reaffirms that blinding is preferred for the 
duration of the study. After the study is completed (maximum 60 months) participants will be 
queried as to what randomization arm they think they received and will then be notified of their 
uterine and mesh status. To minimize biases, subjective and most objective outcomes will be 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
20 
obtained by study nurses or coordinators masked to the procedure. POPQ measures will be 
obtained by co-investigators or different study nurses who will not be blinded to the surgical 
procedure because they will either see or not see a cervix but would be less biased than the 
operating surgeon towards over-reporting the anatomic surgical outcome. 
Table 3. Masking Summary 
Masking 
Uterovaginal Prolapse Intervention 
Participant  
Yes 
Study coordinator or study nurse 
Yes 
Telephone interviewer (if applicable)  
Yes 
Study surgeon 
No 
Anatomic evaluator# 
No# 
# to maximize masking, it is proposed that the anatomic evaluator not be the study coordinator or study 
nurse who should remain masked. The anatomic evaluator should be a Co-investigator, fellow, or other 
qualified nurse who did not perform the surgery.  
It is preferable to maintain masking of group assignment for participants until the study 
completion. There are two issues to consider: (1) masking the participant to the surgical 
intervention throughout study follow-up unless there are medical reasons or participant 
insistence to reveal assignment; and (2) masking the research staff (evaluators) who will be 
performing data collection for outcome measures. In addition to those described above, the 
following steps will be taken to maintain masking while maintaining participant safety: 
• 
For the dictated operative note, the procedure listed under the “Procedure” heading will 
be indicated as “vaginal apical suspension as per SUPeR protocol.” The specific type of 
vault suspension will not be listed under the “Procedure” heading; however, details of the 
vaginal hysterectomy / vault suspension or hysteropexy will be described in the text of 
the detailed operative description.   
• 
For sites with electronic medical records, all references to the vaginal apical suspension 
procedure will be indicated as “vaginal apical suspension as per SUPeR protocol” with 
the exception of the detailed operative description in the text of the dictated operative 
note described above. 
• 
For the handwritten operative note in the participant’s hospital chart (if applicable), the 
procedure will be indicated as “vaginal apical suspension as per SUPeR protocol (see 
dictated operative note)”. 
• 
The procedure on the surgical consent form (not the research consent form) will be listed 
as “vaginal apical suspension per SUPeR protocol.” 
• 
The study surgeon (not the study coordinator or other research staff that will be 
completing postoperative data collection) will complete the intra-operative portion of the 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
21 
Hospitalization Form which will be transmitted electronically to the Data Coordinating 
Center. 
• 
A sticker will be placed on the participant’s hospital chart, indicating that she is enrolled 
in the SUPeR study and that the exact type of procedures performed should not be 
revealed to her. 
• 
In the case the care team needs to know the exact surgical procedure, details of the 
surgery can be found in the procedure details of the operative note.  
• 
Key clinical and laboratory costs that have the potential to unmask the participant 
through the billing process will be covered by the research study.  
If unmasking does occur, the study coordinator will complete a protocol deviation form.  
Deviations will be tracked and reported to the DSMB to determine if unmasking is occurring at 
high frequency and to determine if a pattern of unmasking can be found and addressed by 
protocol or policy revisions.  
K. 
Outcome Visits 
Outcome visits will occur every 6 months up to a maximum of 60 months. All women will 
continue to be followed through the end of the study, including those who seek alternative 
treatment or re-treatment to ensure that all safety events are captured. At each of these visits, a 
physical exam will be performed to assess anatomic (POP-Q) results and also to evaluate for 
mesh exposures and erosions and to ask about bulge symptoms (PFDI-Q3) and retreatment so 
that the primary outcome and safety outcomes will be assessed. The PFDI-Q3 has been 
demonstrated to function well as a standalone question and does not require the entire PFDI-20 
to be administered with it.47 Additionally at 6, 12, 24, 36, 48, and 60 months secondary outcome 
measures will be administered.  
L. 
Timeline of Visits/Calls and Study Schedule 
In-person visits every 6 months up to 60 months. It is not anticipated that with this frequency of 
in person visits there will be a need for telephone calls. Total study enrollment time is estimated 
to be 24 months. Based on these assumptions, an expected study schedule is included in 
Appendix B.  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
22 
Table 4. Timeline of Measures  
Measure 
Base-
line 
Peri-
op 
6 
wks 
6 
mo 
12 
mo 
18 
mo 
24 
mo 
30 
mo 
36 
mo 
42 
mo 
48 
mo 
54 
mo 
60 
mo 
Demographic 
info 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Operative and 
perioperative 
review * 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Postoperative 
recovery#  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
POPQ  
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE review  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exam for 
mesh 
exposure  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PFDI –
Question 3 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Functional 
Activity Scale 
X 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
Surgical Pain 
Scale 
X 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
PFDI-20 
(includes 
POPDI-6, 
CRADI-8, 
UDI-6) 
X 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
PFIQ 
X 
 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
PGI-I  
 
 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
ISI 
X 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
PISQ-IR 
X 
 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
BIS 
X 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
SF-12  
X 
 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
* Includes OR complications with Dindo score, EBL, Transfusion, HGB change from pre-op to POD1, 
length of hospital stay. 
# Assess duration of postoperative catheterization, PVR, de novo incontinence, pelvic pain scale and pain 
mapping review for vagina, groin, and leg pain.    
M. 
Outcome Measures 
The following outcome measures will be collected at baseline, 6 months, 12 months, and then 
every 6 months with the survival analysis approach.   
M.1 
Primary Outcome Measure   
A participant will be considered a treatment failure if any ONE of the following criteria is met:  
1) Report of bothersome vaginal bulge symptoms (see definition below), or  
2) Re-treatment for prolapse (surgery or pessary), or  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
23 
3) Any prolapse measure (Ba, C, Bp) is beyond the hymen (i.e. > 0 cm) 
Bothersome vaginal bulge symptoms = positive response to Question 3 of the PFDI-20: “Do you 
usually have a bulge or something falling out that you can see or feel in your vaginal area?” 
AND any degree of bother. This single question has been identified to most accurately and 
reliably identify those women with POP. An affirmative answer to this question was 96% 
sensitive (95%CI 92-100) and 79% specific (95%CI 77-92) for prolapse beyond the hymen. The 
1-week test-retest reliability was good (kappa .84).47 
 
Participants not considered a treatment failure for the primary outcome will be considered a 
treatment success.  
M.2 
Comparative Secondary Outcome Measures 
Secondary Aim 1 – Secondary Efficacy Outcomes: These measures will require a statistical 
analysis plan and will be reported in the primary outcome manuscript.  
1) Anatomic: POPQ point (Ba, Bp, C), mean or median (but should be normally distributed) 
measures postop in each group. Proportion of participants in each group with C > -1/2 
TVL.  
2) Functional: 
a) Prolapse – mean Patients Global Impression of Improvement (PGI-I)48,  mean 
overall prolapse symptoms using POPDI-649 scores   
b) Urinary – urinary function including duration of post-op catheterization, mean UDI-6 
scores49, Hunskaar Incontinence Severity Index, de novo voiding dysfunction rates, 
de novo incontinence rates 
(i) Sexual – mean PISQ-IR50 and specific rates of de novo dyspareunia 
(ii) Bowel – bowel function using CRADI-8 scores49  
(iii) QOL – general SF-12 scores and sub-scales51, and Pelvic QOL mean PFIQ 
score49; Functional Activity Assessment Scale42 
Secondary Aim 2 – Safety: These measures will require a statistical analysis plan and will be 
reported in the primary outcome manuscript.  
