Randomized Trial of Retropubic Versus Single-incision Mid-Urethral Sling (Altis ) for Concomitant Management of Stress Urinary Incontinence During Native Tissue Vaginal Repair
Phase: NA
Conditions: Stress Urinary Incontinence, Pelvic Floor Disorders
Sponsor: Wake Forest University Health Sciences

Protocol Version Number: 20 
Date: 1/10/2020 
1 
 Randomized trial of Retropubic versus Single-incision Mid-Urethral Sling 
(Altis™) for Concomitant Management of Stress urinary incontinence 
during Native Tissue Vaginal Repair 
 
Principal Investigator: 
Catherine Matthews, MD 
 
 
 
 
Wake Forest Baptist Health, Winston Salem, NC 
 
Co-Investigators: 
 
Candace Parker-Autry, MD 
 
 
 
 
Wake Forest Baptist Health, Winston Salem, NC 
 
 
 
 
 
 
Robert Gutman, MD (Site PI) 
 
 
 
 
Cheryl Iglesia, MD 
 
 
 
 
Amy Park, MD 
 
 
 
 
Andrew Sokol, MD 
 
 
 
 
MedStar Washington Hospital Center/Georgetown   
 
 
 
 
University, Washington, DC 
 
 
 
 
 
Kimberly Kenton, MD, MS (Site PI) 
 
 
 
 
Margaret Mueller, MD 
 
 
 
 
Sarah Collins, MD 
 
 
 
 
Christina Lewicky-Gaupp, MD 
 
 
 
 
Northwestern, Chicago, IL 
 
 
 
 
 
Charles Rardin, MD (Site PI) 
 
 
Women and Infants Hospital of Rhode Island  
Providence, RI 
 
 
 
 
 
Cecile Unger, MD (Site PI) 
 
 
 
 
Marie Fidela Paraiso, MD 
 
 
 
 
Mark Walters, MD 
 
 
 
 
Cleveland Clinic, Cleveland OH 
 
 
 
 
 
Erinn Myers, MD (Site PI) 
 
 
 
 
Kevin Stepp, MD 
 
 
 
 
Bernard Taylor, MD 
 
 
 
 
Megan Tarr, MD 
 
 
 
 
Michael J. Kennelly, MD 
 
 
 
 
Atrium Health, Charlotte, NC 
 
 
Stephen Jeffery, MD (Site PI)           
Kendall Brouard, MD 
Lamees Ras, MD 
Erika Drewes, MD 
Dakalo Muavha, MD 
University of Cape Town, South Africa 
 
 
 
 
 
J.P. Roovers, MD, PhD (Statistical support) 
 
 
 
 
The Netherlands 
 
 

Protocol Version Number: 20 
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INDEX 
 
 
 
 
 
 
 
 
 
 
 
     Pages 
1. Protocol signature confirmation 
 
 
 
 
3 
2. Background and Significance  
 
 
 
 
4-7 
3. Study Objectives  
 
 
 
 
 
 
8 
4. Subject selection: Inclusion/exclusion  
 
 
 
9 
5. Study population, selection and recruitment  
 
 
10 
6. Pre-Intervention Assessments  
 
 
 
 
11,12 
7. Randomization and masking 
 
 
 
 
 
12 
8. Study Intervention 
 
 
 
 
 
 
12,13 
9. Post-intervention Assessments  
 
 
 
 
13,14 
10. Power calculation 
 
 
 
 
 
 
14,15 
11. Calendar of Events 
 
 
 
 
 
 
15 
12.  Data Collection & Management 
 
 
 
 
15,16 
13.  Study Monitoring and Documentation 
 
 
 
16 
12. Reporting Adverse Events 
 
 
 
 
 
17,18  
 
13. Subject Protections 
 
 
 
 
 
 
21 
14. Authorship 
 
 
 
 
 
 
 
21,22 
14. References 
 
 
 
 
 
 
 
23,24 
 
 
 

Protocol Version Number: 20 
Date: 1/10/2020 
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INVESTIGATOR’S SIGNATURE PAGE—Version 20: 1/10/2020  
 
 
 
Randomized trial of Retropubic versus Single-incision Mid-Urethral Sling 
(Altis™) for Concomitant Management of Stress urinary incontinence 
during Native Tissue Vaginal Repair 
 
The signature below constitutes the approval of this protocol and the attachments, 
and provides the necessary assurances that this trial will be conducted according 
to all stipulations of the protocol, including all statements regarding confidentiality, 
and according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
 
 
Investigator:  ____________________________________ 
                         Printed Name and Title 
 
 
Signed:  
Date:  
 
Name and Title 
 
 
 
 
 
[PAGE TO BE PRINTED AND SIGNED WITH EACH FINAL PROTOCOL 
VERSION] 
 
 
 
 
 
 
Name and Address of Institution:  
__________________________________________ 
 
 
 
 
                              
__________________________________________ 
 
 
 
 
                              
__________________________________________ 
 
 
                              
__________________________________________ 
 

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BACKGROUND AND SIGNIFICANCE 
 
Surgical decision making regarding concomitant management of pelvic organ 
prolapse (POP) and symptomatic or “occult” stress urinary incontinence (SUI) is 
complex and controversial.1 One in five women will undergo prolapse surgery in 
their lifetime, and there is a strong correlation between prolapse and urinary 
incontinence. 2,3  
Pelvic floor surgeons aspire to improve relevant quality of life outcomes for women 
with pelvic floor disorders while minimizing complications and unnecessary 
procedures. Consider the patient who has POP and SUI who undergoes an 
extensive vaginal repair and synthetic sling and then suffers from prolonged 
urinary retention post-operatively without a clear answer as to the etiology. 
Similarly, we have also experienced disappointment and frustration when a patient 
returns following POP repair with new symptoms of SUI that she ranks as a greater 
disruption to her quality of life than her original vaginal bulge. Another potential 
troublesome scenario is a significant surgical complication such as post-operative 
pain or voiding dysfunction that occurs during the placement of a “prophylactic” 
sling for “occult” SUI. 
Efficacy and risk always compete for equilibrium. Level I evidence has 
demonstrated a positive efficacy benefit of a concomitant synthetic mid-urethral 
sling in women with 4, and without 5, pre-operative symptoms of SUI who are 
undergoing POP repair. Surgical correction of prolapse, with elevation of the 
vaginal apex and straightening of the angle between the bladder base and the 
urethra, has the potential to increase existing, or unmask “occult” SUI symptoms.6  
Concomitant sling placement has been shown to reduce the risk of de novo or 
persistent SUI from 50% to 23%.5 The combination of surgical treatment of POP 
and SUI at the same time, however, increases the risk of incomplete bladder 
emptying.5 There is a delicate balance between placing a sling that is tight enough 
to prevent SUI but loose enough to allow normal voiding function. This is the 
primary justification of surgeons who employ a staged approach and elect only to 
treat those who develop bothersome SUI postoperatively.  
The type of synthetic sling that is utilized during the combined treatment approach, 
however, can influence this balance between efficacy and risk. Slings can be 
placed via the retropubic (RP, see Figure 1), trans-obturator (TO, see Figure 2) or 
single-incision (SIS, see Figure 3) approaches. While RP slings are considered to 
be the “gold-standard” referent for other slings with long-term outcomes data 7, 
they are associated with the highest risks of intra- and post-operative 
complications including bladder injury, bleeding, and post-operative voiding 
dysfunction.8,9,10 Trans-obturator slings were introduced to avoid the potential 
complications associated with RP placement. Clinical trials have demonstrated 
that TO slings are associated with equivalent subjective cure rates to RP slings, 
with less voiding dysfunction and fewer bladder perforations.8,9,11-13  However, TO 
slings have lower objective cure rates and have greater risk of postoperative 

Protocol Version Number: 20 
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5 
neurologic symptoms in the obturator region.8,9,12  
 
Single-incision slings (SIS) are the latest iteration in sling development that build 
upon the benefits of TO slings but avoid passage through the muscles of the inner 
thigh. The first prototype SIS was secured behind the symphysis with a metal 
anchor system and was proven inferior to retropubic slings in treatment efficacy.4,14 
Later designs that employ an anchor system in the obturator membrane 
demonstrated efficacious one to five-year outcomes with significantly lower risks 
of voiding dysfunction and thigh pain than TOT slings.15-18 A reduction in post-
operative pain appears highly important to women. Schellart et al evaluated patient 
preferences for SUI efficacy versus pain and determined that women are willing to 
trade 4% less efficacy for a significant reduction of 2 days less pain and a 7% 
reduction in efficacy for 2 weeks’ worth of less pain.19 There is one published trial 
of concomitant SIS placement at the time of robotic-assisted sacral colpopexy that 
reported a 0% voiding dysfunction rate and 87% cure at 1 year.20 
The Altis ™ SIS sling (Coloplast, Minneapolis, MD) consists of a knitted, 
monofilament, macroporous polypropylene mesh that measures 7.75 cm long. The 
mesh is characterized by low elasticity (7.5 %), which allows the maintenance of 
integrity under tension with no banding or cording under the urethra. The system 
has a fixed anchor on one side and an adjustable anchor on the opposite side. 
This design is intended to facilitate surgical ease of tensioning the sling: the 
prolene tensioning suture can be gradually tightened or loosened to achieve the 
desired effect on the continence mechanism. Clinical trials regarding this particular 
sling are very limited. Two prospective, non-comparative trials reported cure rates 
of 84% at 12 months21 and 81% at 24 months22, respectively. There were no cases 
of post-operative voiding dysfunction or groin pain reported in these two trials. At 
two years, a 3.5% rate of mesh exposure was noted.22  
As the combination of POP and sling surgery increases the risk of voiding 
dysfunction, and rates of incomplete bladder emptying appear significantly lower 
for SIS than RP slings, we hypothesize that the use of the Altis ™ SIS will be non-
inferior to RP slings in efficacy and superior in irritative voiding symptoms/voiding 
dysfunction at one year after combined surgery. The primary objective of this 
multicenter, prospective, single-blind randomized controlled trial, therefore, is to 
test this hypothesis for women with objective stress incontinence (symptomatic or 
occult) who are undergoing native tissue vaginal repair, including colpocleisis. The 
chosen composite primary outcome of abnormal lower urinary tract function is 
designed to assess the balanced effects on efficacy versus voiding dysfunction. 
Secondary outcomes will assess relative differences in pain and complications. 
 