1) Intraoperative safety – group comparisons of mean Operative time, estimated blood 
loss, blood transfusion, intra- and post-operative complications categorized using a 
modification of the Dindo Classification.52 
2) Adverse events – mesh related complications: mesh exposure in the vagina or mesh 
erosion into another organ and the classification of the intervention: 
a) none or non-surgical medical intervention only 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
24 
b) minor or intra-office surgical intervention 
c) outpatient surgery 
d) inpatient surgery 
Other complications possible in both arms:  
1) Rates of pain captured from the modified Surgical Pain Scale43,  pain medication use, 
and location of pain with Pain Mapping Instrument 
2) Pelvic infection: 
a) perioperative infections 
b) urinary tract infections 
c) vaginal infections with flora uncommon to the vaginal canal 
3) Vaginal shortening, de novo vaginal bleeding, atypical vaginal discharge, fistula 
formation, neuromuscular problems (including groin and leg pain)  
4) Need for subsequent procedures – any surgical or non-surgical treatment for pelvic floor 
disorders (including urinary incontinence, voiding dysfunction, defecatory dysfunction or 
fecal incontinence, recurrent prolapse, and dyspareunia/pelvic pain). Any subsequent 
uterine or cervical office or Operating Room procedure in hysteropexy group (e.g., 
cervical biopsy, LEEP, hysteroscopy, D and C, hysterectomy).  
5) Subsequent uterine or cervical pathology 
6) Rates of vaginal scarring defined as de novo vaginal scar requiring medical or surgical 
intervention or adversely affecting quality of life 
7) Rates of vaginal shortening, de novo dyspareunia, and worsening dyspareunia with AE 
survey instrument 
Complication Monitoring 
Groups will be compared for rates of “important complications”. The definition of “important 
complication” is:  
• 
Any Grade IIIb or greater Dindo complication, which will also include any intervention 
under a regional anesthetic. These concurrent or subsequent Operating Room 
interventions include but are not limited to: mesh removal, ureteral repair, abscess 
drainage, revision of vaginal stricture, operative hysteroscopy, or hysterectomy.   
• 
New onset (de novo) dyspareunia preventing vaginal intercourse. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
25 
• 
Intractable pelvic pain – defined as daily pelvic pain after the 6 week postoperative visit 
which significantly affects the participant’s quality of life requiring ongoing management 
or is refractory to medical and physical therapy.  
The important complication rate will be calculated at 6 month intervals for both groups; as a 
guideline, the protocol committee considers that a true difference of more than 15 percentage 
points in the complication rates for the two surgical procedures to represent an important 
difference between groups. Stopping the study will be considered by the DSMB during their 
regularly scheduled reviews if they find compelling evidence of an important difference based on 
point and interval estimates of the important complication rates in the two study arms. While the 
true difference of 15 percentage points or greater can guide the DSMB considerations, final 
decisions about a magnitude of difference in safety risk that warrants a recommendation to stop 
the study lie fully within the discretion of the DSMB.  
Secondary Aim 3 – Predictors of Poor Outcomes: The co-variates of advanced prolapse, 
age, obesity, smoking, menopausal status, estrogens, primary vs. recurrent prolapse, and 
physical and functional activity as measured by the Functional Activity Scale will be evaluated to 
determine if they predict higher treatment failure.  
Secondary Aim 4 – Cost-Effectiveness Analysis: The cost-effectiveness analysis will be 
conducted from a payer perspective and will be expressed as incremental cost required to 
produce one additional unit of quality-adjusted life year (QALY). Data on each participant’s use 
of medical and non-medical resources related to urologic or gynecologic conditions will be 
collected during the follow up period. Direct and indirect costs of the treatment of apical pelvic 
organ prolapse with native tissue surgical repair or transvaginal mesh repair and women’s 
preference for health states for improvement in pelvic organ prolapse will be estimated.  
We plan to capture incremental health care resource use related to study interventions and 
complications and other prolapse management (such as pessary use or additional surgery). 
Costs will be estimated using the resource costing method where medical service use from 
each study case report form is monetized by multiplying the number of units of each medical 
service by the average unit cost of this service in dollars. This method allows a consistent 
capture of resource use when costs are incurred across multiple health systems or payers. 
Detailed case report forms that include the procedures performed (e.g. surgical interventions) 
and clinical events (e.g. complications, readmissions) will be completed by the study coordinator 
at study visits. Data from three resource types (physician visits, hospital procedures and 
admissions, and emergency room visits) will be collected. Cost for each medical service use will 
be assigned based on national Medicare reimbursement rates, as indicated in the following 
table. Additionally, we will obtain detailed billing records for a limited number of procedures and 
hospitalizations in selected study sites (e.g. prolonged admission to the ICU or readmission to 
the hospital for a surgical complication). 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
26 
Table 5. Resource Utilization Data Collection and Price Data Source, by Utilization 
Category  
Service  
Price Weight  
Physician visit  
Medicare reimbursement  
Surgical intervention and admission 
Complication hospitalization – routine   
Medicare reimbursement 
Medicare reimbursement  
Complication hospitalization – significant 
ER – routine complication 
Billing record – actual amount paid  
Medicare reimbursement 
ER – significant complication  
Billing record – actual amount paid  
Subsequent surgery  
Medicare reimbursement  
The SF-6D preference-based utility index algorithm derived from the SF-12 instrument53 will be 
used to calculate each participant’s utility index at baseline and various follow up time points 
based on her responses to the SF-12 questionnaire. The SF-6D focuses on seven of the eight 
health domains covered by the SF-12: physical functioning, role participation (combined role-
physical and role-emotional), social functioning, bodily pain, mental health, and vitality). This 
instrument has been previously used in women with urinary incontinence.54 These data will be 
used to compare change in QALYs between the two treatment groups. We are choosing to use 
a general scale to calculate change in utilities (rather than condition-specific) to allow for 
comparison of cost-effectiveness results with other interventions and diseases. Because the 
follow up period for participants spans at least three years, costs and QALYs in the second year 
and third year of follow up will be discounted using a 3% discount rate/year.  
Differential mean costs and differential mean QALYs between the two treatment groups will be 
estimated using multiple regression analysis. Specifically, a generalized linear model with 
appropriate link function (e.g., log-link) and response probability distribution (e.g., gamma 
distribution) will be used to analyze costs due to the potential skewness and heteroscedasticity 
of medical expenditure data, while an ordinary least squares regression will be used for 
analyzing QALY data. The models will account for treatment group, study site and stratification 
factors, as well as other characteristics of the participants that are found to differ significantly 
between the traditional vaginal hysterectomy with native tissue vault suspension and mesh 
hysteropexy suspension groups. When estimating QALYs, we will also adjust for participants’ 
baseline utility scores to account for potential imbalance in baseline utility between the two 
treatment groups.55 
We will calculate the incremental cost-effectiveness ratio (ICER), which is the differential mean 
costs divided by the differential mean QALYs between the two groups, to assess the additional 
costs associated with each additional QALY gained. Our base case analysis will be conducted 
based on participants with complete data. Sensitivity analysis will be conducted to include 
participants with incomplete data using the multiple imputation method. Non-parametric 
bootstrapping resampling technique will be used to derive the 95% confidence interval for the 
ICER.56, 57 In addition, cost-effectiveness acceptability curve (CEAC) will be generated to 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
27 
illustrate the likelihood that one treatment is more cost-effective than the other with various 
ceiling cost-effectiveness ratios.  