 
 
 

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Figure 1: Retropubic sling  
 
   
 
  
Figure 2: Transobturator sling 
 
Figure 3: Single-incision sling- blue lines represent where the SIS mesh 
terminates in the obturator membrane 
 
 
 
 
 
 

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Figure 4: Altis single-incision sling and delivery system 
 
 
 

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PRIMARY STUDY OBJECTIVES 
 
 
Hypothesis 1: Single-incision slings (Altis ™) are non-inferior to Retropubic 
mid-urethral slings when placed concomitantly at the time of native tissue 
vaginal repair, including colpocleisis. 
 
Specific Aim 1: 
To conduct a multi-center, prospective, randomized, single-blind trial of retropubic 
(RP) versus single-incision sling (SIS) in women with ≥ Stage II pelvic organ 
prolapse and objectively confirmed stress urinary incontinence who are 
undergoing native tissue vaginal repair.  
The primary outcome will be abnormal lower urinary tract function, a 
composite outcome defined as the presence of any the following at 1 year post-
surgery: subjective stress incontinence symptoms or retreatment for persistent / 
de novo stress urinary incontinence or retreatment for urinary retention. This study 
is a non-inferiority study design. 
 
Hypothesis 2: SIS is associated with fewer intra-and post-operative 
complications up to 1 year following surgery due to fewer sling related 
complications including urinary tract injury; bleeding; de novo or worsening 
urge incontinence symptoms; urinary tract infection, mesh exposure, need 
for prolonged catheter drainage and reoperations than RP slings. 
Specific Aim 2: 
To compare intra- and post-operative sling related complications, de novo or 
worsening urge incontinence symptoms and need for prolonged bladder drainage 
up to 1 year post-operatively in women randomized to RP versus SIS sling at the 
time of native tissue vaginal repair. 
 
 
 
 

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SUBJECT SELECTION 
 
Inclusion Criteria 
 
 
1. At least 21 years of age 
2. Women being considered for a native tissue vaginal repair in any vaginal 
compartment or colpocleisis 
3. POP ≥ stage II of any vaginal compartment, according to the pelvic organ 
prolapse quantification (POP-Q) system [31] 
4. Vaginal bulge symptoms as indicated by an affirmative response to question 
3 of the PFDI-SF20 with some degree of bother (answer must be somewhat, 
moderately, or quite a bit): Do you usually have a bulge or something falling 
out that you can see or feel in the vaginal area? 
 
5. Positive standardized cough stress test on clinical examination, or on 
urodynamic testing 
6. Understanding and acceptance of the need to return for all scheduled 
follow-up visits and willing to complete study questionnaires 
7. Able to give informed consent 
 
Exclusion Criteria 
1. Prior surgery for stress urinary incontinence including mid-urethral sling; 
Burch/MMK; fascial pubovaginal sling (autologous, xenograft or allograft; 
urethral bulking injection 
2. Status post reconstructive pelvic surgery with transvaginal mesh kits or 
sacrocolpopexy with synthetic mesh for prolapse 
3. Any serious disease, or chronic condition, that could interfere with the study 
compliance 
4. Unwilling to have a synthetic sling 
5. Inability to give informed consent 
6. Pregnancy or planning pregnancy in the first postoperative year  
7. Untreated urinary tract infection (may be included after resolution) 
8. Poorly-controlled diabetes mellitus (HgbA1c > 9 within 3 months of surgery 
date) 
9. Prior pelvic radiation 
10. Incarcerated    
11. Neurogenic bladder/ pre-operative self-catheterization 
12. Elevated post-void residual (>150 ml) that does not resolve with prolapse 
reduction testing (pessary, prolapse reduced uroflow or micturition study) 
13. Prior augmented (synthetic mesh, autologous graft, xenograft, allograft) 
prolapse repair  
14. Planned concomitant bowel related surgery including sphincteroplasty and 
perineal 
rectal 
prolapse 
surgery, 
rectovaginal 
fistula 
repair, 
hemorrhoidectomy. 