In the case that a statistically significant difference in changes in utilities (as measured by SF-
6D) between the treatment groups is not detected, we plan to conduct supplemental analyses 
using alternative outcome measures, such as incremental cost per treatment success, 
incremental cost per POP HRQOL, or incremental cost per satisfaction.  
The cost-effectiveness evaluations will be conducted as within-trial comparisons. A decision 
analytic model will also be developed from trial data to evaluate the trajectory of the cost-
effectiveness ratio over a lifetime; assuming an average life expectancy, given the average age 
of participants at the time of the intervention. 
Secondary Aim 5 – Body Image: We will compare BIS scores between women who undergo 
uterovaginal prolapse repair with a mesh hysteropexy and with hysterectomy and native tissue 
repair. 
Hypothesis: Women with uterovaginal prolapse will demonstrate improvement in body image 
as measured by a body image scale following surgery for uterovaginal prolapse, and will parallel 
changes in sexual function; both measures will improve with improvements in prolapse, as 
measured by the leading edge of prolapse and the POPDI. 
Hypothesis: BIS scores will demonstrate greater improvement in the cohort of SUPeR women 
who undergo hysteropexy with mesh.  
Background: Body Image is how a woman feels—her perceptions and attitudes—about her 
body.58 Body image likely plays an important role in demand for treatment for pelvic organ 
prolapse and a woman’s satisfaction with treatment. The Body Image Scale (BIS) was originally 
developed and validated to measure changes in body image in women treated for breast 
cancer.59 Jelovsek et al modified the BIS and compared women with advanced prolapse (stages 
3 and 4) to a cohort of women with normal support (stages 0 and 1). In that cross sectional 
cohort study, women with prolapse were more likely to be self-conscious about their body, less 
likely to feel physically attractive, less likely to feel feminine, and less likely to feel sexually 
attractive.60 In addition, women with decreased body image also scored more poorly on the 
physical scale of the SF-12, a general measure of overall quality of life.61 Further investigations 
have explored the interplay between body image, sexual function and prolapse in a large multi-
center cohort study of 384 women undergoing surgical and non-surgical treatment for 
prolapse.60, 62 At baseline, women with poorer body image reported poorer sexual function.  Of 
the 235 women who gave data at 6 months follow-up, sexual function improved (PISQ 12 pre 33 
+/- 0.6 vs. post 43 +/- 0.8, p < .0001) as well as changes in body image (pre 23.2 +/ 6 vs. post 
12.8 +/- 3, p < .001) and bother from prolapse (POPDI-6 40.6 +/- 1.7 versus 14 +/- 1, p < .01). In 
a multivariate linear regression analysis, only changes in body image and body mass index 
remained associated with changes in sexual function.60    
Using the Body Exposure During Sexual Activity Questionnaire (BESAQ) and the Body Image 
Quality of Life Inventory (BIQLI), Lowder et al compared cohort of 76 women planning surgery 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
28 
for prolapse to 67 women controls with normal vaginal support.63 BESAQ scores improved after 
surgery, as did measures of prolapse and sexual function on the PISQ 12; in a regression 
analysis, postoperative changes in POPDI scores were predictive of 6 month BESAQ scores, 
further demonstrating the association between prolapse and body image changes. In a follow-
up qualitative study of 25 women who participated in focus groups and 27 women who 
participated in one-on-one interviews, women with prolapse reported they felt self-conscious, 
less feminine and less attractive. In addition, women reported that they often changed sexual 
intimacy practices because of their prolapse, or avoided intimacy altogether.64   
While the PFDN has described changes in sexual function in women undergoing treatment for 
prolapse and following childbirth, these evaluations of sexual health has focused on changes in  
validated sexual function measures (either the PISQ 12 or the Personal Experiences 
Questionnaire) and change in sexual activity status and did not include measures of body image 
changes. SUPeR will randomize women to either a vaginal apical repair with mesh or a vaginal 
native tissue repair to answer the question of whether mesh augmented repair without 
hysterectomy leads to better prolapse outcomes than native tissue repair with hysterectomy for 
treatment of uterovaginal prolapse. This trial offers a unique opportunity to explore the body 
image changes of women following vaginal surgery for uterovaginal prolapse with and without a 
graft-augmented repair and to evaluate whether body image changes play a role in reports of 
sexual function following repair. Additionally, we will be able to add to the literature regarding 
the possible impact of hysterectomy on body image.   
Methods: The original BIS was developed in 276 patients diagnosed with cancer and then was 
revised and further validated in a cohort of 682 women with breast cancer. Factor analysis of 
this measure revealed a scale that was resolved with a single factor that accounted for > 50% of 
variance in responses. The scale showed high reliability (total Cronbach’s alpha 0.93), criterion 
and discriminant validity.58 The original BIS included two questions which were eliminated by 
Jelovsek (“Have you been feeling the treatment has left your body less whole?” and “Have you 
been dissatisfied with the appearance of your scar?”) and was reworded to be specific to 
prolapse (Table 6); this modified version was used in both the papers by Lowenstein. Others 
have used the BIS scale in a cohort of women undergoing treatment for prolapse with a 
pessary, and included one of the previously eliminated questions, “Have you been feeling the 
treatment has left your body less whole?”65 but eliminated the item regarding the appearance of 
a scar. We propose to use the original BIS scale of 10 items, with the change in wording to 
make the scale specific to prolapse proposed by Jelovsek. The BIS scale will be administered at 
baseline, 6 months, 12 months, and then every 6 months until the study is concluded. 
Total BIS scores will be calculated as described by Hopwood et al, and changes in BIS scores 
will be correlated with changes in PISQ R scores, the leading edge of prolapse, and POPDI 
scores using Pearson’s and Spearman correlation coefficients. If measures are correlated, we 
will further describe changes in individual items of the BIS scale before and after treatment for 
prolapse, to determine which portions of the BIS scale explain the overall change in BIS scores, 
and evaluate the associations between BIS item scores and PISQ-IR item scores. General 
linear model analyses will be used to evaluate how well the combination of BIS scores, 
demographic and experimental variables explain changes in PISQ-IR scores. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
29 
Between randomization group comparisons will also be made using linear models for total and 
item scores controlling for randomization strata. We will also utilize extensions of this model to 
evaluate if any differences in BIS scores are either modified by or confounded with differences 
in either efficacy or side effects.  
SUPeR will recruit 180 women. Body image will be measured in all women enrolled even 
though not all women will be sexually active. For the analyses described above, we anticipate 
that approximately 75% (135 women) will report sexual activity, and approximately half of the 
cohort will be randomized to the group undergoing mesh strap/uterine preservation or native 
tissue repair with hysterectomy. Lowenstein et al demonstrated a change in BIS scores before 
and after treatment for prolapse in sexually active women from 23.2 +/- 1.6 to 12.8 +/- 1.3 in a 
cohort of 239 women undergoing both surgical and non-surgical treatment for prolapse. 
Because all women in this study will undergo surgical procedures, we anticipate that differences 
in this study will be at least this large; consequently, assuming that approximately 130 women 
are sexually active, the study will have at least 90% power to detect those changes.  
Table 6. Body Image Scales 
# 
Original Body Image Scale (BIS) 
Modified Body Image Scale (MBIS) 
1 
Have you been feeling self-conscious about your 
appearance? 
Same 
2 
Have you felt less physically attractive as a 
result of your disease or treatment? 
Have you felt less physically 
attractive as a result of your vaginal 
prolapse? 
3 
Have you been dissatisfied with your 
appearance when dressed? 
Same 
4 
Have you been feeling less feminine as a result 
of your disease or treatment? 
Have you been feeling less feminine 
as a result of your vaginal 
prolapse? 
5 
Did you find it difficult to look at yourself naked? 
Same 
6 
Have you been feeling less sexually attractive as 
a result of your disease or treatment? 
Have you been feeling less sexually 
attractive as a result of your vaginal 
prolapse? 
7 
Did you avoid people because of the way you 
felt about your appearance? 
Same 
8 
Have you been feeling the treatment has left 
your body less whole? 
Deleted 
9 
Have you felt dissatisfied with your body? 
Same 
10 
Have you been dissatisfied with the appearance 
of your scar? 
Deleted 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
30 
N. 
Sample Size/Power Calculations  
This study is designed to compare the relative effectiveness of two transvaginal apical 
suspension strategies for uterovaginal prolapse: a mesh augmented hysteropexy vs. vaginal 
hysterectomy and uterosacral ligament suspension. Power and sample size calculations were 
generated to determine the sample size needed to test for treatment difference favoring the 
mesh augmented strategy (i.e., a superiority trial) across the study arms for a variety of 
assumptions about effect size and study follow-up time. For all power analyses, we assumed 
that failure in both arms follows an exponential survival model and that the native tissue repair 
has a success rate of 80% at 24 months. This 80% calculation is based on an assumed 85% 
anatomic success rate for uterosacral ligament suspension (Table 2) and an additional 5% 
failure rate based on symptom failure. In the only published Uphold® series there is a 98% 12 
month anatomic success rate.32 Although no 2-year outcome data are available for the Uphold® 
procedure, under an assumption of a constant hazard, the 1-year success rate of 98% yields an 
estimated 2-year anatomic success rate of 96%; combining this estimate with a similar 5% rate 
for symptom failure yields a 91% composite (anatomic and symptom) success rate. All analyses 
also assumed that statistical tests would be conducted with a Type I error rate of 0.05 with 
adjustment for multiple comparisons based on a single interim analysis. Sample size estimates 
assumed that the 2-year success rate in the mesh-augmented arm is in the range of 90% to 
93% at 24 months (note that this represents a hazard ratio in the range of 0.33 to 0.47 under the 
assumed exponential survival model), that the enrollment time for the study is 2 years, the loss-
to-follow-up on both arms is no more than 5% per year, and the total study duration from last 
participant enrolled to primary outcome analysis is 36 months with one interim analyses for 
efficacy when the last participant reaches the 24-month follow-up. Table 7 provides estimates of 
the power for the different assumptions for total sample sizes in the range of 160 to 300 
participants under the assumption that a single interim analysis will be conducted using O’Brien-
Fleming stopping rules.  
Table 7. Sample Size Calculations  
Total Sample 
Size 
Power as a Function of 2-Year Effect Size—with Base 2-Year Success 
of 80% and 36-Month Follow-Up After Last Enrollment and a 2-Year 
Enrollment Period 
Δ=0.10 
HR=0.472 
Δ=0.11 
HR=0.423 
Δ=0.12 
HR=0.374 
Δ=0.13 
HR=0.325 
160 
0.87 
0.93 
0.96 
0.99 
180 
0.89 
0.95 
0.98 
0.99 
200 
0.92 
0.96 
0.99 
>0.99 
220 
0.94 
0.98 
0.99 
>0.99 
240 
0.96 
0.98 
0.99 
>0.99 
260 
0.95 
0.99 
0.99 
>0.99 
280 
0.98 
0.99 
>0.99 
>0.99 
300 
0.98 
0.99 
>0.99 
>0.99 
Based on these calculations, a total of 180 participants will be randomized at a 1:1 ratio to the 
two treatment arms. This sample size will provide a power of 0.89 to detect an additive 
difference of 10% in the 2-year success rate (i.e. a hazard ration 0f 0.472) and a power of 0.95 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
31 
to detect additive differences of 11% or greater in the 2-year success rate (hazard ratios of 
0.423 or less).  
One of the advantages of the survival analysis approach is that the study continues to 
accumulate information on individuals enrolled early in the study as they have events beyond a 
fixed two-year or three-year time frame, particularly for a study like this one in which successes 
are more likely to occur than are failures over the first three years. As such, the survival 
approach with multiple looks will allow the analysis of the primary outcome of overall risk of 
treatment failure for the study to be completed and results published, while still collecting 
information on longer-term outcomes. 
O. 
Statistical Design 
Data analysis: 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. For the primary analysis we first generate a 
standard log-rank test to provide an overall test of difference of the two treatment regimens. We 
will then conduct model-based analyses using a generalized linear model with a complementary 
log-log link that examines failure risk as a function of treatment controlling for appropriate design 
variables site and age cohort). The model-based analyses will be used to generate an overall 
test of treatment difference using a two-sided hypothesis test with an overall Type I error rate of 
0.05, and point and interval estimates of 12-, 24- and 36-month surgical success rates on each 
treatment arm as well as well as differences in these rates on the two arms. The study has been 
designed for a single interim analysis when the last participant enrolled reaches the 24-month 
follow-up time using a Lan-DeMets alpha spending function with O’Brien-Fleming type 
boundaries. This approach will result in spending approximately 0.001 alpha at the interim 
analysis and 0.049 at the final analysis. 
Although the primary analysis will include all follow-up data from participants with follow-up time 
beyond 36 months when the study performs the primary analyses, 48- and 60-month data will 
still be limited at that time. Once all study participants have completed the 60-month follow-up 
period, a generalized linear model with a complementary log-log link that examines failure risk 
as a function of treatment controlling for appropriate design variables site and age cohort) will 
be used to conduct a secondary efficacy analysis to evaluate differences in long-term success 
between the two treatment arms. These analyses will provide an overall test of treatment 
difference using a two-sided hypothesis test with an overall Type I error rate of 0.05, and point 
and interval estimates of 48- and 30-month surgical success rates on each treatment arm as 
well as well as differences in these rates on the two arms. 
A number of secondary outcome measures that include both continuous and binary measures 
will be collected periodically across the study. To account for the correlation among the multiple 
measures on each study and to account for missing data associated with differential follow-up 
time associated with the primary design, appropriate model-based approaches (linear mixed 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
32 
models for continuous outcomes and generalized linear models for binary measures) will be 
used to compare the effects of treatment. The approach for these secondary analyses will be 
included in the statistical analysis plan. 
P. 
Ethical Concerns, Limitations, and Informed Consent 
P.1 
Ethical Concerns 
Physician bias against uterine preservation or mesh: Physicians may be reluctant to perform a 
uterine sparing, mesh supporting procedure instead of the traditional vaginal hysterectomy and 
apical suspension. Some physicians (and patients) have strong beliefs against the use of mesh, 
especially in light of the July 2011 FDA warning. We note that survey results still demonstrate 
that many AUGS members are still doing these procedures implying that this is still a relevant 
surgical problem. The mesh use in this study with the Uphold® device minimizes mesh load. All 
other repairs will be native tissue further minimizing possible mesh-related complications. The 
mesh exposure rates and complications related to mesh should be low as the mesh load is 
small, the newer Uphold® mesh is even lighter, and it is not placed adjacent to the incision. 
Furthermore, mesh erosion rates requiring OR removal would likely produce a significant 
difference in “important complications” and could lead to early study termination.   This should 
be acceptable to surgeon and patient. We believe that this study has equipoise given the 
expected similar recovery and morbidity for both procedures. If mesh apical procedures are 
comparable to mesh anterior compartment procedures then evidence for equipoise comes from 
systematic reviews66 and an RCT67 which already support improved anatomic outcomes with 
mesh in the anterior compartment. The study also has relevance given the growing trend of 
uterine sparing surgery and the widespread use of transvaginal mesh kit procedures.  