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STUDY POPULATION, RECRUITMENT AND SCREENING 
 
Study population participants will consist of women having native tissue vaginal 
repair in any vaginal compartment. Participants must have vaginal bulge 
symptoms defined by positive responses to a validated instrument, the Pelvic Floor 
Distress Inventory23 and Stage II or greater POP in any vaginal compartment as 
determined by the Pelvic Organ Prolapse Quantification (POPQ) system24, a 
validated tool designed to assess the degree of vaginal prolapse. Participants must 
have objective evidence of stress incontinence on physical examination, with or 
without prolapse reduction, or on urodynamic testing. Women will be grouped 
according to whether they have SYMPTOMATIC or OCCULT SUI for 
randomization purposes. 
 
Study subjects will be recruited from patients who present to the urogynecology 
clinical sites at Wake Forest Baptist Health, the Women’s Health Institute at the 
Cleveland Clinic, Northwestern, MedStar Washington Hospital Center, Women’s 
and Infants’ Hospital of Rhode Island, Atrium Health, and Groote Schuur Hospital 
at the University of Cape Town, and the private practice clinic of Dr. Jeffery. Wake 
Forest Baptist Health will serve as the central Data Coordinating Center. 
Institutional review board (IRB) approval will be obtained at each participating site. 
 
Potential subjects will be identified by members of the sections of Urogynecology 
and Reconstructive Pelvic Surgery and Benign Gynecology at the respective 
institutions. Eligible patients who agree to participate will be provided written 
informed consent administered by the collaborators listed on each Institutional IRB 
document. 
 
 

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PRE-INTERVENTION ASSESSMENTS: 
 
All women presenting to the participating clinical centers with signs and symptoms 
of prolapse and objective stress incontinence (symptomatic or occult) will be 
screened for their eligibility. If eligible and consenting, the following baseline data 
will be collected on paper forms that will then be transcribed into a secure RedCap 
database:  
 
1. Demographic data including age, race, BMI, insurance     
     
    
    
status 
 
2. Health-related quality of life (SF-12), and measurement of   
   
     
 
Charlson Comorbidity Index 
3. Smoking status (Yes or No) 
4. POP-Q data 
5. Presence of vaginal atrophy (Yes or No) 
6. Menopausal status,including current exposure to topical vaginal               
    
estrogen, parity, and urogynecologic surgeries  
7. Current exposure to anticholinergic medication (Yes or No) 
8. Objective assessment of stress incontinence: Clinical or urodynamic 
assessment is permitted.  
a. Clinical cough stress test: Participants that have no prior objective SUI 
will be instructed to present with a full bladder  . If empty, the bladder can 
be retrograde filled with 300 ml. In the lithotomy position, subjects will be 
asked to cough and strain (Valsalva) while the urethral meatus is 
observed and the POP is reduced. If no leakage is demonstrated, the 
reduction cough stress test will be repeated in the standing position. 
Women will be categorized as having symptomatic vs occult SUI for 
sub-analysis and block randomization. 
b. Urodynamic testing: Participants may undergo standard urodynamic 
testing with prolapse reduction. A cough stress test at bladder capacity will 
be performed. If no leakage is demonstrated at capacity with the catheters 
in place, the catheters will be removed and the cough stress test repeated. 
Valsalva leak point pressures will be recorded. 
9. Assessment of post-void residual volume (collected via bladder scan or CIC) 
10. A series of instruments will be used to measure symptom bother: the Pelvic 
Floor Distress Inventory short form-20,23  Pelvic Organ Prolapse/Urinary 
Incontinence Sexual Functioning Questionnaire Short Form (PISQ-IR)25  and 
PFIQ-7. 
 
NOTE:  Standard of care assessments (POP-Q, UDS, PVRs) are valid to use for 
the study if they were performed within 6 months of the subject signing consent.  
Also, if any standard of care questionnaires (matching the study questionnaires) 
were administered within 6 months before signing consent, they may also be used 

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in the place of baseline questionnaires and not repeated.  Dates of assessments 
just need to be clear if they were not performed the same day as baseline.  Also, 
make sure all assessments required for the study have been performed per 
baseline visit requirements.   
RANDOMIZATION AND MASKING: 
A computer-generated random allocation using a randomly permutated block 
design (10 subjects per block) will be stratified by clinical site and presence of 
symptomatic versus occult SUI. Randomization will be assigned in the operating 
room to minimize surgeon and participant bias. While it is impossible for surgeons 
to be masked to the randomization, participants will be masked during the one-
year follow-up period. Dictated operative notes will list the type of sling under 
procedures as “per study protocol” and then describe the type of sling used within 
the body of the operative note. Precautions will be taken to minimize unmasking 
the study groups: Since RP slings require two suprapubic stab incisions, identical 
sham incision will also be performed in the SIS group. Surgical wound dressings 
will be identical for all participants. Finally, all participants, regardless of 
randomization, will have postoperative indwelling urethral catheters until voiding 
trials are performed.  
 