Participant bias: Women may have preferences regarding removing or conserving their uterus.  
We think evidence-based counseling on the pros and cons of both these options with emphasis 
on the importance of studying the issue will resolve this. We note that a problem somewhat 
similar to this was encountered and easily overcome in the successful randomized trials of 
supracervical vs. total hysterectomy.46, 68 Similarly, a successful RCT examined hysterectomy 
compared with endometrial ablation of dysfunctional uterine bleeding (ClinicalTrials.gov 
Identifier NCT00114088). At one site (UCSD), we have been presenting these 2 options to 
patients and have not typically encountered strong patient preferences in either direction. There 
is some concern that verbal reports from the Australia study have implied that patients equally 
choose between hysterectomy and hysteropexy, but prefer to choose rather than be 
randomized. We have heard of other countries and groups saying randomization in surgical 
trials is not possible for more than 12 years in both networks and every time this has not been 
our experience in our networks. We think that we will have fewer problems in this country and in 
this network because of our track record of effective randomization.  
Masking: All efforts will be made to mask participants and outcome evaluators, but the study 
has inherent limitations in this regard. Participants may find details of their operation on their 
surgical bill, but to minimize unmasking from a bill review we will be requesting donated 
Uphold® kits from the manufacturer. Participants may examine themselves and feel a cervix, or 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
33 
they may be told they have a cervix by another examiner. There may be health situations where 
it is necessary for them to know if they have a cervix and if so, they will be readily told by their 
study surgeon. We think it will be relatively easy to keep the study coordinator masked for 
ascertaining all outcomes other than the anatomic one. The anatomic outcome evaluator will 
need to know if the participant has a cervix or not to properly record POPQ values, but the study 
is designed so that this evaluator is a third person and has no bias towards the results. 
Perception of commercial bias: It is not unprecedented for a NIH-funded network to study a 
specific product (e.g., Botox, InterStim in the PFDN; Gynecare TVT, TVT-O and AMS Monarc in 
the UITN TOMUS study). If a non-commercial, home-made mesh bridge device was studied 
and proven inferior, proponents could argue it was the fault of a non-standardized device. For 
this reason, we favor a hysteropexy kit that lends itself to standardization. It is likely that industry 
funding will be available for this study, but industry will not participate in data collection, data 
analysis, or manuscript preparation.  
P.2 
Informed Consent 
  
Patients who are candidates for study participation will be approached for enrollment. Written 
informed consent will be obtained in accordance with Institutional Review Board guidelines. 
A common template for informed consent will be used by all centers, with modifications allowed 
to meet the necessary requirements of their respective institutional human subjects committees. 
Uterovaginal Prolapse: Eligible women will be informed that traditional treatment for uterine 
prolapse includes hysterectomy with native tissue suture support; but more recently an option is 
uterine sparing with a mesh graft suspension and we do not know which procedure is more 
successful or more durable. Advantages of hysterectomy include eliminating the possibility of 
future uterine or cervical pathology while the disadvantages are the removal of a normal organ, 
possible earlier menopause, and the risks of intra-peritoneal injury, intra-abdominal bleeding 
and vaginal shortening. The advantage of the hysteropexy procedure includes preservation of a 
normal organ, normal timing of menopause, and decreased risk of intra-peritoneal 
complications. The disadvantages include possible future uterine or cervical pathology requiring 
additional surgery. All patients will be made aware of the risks of transvaginal mesh included in 
the FDA warning (e.g. mesh erosion, pelvic pain, and dyspareunia) via the study informed 
consent statement.   
P.3 
Data and Safety Monitoring Board 
The NICHD has established a Data Safety Monitoring Board (DSMB) to oversee this study. 
Members of the DSMB are independent of the study investigators and include representatives 
with urology, urogynecology, and biostatistics expertise and a lay member. The DSMB will have 
regularly scheduled meetings, either in person or by teleconference.  The Chair may request to 
meet more frequently. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
34 
This protocol will be approved by the DSMB prior to initiation of recruitment. The DSMB will also 
monitor study progress and will have the ability to recommend that the trial be stopped for 
safety, futility, or efficacy as outlined in the paragraphs below 
At each regularly scheduled meeting of the DSMB that occurs after initiation of enrollment in the 
trial, the DSMB will review study enrollment and participant safety information and will have 
authority to recommend to the NICHD Director that the study be stopped for either safety or 
futility. While the safety guidelines described in Section M will be considered by the DSMB in 
their deliberations about study safety and futility, final stopping criteria will be established by the 
DSMB.   
The DSMB will also review efficacy data to evaluate whether to stop the study for efficacy at the 
planned formal interim analysis described in Section O. 
P.4 
Reporting of Serious Adverse Events 
Each clinical investigator is responsible for reporting serious or unexpected adverse events to 
the IRB at their institution and to the Data Coordinating Center, who will transmit the information 
to the Safety Monitor. The DCC and the Safety Monitor summarize the case and reports it to the 
NIH Program Director and to the DSMB Chair in an expedited manner. The Safety Monitor and 
Chair of the DSMB will determine whether the case should be reported to the IRBs at all the 
institutions participating in the trial. The Chair of the DSMB has the discretion to convene an 
emergency meeting of the DSMB. 
Q. 
Protocol Costs 
See separate spreadsheet.  
R. 
References 
1. 
Swift SE. The distribution of pelvic organ support in a population of female subjects seen 
for routine gynecologic health care. Am J Obstet Gynecol 2000; 183:277-85. 
2. 
Delancey JO. Fascial and muscular abnormalities in women with urethral hypermobility 
and anterior vaginal wall prolapse. Am J Obstet Gynecol 2002; 187:93-8. 
3. 
Summers A, Winkel LA, Hussain HK, DeLancey JO. The relationship between anterior 
and apical compartment support. Am J Obstet Gynecol 2006; 194:1438-43. 
4. 
Shull BL. Pelvic organ prolapse: anterior, superior, and posterior vaginal segment 
defects. Am J Obstet Gynecol 1999; 181:6-11. 
5. 
Toozs-Hobson P, Boos K, Cardozo L. Management of vaginal vault prolapse. Br J 
Obstet Gynaecol 1998; 105:13-7. 
6. 
Hsu Y, Chen L, Summers A, Ashton-Miller JA, DeLancey JO. Anterior vaginal wall length 
and degree of anterior compartment prolapse seen on dynamic MRI. Int Urogynecol J 
Pelvic Floor Dysfunct 2008; 19:137-42. 
7. 
Brown JS, Waetjen LE, Subak LL, Thom DH, Van den Eeden S, Vittinghoff E. Pelvic 
organ prolapse surgery in the United States, 1997. Am J Obstet Gynecol 2002; 186:712-
6. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
35 
8. 
Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically 
managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 1997; 89:501-
6. 
9. 
Boyles SH, Weber AM, Meyn L. Procedures for pelvic organ prolapse in the United 
States, 1979-1997. Am J Obstet Gynecol 2003; 188:108-15. 
10. 
Bump RC, Mattiasson A, Bo K, et al. The standardization of terminology of female pelvic 
organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996; 175:10-7. 
11. 
Comiter CV, Vasavada SP, Raz S. Transvaginal culdosuspension: technique and 
results. Urology 1999; 54:819-22. 
12. 
Barber MD, Visco AG, Weidner AC, Amundsen CL, Bump RC. Bilateral uterosacral 
ligament vaginal vault suspension with site-specific endopelvic fascia defect repair for 
treatment of pelvic organ prolapse. Am J Obstet Gynecol 2000; 183:1402-10; discussion 
1410-1. 
13. 
Shull BL, Bachofen C, Coates KW, Kuehl TJ. A transvaginal approach to repair of apical 
and other associated sites of pelvic organ prolapse with uterosacral ligaments. Am J 
Obstet Gynecol 2000; 183:1365-73; discussion 1373-4. 
14. 
Karram M, Goldwasser S, Kleeman S, Steele A, Vassallo B, Walsh P. High uterosacral 
vaginal vault suspension with fascial reconstruction for vaginal repair of enterocele and 
vaginal vault prolapse. Am J Obstet Gynecol 2001; 185:1339-42; discussion 1342-3. 
15. 
Amundsen CL, Flynn BJ, Webster GD. Anatomical correction of vaginal vault prolapse 
by uterosacral ligament fixation in women who also require a pubovaginal sling. J Urol 
2003; 169:1770-4. 
16. 
Silva WA, Pauls RN, Segal JL, Rooney CM, Kleeman SD, Karram MM. Uterosacral 
ligament vault suspension: five-year outcomes. Obstet Gynecol 2006; 108:255-63. 
17. 
Antovska SV, Dimitrov DG. Vaginosacral colpopexy (VSC)--a new modification of the Mc 
Call operation using vaginosacral ligaments as autologous sliding grafts in 
posthysterectomy vault prolapse. Bratisl Lek Listy 2006; 107:62-72. 
18. 
Wheeler TL, 2nd, Gerten KA, Richter HE, Duke AG, Varner RE. Outcomes of vaginal 
vault prolapse repair with a high uterosacral suspension procedure utilizing bilateral 
single sutures. Int Urogynecol J Pelvic Floor Dysfunct 2007; 18:1207-13. 
19. 
de Boer TA, Milani AL, Kluivers KB, Withagen MI, Vierhout ME. The effectiveness of 
surgical correction of uterine prolapse: cervical amputation with uterosacral ligament 
plication (modified Manchester) versus vaginal hysterectomy with high uterosacral 
ligament plication. Int Urogynecol J Pelvic Floor Dysfunct 2009; 20:1313-9. 
20. 
Doumouchtsis SK, Khunda A, Jeffery ST, Franco AV, Fynes MM. Long-term outcomes 
of modified high uterosacral ligament vault suspension (HUSLS) at vaginal 
hysterectomy. Int Urogynecol J 2011; 22:577-84. 
21. 
Richardson DA, Scotti RJ, Ostergard DR. Surgical management of uterine prolapse in 
young women. J Reprod Med 1989; 34:388-92. 
22. 
Dietz V, van der Vaart CH, van der Graaf Y, Heintz P, Schraffordt Koops SE. One-year 
follow-up after sacrospinous hysteropexy and vaginal hysterectomy for uterine descent: 
a randomized study. Int Urogynecol J; 21:209-16. 
23. 
Romanzi LJ, Tyagi R. Hysteropexy compared to hysterectomy for uterine prolapse 
surgery: does durability differ? Int Urogynecol J 2012; 23:625-31. 
24. 
FDA. Urogynecologic Surgical Mesh: Update on the Safety and Effectiveness of 
Transvaginal Placement for Pelvic Organ Prolapse. United States Food and Drug 
Administration White Paper July 2011:page 6. 
25. 
Murphy M. Clinical practice guidelines on vaginal graft use from the society of 
gynecologic surgeons. Obstet Gynecol 2008; 112:1123-30. 
26. 
Feiner B, Jelovsek JE, Maher C. Efficacy and safety of transvaginal mesh kits in the 
treatment of prolapse of the vaginal apex: a systematic review. Bjog 2009; 116:15-24. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
36 
27. 
Renganathan A, Edwards R, Duckett JR. Uterus conserving prolapse surgery--what is 
the chance of missing a malignancy? Int Urogynecol J; 21:819-21. 
28. 
Farquhar CM, Sadler L, Harvey SA, Stewart AW. The association of hysterectomy and 
menopause: a prospective cohort study. Bjog 2005; 112:956-62. 
29. 
Moorman PG, Myers ER, Schildkraut JM, Iversen ES, Wang F, Warren N. Effect of 
hysterectomy with ovarian preservation on ovarian function. Obstet Gynecol; 118:1271-
9. 
30. 
Dietz V, Schraffordt Koops SE, van der Vaart CH. Vaginal surgery for uterine descent; 
which options do we have? A review of the literature. Int Urogynecol J Pelvic Floor 
Dysfunct 2009; 20:349-56. 
31. 
Petros PE. Vault prolapse II: Restoration of dynamic vaginal supports by infracoccygeal 
sacropexy, an axial day-case vaginal procedure. Int Urogynecol J Pelvic Floor Dysfunct 
2001; 12:296-303. 
32. 
Vu MK, Letko J, Jirschele K, et al. Minimal mesh repair for apical and anterior prolapse: 
initial anatomical and subjective outcomes. Int Urogynecol J 2012. 
33. 
Carramao S, Auge AP, Pacetta AM, et al. [A randomized comparison of two vaginal 
procedures for the treatment of uterine prolapse using polypropylene mesh: hysteropexy 
versus hysterectomy]. Rev Col Bras Cir 2009; 36:65-72. 
34. 
Lunardelli JL, Auge AP, Lemos NL, et al. Polypropylene mesh vs. site-specific repair in 
the treatment of anterior vaginal wall prolapse: preliminary results of a randomized 
clinical trial. Rev Col Bras Cir 2009; 36:210-6. 
35. 
Committee Opinion no. 513: vaginal placement of synthetic mesh for pelvic organ 
prolapse. Obstet Gynecol 2011; 118:1459-64. 
36. 
Debodinance P, Fatton B, Lucot JP. [Should a hysterectomy be carried at the same time 
as surgery for a prolapse by vaginal route?]. Prog Urol 2009; 19:1060-73. 
37. 
Ehsani N ea. Risk Factors for Synthetic Mesh Extrusion Following Abdominal Sacral 
Colpopexy and Vaginal Mesh Procedures: A Fellows Pelvic Research Network Study. 
Female Pelvic Medicine and Reconstructive Surgery 2012; 18:s4. 
38. 
Barber MD, Brubaker L, Nygaard I, et al. Defining success after surgery for pelvic organ 
prolapse. Obstet Gynecol 2009; 114:600-9. 
39. 
Brubaker L, Barber MD, Nygaard I, et al. Quantification of vaginal support: are 
continuous summary scores better than POPQ stage? Am J Obstet Gynecol; 203:512 
e1-6. 
40. 
ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol 2009; 
114:1409-20. 
41.
 
http://www.acog.org/About_ACOG/Announcements/New_Cervical_Cancer_Scre
ening_Recommendations. New Cervical Cancer Screening Recommendations from the 
U.S. Preventive Services Task Force and the American Cancer Society/American 
Society for Colposcopy and Cervical Pathology/American Society for Clinical Pathology. 
42. 
McCarthy M, Jr., Jonasson O, Chang CH, et al. Assessment of patient functional status 
after surgery. J Am Coll Surg 2005; 201:171-8. 
43. 
Barber MD JN, Kenton K, Hsu Y, Greer J, Dyer K, White A, Meikle S, Ye W. Validation 
of the Surgical Pain Scales in Women undergoing Pelvic Reconstructive Surgery. In 
press 2012. 
44. 
McDermott CD, Terry CL, Woodman PJ, Hale DS. Does tension-free vaginal tape 
placement at the time of total prolift colpopexy affect distal anterior vaginal support? 