STUDY INTERVENTION: 
 
The primary intervention is concomitant placement of any full-length macroporous, 
monofilament polypropylene bottom-up Retropubic Sling (manufactured by Boston 
Scientific; Ethicon; Caldera; or Neomed) VERSUS Altis™ single-incision sling 
(Coloplast, Minneapolis, MN) during completion of native tissue vaginal repair, 
including colpocleisis. If an anterior or apical procedure is planned, the sling must 
be tensioned following completion of these steps. Prolapse procedures will be 
recorded but not controlled by study protocol. Participating surgeons are all 
extensively experienced in RP sling passage and are required to have performed 
at least 5 SIS procedures prior to enrolling participants in this trial. In order to 
minimize the risk of altering the urethrovesical angle and the likelihood of 
postoperative stress urinary incontinence, any anterior repair will be conducted 
using an incision proximal to the bladder neck level and separate from sling 
incisions. Allowable techniques for prolapse repair include anterior and posterior 
colporrhaphy (plication of fibromuscular vaginal tissue), vaginal paravaginal repair, 
sacrospinous ligament suspension (either of uterus or vaginal apex), uterosacral 
ligament suspension (either of uterus or vaginal apex, through vaginal or 
laparoscopic approach) levator plication or colpocleisis. Any use of allograft, 
xenograft, or synthetic graft material for POP repair will not be permitted.  
 
 
 
 
 
 

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Standardized technique of RP sling placement 
 
Retropubic procedures will all be performed using the vaginal or “bottom-up” 
approach as described by the manufacturers (Ethicon; Boston Scientific; Caldera; 
Neomed).  Subjects will be placed in Trendelenburg position, the legs lowered to 
lithotomy position, and the bladder completely drained. A 1.5 cm incision will be 
made at the mid-urethra through a separate vaginal incision with lateral dissection 
with Metzembaum scissors. After placement of both trocars, cystoscopy with a 70-
degree scope will be performed to assess for bladder and urethral injury. Surgeons 
will set the tension of the TVT slings so that a spacer can be placed between the 
sling and the urethra. Sling tensioning will be performed after anterior and apical 
prolapse is corrected. Dermabond or steri strips will be applied to the suprapubic 
exit incisions. 
 
Standardized technique of SIS placement 
 
All surgeons will watch a standardized video regarding SIS sling placement prior 
to study launch. A 1.5 cm incision will be made at the level of the mid-urethra, The 
sling/needle assembly is advanced behind the ischiopubic rami in a transobturator 
trajectory toward the obturator space bilaterally.The needle is then removed by 
simply sliding the fixating tip back out. The other side is then completed in an 
identical fashion. The sling will be tensioned so that it will lie in direct apposition to 
the urethra but will still permit passage of an instrument between the mesh and the 
urethra. The adjustment thread is then cut short and the vaginal incision is closed 
with an absorbable suture. 
 
Following SIS placement, 2 small superficial skin incisions will be made in the 
same location as the exit sites of a RP sling. Dermabond or steri strips will be 
applied. 
 
Any intra-operative adverse events will be recorded on data collection forms. 
 
Post-operative care and procedures for voiding trials will not be standardized. Day 
of discharge and method of voiding (spontaneous, self-catheterization, suprapubic 
catheter, or indwelling foley) will be recorded.  
 
POST-INTERVENTION ASSESSMENTS: 
 
The primary study endpoints will be assessed at 6 weeks and 12 months after the 
index surgery via a clinic visit and health-related quality of life interview/completion 
of questionnaires. Individual site study coordinators will collect follow-up 
healthcare utilization data and update the medical history at 6 and 12 months. 
Study coordinators will complete a telephone interview at 6 months to assess for 
any Adverse Events.  
 
 

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Clinical outcomes  
 
This trial has a composite primary dichotomous outcome of abnormal lower 
urinary tract function at 12 months post-operatively (YES or NO) that is defined 
as ANY of the following: 
 
1. Subjectively bothersome stress incontinence symptoms at 12 months post-
operatively, as measured by a positive response of > 1 to Question 17 on PFDI-
20. 
 
2. Any retreatment for stress incontinence including pelvic floor physical therapy; 
incontinence pessary; urethral bulking injection; repeat incontinence surgery 
 
 
3. Surgical intervention for urinary retention (sling lysis or revision) at any time point 
post-operatively 
 
Secondary outcome measures will assess the degree to which the study 
intervention influences adverse events intra- and post-operatively and will include 
the following: 
 
1. Adverse events  
 
2. De novo (new affirmative response of > 1 to Question 16 on PFDI-20) or 
worsening urge incontinence symptoms (increase of score on Question 16 by 2 
points or more on PFDI-20) at 12 months post-operatively. 
 
3. Surgeon satisfaction with the sling will be assessed immediately post-
operatively with a 10-point VAS.  
 
4. Patient Global Impression of Improvement (PGI-I) Scale for incontinence 
symptoms.26 
 
5. Need for bladder drainage beyond 6 weeks post-operatively 
 
 
POWER CALCULATION: 
This study is a non-inferiority study design. The null hypothesis is that the 
difference in the proportion of women with abnormal bladder function in the SIS 
group compared to RP sling group is 12% or more (noninferiority margin: H0: RP-
SIS_ 0.12). Based on criteria used in a previously published multicenter trial of 
mid-urethral slings, we chose a noninferiority margin of 12%. Assuming a 
subjective cure rate for RP of 82%,127 individuals in each group will provide 80% 
to reject the null hypothesis (H0) that the true difference in cure rates between the 
two procedures (% cure RP and % cure ALTIS SIS sling) is less than or equal to 
12% in favor of the alternate hypothesis (H1: SIS-RP_ 0.12) that the true difference 

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in proportions is greater than 12% using a two-group large-sample normal 
approximation test of proportions with a one-sided 5% significance level. Assuming 
a 10% loss to follow-up or drop-out rate for the duration of the study, the total 
enrollment goal is 280.  Non-inferiority was declared if the upper bound of the 95% 
confidence interval for the between group difference in bladder function was less 
than 12%.  To minimize bias toward non-inferiority, only women treated per 
protocol (ie: underwent the randomized sling) were considered in the primary 
outcome analysis. A secondary analysis of the primary outcome was performed 
on the intent to treat population.  Likewise, other secondary outcome measures 
were performed on the intent to treat population. 
 
CALENDAR OF EVENTS  
 
 
Baseline Surgery 
Day 
of 
DC 
 
2  
weeks 
 
6 
weeks 
 
6  
months 
 
12 
months 
Informed 
Consent 
X 
 
 
 
 
 
 
CRF 
X 
X 
X 
X 
X 
 
X 
Demographic 
information  
X 
 
 
 
 
 
 
Charlson 
Comorbidity 
Index 
X 
 
 
 
 
 
 
POP-Q 
X 
 
 
 
X 
 
X 
PFDI-20 short 
form 
X 
 
 
 
X 
 
X 
PFIQ -7 short 
form 
X 
 
 
 
 
 
X 
PISQ-IR 
X 
 
 
 
 
 
X 
Quality of Life 
measure (SF-
12) 
X 
 
 
 
 
 
X 
Randomization 
 
X 
 
 
 
 
 
Assessment of 
voiding function 
 
 
X 
X 
X 
 
X 
PGI 
 
 
 
 
X 
 
X 
VAS of Surgeon 
ease of use of 
sling  
 
X 
 
 
 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
 
 

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DATA COLLECTION & MANAGEMENT 
Data collection will occur at each site at each visit outlined in the Calendar of 
Events.  All study data will be recorded on data collection forms provided by the 
coordinating site and securely maintained at each site.  Any discrepancies 
between data collection forms and supporting source documents such as 
physician’s notes should be explained on the forms.  Any changes made to original 
entries on data collection forms should be crossed through with a single line and 
initial and dated by the person making the correction.  Do not obscure the original 
entry.   
Data will be entered by study staff at each site into a REDCap database (described 
in detail in the “STUDY SUBJECT PROTECTION” section of this protocol) that will 
be stored on a secure server by the data coordinating center.  Study data source 
documentation and progress notes will be monitored by the data coordinating 
center as outlined in the “STUDY MONITORING AND DOCUMENTATION” 
section.  Data collected from visits should be entered into REDCap within 5 
business days.  Any queries to data entered into REDCap should be addressed 
within 5 business days.  Each site should regularly check REDCap for queries.   
 
Each site will maintain all essential study documents in original format and source 
documentation that support the data collected on study participants in compliance 
with ICH/GCP guidelines.  Documents must be retained until at least 2 years have 
elapsed since the formal discontinuation of the clinical investigation.  Each site will 
be responsible to ensure that these essential documents are retained and are not 
accidentally damaged or destroyed prior to the required elapsed time.   
 
 
STUDY MONITORING AND DOCUMENTATION 
Study Monitoring 
 
The Principal Investigator at the data coordinating center will monitor the study and 
assess the need for amendments as the study progresses.  If a protocol revision 
is necessary for reasons including but not limited to the rights, safety, or welfare of 
participants, or scientific integrity of the data, an amendment is required.  IRB or 
equivalent approvals of the revised protocol—and if necessary, revised informed 
consent—must be obtained prior to implementation at each site.   
Data Monitoring 
Monitoring will be conducted by the data coordinating center throughout the study 
to ensure that the study is conducted in accordance with the study protocol, Good 
Clinical Practice, and applicable regulations.  By verifying source data, monitoring 