Female Pelvic Med Reconstr Surg 2010; 16:353-7. 
45. 
McDermott CD, Terry CL, Woodman PJ, Hale DS. The effect of tension-free vaginal tape 
placement on distal anterior vaginal wall support at the time of laparoscopic sacral 
colpoperineopexy. Arch Gynecol Obstet 2011; 283:1303-7. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
37 
46. 
Thakar R, Ayers S, Clarkson P, Stanton S, Manyonda I. Outcomes after total versus 
subtotal abdominal hysterectomy. N Engl J Med 2002; 347:1318-25. 
47. 
Barber MD, Neubauer NL, Klein-Olarte V. Can we screen for pelvic organ prolapse 
without a physical examination in epidemiologic studies? Am J Obstet Gynecol 2006; 
195:942-8. 
48. 
Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. 
Am J Obstet Gynecol 2003; 189:98-101. 
49. 
Barber MD, Kuchibhatla MN, Pieper CF, Bump RC. Psychometric evaluation of 2 
comprehensive condition-specific quality of life instruments for women with pelvic floor 
disorders. Am J Obstet Gynecol 2001; 185:1388-95. 
50. 
Rogers RG, Coates KW, Kammerer-Doak D, Khalsa S, Qualls C. A short form of the 
Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Int 
Urogynecol J Pelvic Floor Dysfunct 2003; 14:164-8; discussion 168. 
51. 
Ware JE, Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. 
Conceptual framework and item selection. Med Care 1992; 30:473-83. 
52. 
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new 
proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 
2004; 240:205-13. 
53. 
Brazier JE, Roberts J. The estimation of a preference-based measure of health from the 
SF-12. Med Care 2004; 42:851-9. 
54. 
Hollingworth W, Campbell JD, Kowalski J, et al. Exploring the impact of changes in 
neurogenic urinary incontinence frequency and condition-specific quality of life on 
preference-based outcomes. Qual Life Res 2010; 19:323-31. 
55. 
McCulloch CE SS. Generalized, linear, and mixed models. New York: John Wiley, 2001. 
56. 
Efron B TR. An introduction to the bootstrap. New York: Chapman and Hall, 1993. 
57. 
Subak LL, Brubaker L, Chai TC, et al. High costs of urinary incontinence among women 
electing surgery to treat stress incontinence. Obstet Gynecol 2008; 111:899-907. 
58. 
Cash T. The psychology of physical appearance: Aesthetics, attributes, and images. In: 
TF Cash and t PRuzinsky (Eds), ed. New York: Guilford Press. 
59. 
Hopwood P, Fletcher I, Lee A, Al Ghazal S. A body image scale for use with cancer 
patients. Eur J Cancer 2001; 37:189-97. 
60. 
Jelovsek JE, Barber MD. Women seeking treatment for advanced pelvic organ prolapse 
have decreased body image and quality of life. Am J Obstet Gynecol 2006; 194:1455-
61. 
61. 
Lowenstein L, Gamble T, Sanses TV, et al. Changes in sexual function after treatment 
for prolapse are related to the improvement in body image perception. J Sex Med 2010; 
7:1023-8. 
62. 
Lowenstein L, Gamble T, Sanses TV, et al. Sexual function is related to body image 
perception in women with pelvic organ prolapse. J Sex Med 2009; 6:2286-91. 
63. 
Lowder JL, Ghetti C, Nikolajski C, Oliphant SS, Zyczynski HM. Body image perceptions 
in women with pelvic organ prolapse: a qualitative study. Am J Obstet Gynecol 2011; 
204:441 e1-5. 
64. 
Lowder JL, Ghetti C, Moalli P, Zyczynski H, Cash TF. Body image in women before and 
after reconstructive surgery for pelvic organ prolapse. Int Urogynecol J 2010; 21:919-25. 
65. 
Patel M, Mellen C, O'Sullivan DM, LaSala CA. Impact of pessary use on prolapse 
symptoms, quality of life, and body image. Am J Obstet Gynecol 2010; 202:499 e1-4. 
66. 
Sung VW, Rogers RG, Schaffer JI, et al. Graft use in transvaginal pelvic organ prolapse 
repair: a systematic review. Obstet Gynecol 2008; 112:1131-42. 
67. 
Nguyen JN, Burchette RJ. Outcome after anterior vaginal prolapse repair: a randomized 
controlled trial. Obstet Gynecol 2008; 111:891-8. 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
38 
68. 
Learman LA, Summitt RL, Jr., Varner RE, et al. A randomized comparison of total or 
supracervical hysterectomy: surgical complications and clinical outcomes. Obstet 
Gynecol 2003; 102:453-62. 
 
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
39 
S.  Appendices 
Appendix A. Figures  
Figures demonstrating the 2 operations proposed in the SUPeR protocol (illustrations by 
Jasmine Tan-Kim, MD). 
Figure A. Hysterectomy with uterosacral ligament 
suspension 
Figure B. Uterine sparing apical mesh suspension 
(hysteropexy)  
 
  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
40 
Appendix B. Planned Study Timeline 
Milestone Date 
Description of Milestone 
December 2012 
Final Protocol Version 1.0 available for submission to FDA 
and site IRBs 
March 2013 
Randomize first participant 
March 2015 
Enrollment Complete 
March 2017 
Conduct Interim Analysis when last participant reaches 2-
year follow-up 
March 2018 
Last participant reaches 3-year follow-up 
August 2018 
Final study report submitted to BSC 
October 2018 
Final study report submitted to FDA 
 
 
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
41 
T. 
AMENDMENT – REVISED: CLARIFICATION OF LENGTH OF SUBJECT 
PARTICIPATION  
• 
We removed the last sentence of the original version of this amendment. The 
inclusion of this sentence was an accidental oversight of a decision from when 
the protocol committee was considering an extension to the SUPeR study (i.e. e-
SUPeR). The intent of this decision was to help facilitate a clear separation of the 
studies and assist with enrollment. 
• 
The last sentence of the original version of this amendment has been replaced 
with an explicit statement regarding when participants should be unmasked. 
Background 
The primary aim of SUPeR was to determine whether treatment success in women with 
symptomatic uterovaginal prolapse undergoing transvaginal mesh augmented hysteropexy 
differs in women undergoing vaginal hysterectomy and native tissue cuff suspension at time 
points through 3 years. The study was designed with a survival analysis approach with 36 
month follow-up after last enrollment with an expected 2 year enrollment period. SUPeR 
randomization began in April 2013, enrollment ended in October 2014, and the last surgery 
(randomization) was performed in January 2015. Because there is a 6 week window for the final 
visit, we will have 3 year data on all continuing participants by March 2018. By April 2018, 
subjects in SUPeR will have been followed every 6 months for 3 to 5 years. The primary 
outcome should be available by April 2018.   
As the protocol states, one of the advantages of the survival analysis approach is that the study 
continues to accumulate information on individuals enrolled early in the study as they have 
events beyond the three-year time frame. The protocol states, “As such, the survival approach 
with multiple looks will allow the analysis of the primary outcome of overall risk of treatment 
failure for the study to be completed and results published, while still collecting information on 
longer-term outcomes.” This clearly implies the intention of continuing to collect data for all 
subjects every 6 months for 5 years. Indeed, the schedule of measures, the study budget and 
the informed consent to patients emphasized every 6 month visits up to 5 years (60 months). All 
subjects were consented to participate in SUPeR and undergo visits every 6 months for up to 5 
years (60 months). The 30, 42, and 54 month visits are abbreviated visits that collect data for 
the primary and major secondary outcomes (POPQ, mesh exam, PFDI-Q3, and AE survey).  