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helps to safeguard subject safety, ensure data quality, and provide ongoing 
training and support to ensure compliance.   
Semi-annual data verification will be conducted by the data coordinating center to 
verify that data entry into REDCap is accurate, and to assess compliance with the 
study protocol requirements.  Study data will be source verified for roughly 25% of 
each site’s over all data collection efforts.  The data coordinating center reserves 
the right to monitor more often or a higher percentage if a problem is identified 
upon verification of the 25%.  Site investigators and study personnel must 
guarantee access to copies of redacted source documents including medical 
records and auxiliary source documents that support progress note entries.  
Requests for de-identified/redacted progress notes and supporting documents 
from each site will be supplied via email at least 10 days prior to the deadline.  
Other monitoring activities include but are not limited to reviewing informed 
consent/research authorization forms, adverse event documentation, and protocol 
deviation reports.  Any action items or data queries generated by the data 
coordinating center after monitoring should be resolved within 5 days.   
In the event that a site is notified of a regulatory inspection, sites should 
immediately contact the data coordinating center (WFBH).  The data coordinating 
center will manage the REDCap database, as well as monitor quality assurance 
for data entered by each site.   
Protocol Deviations 
Protocol deviations must be documented on the protocol deviation CRF provided 
by the coordinating site, logged in each site’s protocol deviation log, and entered 
into REDCap.  Protocol deviations will be documented in sequential order 
according to site—not by individual patient—and they will be entered into 
REDCap.   
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, 
appropriate corrective and preventative actions (including notification, site re-
training, or discontinuation) will be put into place by the principal investigator. 
Site staff must not make any changes or deviate from this protocol, except to 
protect the life and physical well-being of a subject in an emergency. Site staff shall 
notify the PI and the reviewing IRB of any deviation from the investigational plan 
to protect the life or physical well-being of a subject in an emergency, and those 
deviations which affect the scientific integrity of the clinical investigation. Such 
notice shall be given as soon as possible, but no later than 5 working days after 
the emergency occurred.   Local IRB/regulatory requirements will prevail if sooner 
than 5 working days.   All deviations from the investigational plan, with the reason 
for the deviation and the date of occurrence, must be documented and reported to 
the Data Coordinating Center. Study sites may also be required to report 
deviations to their IRB per local guidelines and government regulations.  
 

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18
 
 
Data Safety Monitoring Board 
A data safety monitoring board (DSMB) will be established that is made up of two 
independent physicians with no connection to the conduct of this clinical trial who 
have no relevant conflicts of interests. The PI will review the DINDO grading of any 
sling related  post adverse events within 48 hours of reporting and will immediately 
report these events to the DSMB.  The DSMB will receive a progress report of 
study recruitment, enrollment, and retention every 6 months and make a 
determination regarding appropriate continuation of the study. 
REPORTING ADVERSE EVENTS: 
 
Adverse events will be recorded and reported according to criteria and timeline 
below.  Sites will also follow local regulatory standards for AE reporting.   
 
All study-related AEs must be recorded on the AE CRF supplied by the 
coordinating site, entered into the site AE log, then entered into REDCap.  Each 
AE will be sequentially numbered according to patient.  For example, patient 003’s 
first AE would be 003.01.  Each site investigator will determine the relationship of 
the AE to the operative procedures, the relationship of the AE to the device, along 
with the severity of each reportable AEs. All complications will be evaluated by the 
sub-sites with PI (CAM) being the deciding factor for the DINDO score (See Table 
Below). The sub-sites will also determine if the complications are more likely to be 
related to the overall surgery, sling surgery or both. Complications that are deemed 
not related to the surgery will be excluded (For example, a MI at >3mo postop.) 
 
SAEs must be reported to the DSMB within two business days as outlined above 
in the DSMB section.  
 
TABLE 1. Classification of Surgical Complications Clavien-DINDO Grade 
Definition for Sling attributed post-op events only  
 
Grade 1 
Any deviation from the normal postoperative 
course without the need for pharmacologic 
treatment. Allowed therapeutic interventions 
are: drugs as antiemetics, antipyretics, 
analgesics, physiotherapy 
Grade II 
Requiring pharmacological treatment with 
drugs other than such allowed for grade I 
complications Blood transfusions and total 
parenteral nutrition are also included 
Grade III 
 
Requiring surgical, endoscopic or radiological 
intervention 

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     IIIA 
     IIIB 
 
       Intervention not under general anesthesia 
       Intervention under general anesthesia 
Grade IV 
 
    IVA 
    IVB 
Life-threatening complication (including CNS 
complications)* requiring IC/ICU management   
Single organ dysfunction (including dialysis) 
Multiorgan dysfunction 
Grade V 
 Death 
 
 
Protocol Specific Reportable AEs include those determined to be related to the 
operative procedures or the device as listed below:   
 
Bleeding 
Bladder Injury (Cystotomy or Bladder Trocar Perforation) 
Vaginal Wall Perforation  
Urethral Injury  
Bowel Injury  
Nerve Injury 
Intestinal Injury 
Infection (UTI, Vaginal, Pelvic Abscess) 
Bowel Obstruction  
Venous Thromboembolism  
Mesh Exposure  
Leg Pain or Difficulty Ambulating  
Fistula  
Urinary Retention 
Hematoma 
Bladder Outlet Obstruction 
Urgency “de novo” 
Stress or Urgency Incontinence (New or Worsening) 
Recurrent POP 
Other Urogynecologic Complications: ____________ 
 
Please note that underlying diseases are not reportable as AEs unless there is an 
increase of severity or frequency during the course of the study.  If an AE has not 
resolved at the time of AE Form completion, save form as incomplete in REDCap 
until resolved. Once resolved, update AE form, and enter into REDCap and save 
form as complete.  
Adverse Event Definitions: 
Adverse Event: any untoward medical occurrence, unintended disease or injury, 
or any untoward clinical signs (including abnormal laboratory finding) in subjects, 
whether or not related to the operative procedures  
 

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Serious Adverse Event: an adverse event that:  
  Led to death  
  Led to serious deterioration in the health of the subject that either    resulted 
in  
o a life-threatening illness or injury  
o a permanent impairment of a body structure or a body function  
o in-subject or prolonged hospitalization of existing hospitalization  
o medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body 
function  
 Led to fetal distress, fetal death or a congenital abnormality or birth defect  
 
Relationship of AE to Operative Procedures: 
 
Unrelated: No evidence that the timing if the AE has a relationship to the operative 
procedures performed.  
Possibly Related: The AE has a timely relationship to the operative procedures 
performed, however a potential alternative etiology may be responsible for the AE.  
Probably Related: The AE has a timely relationship to the operative procedures 
performed and the causative relationship can clearly be established. No potential 
alternative etiology is apparent.  
Adverse Event Severity: 
 
Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant 
type causing no loss of time from normal activities. Symptoms do not require 
therapy or a medical evaluation; signs and symptoms are transient. 
 
Moderate: Events introduce a low level of inconvenience or concern to the 
participant and may interfere with daily activities, but are usually improved by 
simple therapeutic measures; moderate experiences may cause some 
interference with functioning. 
 
Severe: Events interrupt the participant’s normal daily activities and generally 
require systemic drug therapy or other treatment; they are usually incapacitating. 
 
 
Relationship of AE to Device:  
Unrelated: No evidence that the timing if the AE has a relationship to the device 
placement.  
Possibly Related: The AE has a timely relationship to the device placement, 
however a potential alternative etiology may be responsible for the AE.  

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Probably Related: The AE has a timely relationship to the device placement 
performed and the causative relationship can clearly be established. No potential 
alternative etiology is apparent.  
 
STUDY SUBJECT PROTECTION 
 
Protection of each subject’s personal health information will be a priority in this 
study. One master Excel file containing subject personal information including 
name and medical record number will be kept in a password-protected file, on a 
designated protected research drive on a password-protected computer in a 
locked office at each respective institution. In that file, each subject will be assigned 
a subject identification number that will be used for the purposes of data collection 
in order to de-identify subjects.  
 
All paper forms used for data collection will be kept in a research cabinet dedicated 
to this project, which will be locked at all times, in a locked office at Wake Forest 
Baptist Health (or other institution). All forms will contain de-identified information 
when sent to the monitoring site. Identification numbers will correspond to the 
subjects listed in the master excel file.  
 
All study data will be transferred and managed electronically using REDCap 
(Research Electronic Data Capture). Each subject will be entered into REDCap 
using the assigned identification number from the master excel file. REDCap is a 
secure, web-based application designed to support data capture for research 
studies, providing user-friendly web-based case report forms, real-time data entry 
validation, audit trials, and a de-identified data export mechanism to common 
statistical packages. The system was developed by a multi-institutional consortium 
that was initiated at Vanderbilt University and includes Wake Forest Baptist Health. 
The database is hosted within the Clinical and Translational Research Unit at 
Wake Forest and is managed by the Quantitative Health Sciences Department. 
The system is protected by a login and Secure Sockets Layers (SSL) encryption. 
Data collection is customized for each study as based on a study-specific data 
dictionary defined by the research team with guidance from the REDCap 
administrator in Quantitative Health Sciences at Wake Forest.  
 
AUTHORSHIP 
 
For the primary paper, Dr. Matthews will serve as first author, Dr. Gutman as 
second author for contributions made to study design and protocol development, 
and Dr. Roovers as senior author for statistical analysis and protocol development. 
All site PIs will be listed as authors, in addition to the top 3 recruiting Co-
Investigators, in order of recruitment volume.  
 
All investigators will have equal access to the primary data set for secondary 
analyses.  A research design will have to be submitted to the study PI to ensure 
no duplication of effort. For any secondary analyses, Dr. Matthews will serve as 

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the senior author and only those members of the group involved in the secondary 
analysis will be listed as authors on any subsequent papers. 
 
 
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