Some investigators had interpreted that the study ends when the last patient reaches the 3 year 
follow-up. There is ambiguity in the protocol and in the compensation section of the consent 
form that suggests that not everyone might complete 60 months of visits.  
Purpose 
The purpose of this amendment is to clarify the length of subject participation.  
• 
We clarify that all subjects should be followed every 6 months for 60 months (5 
years).  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
42 
In support of this clarification we note:  
1. The schedule of measures, the study budget and the informed consent to patients 
emphasized every 6 month visits up to 5 years (60 months). Patients were consented 
and agreed to every 6 month visits for up to 60 months (5 years) 
2. We believe that this amendment does not require reconsenting subjects at most sites 
because subjects were consented to every 6 month visits for up to 60 months. However, 
this decision is made by each local IRB.   
All participants should be unmasked by a study coordinator at the completion of their 60-month 
study visit.  
 
 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
43 
U. 
AMENDMENT: EXTENSION OF THE STUDY OF UTERINE PROLAPSE 
PROCEDURES-RANDOMIZED TRIAL (SUPeR) STUDY FOR LONG-TERM 
FOLLOW-UP TO 10 YEARS (E-SUPeR) 
Background 
The primary aim of SUPeR was to determine whether treatment success in women with 
symptomatic uterovaginal prolapse undergoing transvaginal mesh augmented hysteropexy 
differs in women undergoing vaginal hysterectomy and native tissue cuff suspension at time 
points through 3 years. The study was designed with a survival analysis approach with 36 
month follow-up after last enrollment with an expected 2 year enrollment period. SUPeR 
randomization began in April 2013, enrollment ended in October 2014, and the last surgery 
(randomization) was performed in January 2015. All subjects reached 3 year follow-up in March 
2018. Retention in this time period was excellent; three year primary outcome data was 
available for 96% of the participants. Some participants have reached the 5 year follow-up time 
point and have been unmasked. 
What has become apparent with this excellent follow-up is that the SUPeR cohort represents a 
unique opportunity to understand the longer term efficacy and safety outcomes of a native 
tissue repair and a mesh hysteropexy. There are no studies in the literature with such 
outstanding long-term follow-up over an extended period of time. The current 96% retention rate 
underscores how readily participants accept the evaluations  that have been performed in this 
study.  
Proposed Extension of Study 
This amendment proposes to continue to follow the subjects in this study who have not 
undergone reoperation for prolapse until reoperation for prolapse is reported, 10 years of follow-
up  is completed, or until participant retention in this study falls below 60%. To decrease subject 
burden, the frequency of study visits will be reduced from every 6 months to annually from the 
date of surgery. A reduction of select secondary patient reported outcome measures that are 
unlikely to provide interesting data during this 5-10 year time period is proposed.   
The annual follow-up visits for year 6 could begin as early as April 2019 when our first subject 
reaches the 6 year mark. The table below represents the abbreviated outcome measures that 
will be collected at each annual visit.   
Measure 
6 years 
7 years 8 years 9 years 10 years 
POPQ  
X 
X 
X 
X 
X 
AE review  
X 
X 
X 
X 
X 
Exam for mesh exposure  
X 
X 
X 
X 
X 
PFDI-20 (includes POPDI-6, CRADI-8, 
UDI-6) 
X 
X 
X 
X 
X 

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
44 
Measure 
6 years 
7 years 8 years 9 years 10 years 
PFIQ 
X 
X 
X 
X 
X 
PGI-I  
X 
X 
X 
X 
X 
ISI 
X 
X 
X 
X 
X 
PISQ-IR 
X 
X 
X 
X 
X 
The measures that are unlikely to add significant value to the outcome measures and have 
been removed from these annual assessments are: 
• 
Functional Activity Scale 
• 
Surgical Pain Scale 
• 
BIS 
• 
SF-12 
Limited (Virtual) Participation Option 
The following subjects can be offered the opportunity to consent to limited study participation: 
participants who discontinued, withdrew consent, were withdrawn by investigator, or were lost to 
follow-up during the initial 5-year SUPeR study, and subjects who initially declined to enroll in E-
SUPeR. All of the subjects described will be approached so as not to introduce bias, provided 
that the local site IRB determines it is appropriate to approach these participants for consent to 
this alternative less burdensome option. The limited study participation option excludes the in-
person visit and physical exam and includes study assessments that can be completed remotely 
(i.e., via phone, mail, or internet.)      
The table below represents the outcome measures that will be collected at each annual visit 
under the limited participation option. 
Measure 
6 years 
7 years 8 years 9 years 10 years 
AE review  
X 
X 
X 
X 
X 
PFDI-20 (includes POPDI-6, CRADI-8, 
UDI-6)  
X 
X 
X 
X 
X 
PFIQ  
X 
X 
X 
X 
X 
PGI-I  
X 
X 
X 
X 
X 
ISI  
X 
X 
X 
X 
X 
PISQ-IR  
X 
X 
X 
X 
X 
 
Adverse Event Collection and Reporting  

Pelvic Floor Disorders Network 
SUPeR, Protocol 24P01 
 
Confidential Please Do Not Copy 
Version 5.0 October 9, 2020 
45 
The E-SUPeR study is an observational extension of the original SUPeR protocol and does not 
involve a treatment intervention. A primary goal of E-SUPeR is to ascertain the long-term failure 
rates associated with vaginal hysterectomy plus uterosacral ligament suspension and mesh 
hysteropexy. Therefore, negative outcomes that may be related to these procedures, as 
evidenced by treatments or re-operation for prolapse or incontinence, suture or mesh erosions, 
and periurethral implants for stress incontinence (such as collagen) will be collected by the 
study coordinator at the time of the annual visit and reported to the DSMB in summary format. 
Similarly, any additional pelvic (urologic, colorectal, and gynecological) surgery will be collected 
annually and reported to the DSMB in summary format.   
Outcomes that are not likely related to native tissue repair or mesh hysteropexy (i.e., non-
urologic/non-colorectal/non-gynecologic diagnoses, procedures and hospitalizations) will not be 
collected. Outcomes classified as serious adverse events (SAEs), defined as all deaths and 
SAEs that are considered related to the index surgery of SUPeR or the pelvis, will be reported 
to the Medical Safety Monitor, DSMB, site IRB (per local IRB requirements), and NICHDIRB in 
an expedited manner. By definition, as E-SUPeR starts five years after the randomization for the 
index surgery of SUPeR, fatalities will most likely not be related to native tissue repair or mesh 
hysteropexy, but all fatalities regardless of relationship to the study surgeries will be collected 
for E-SUPeR. 
Sample Size Estimate 
The available cohort includes a total of N = 156 subjects after excluding those initially ineligible 
for the SUPeR study, deaths, and those who have had a second surgery secondary to index 
surgery failure during the 5year SUPeR study. Any participants who undergo reoperation for 
prolapse between completing the 5-year SUPeR study and being assessed for E-SUPeR will be 
considered eligible for the extension. Limited data regarding the second surgery will be collected 
and then the subject’s participation will end immediately thereafter.  It is anticipated that the 
number of participants in follow up will be reduced by approximately 5% per year due to either 
withdrawal or reoperation for prolapse. 
Feasibility and Statistical Analysis 
If overall participant retention drops below 60%, the study will be terminated so that 
unnecessary burden without appreciable benefits is not placed on the participants or the study 
investigators. 
Once the study is completed, differences between the treatment groups in long-term surgical 
success and other outcomes will be evaluated using statistical methods consistent with the 
analyses performed at 3 and 5 years.