CREDE Study: Intraoperative Crede Manoeuver Compared to Preoperative Prolapse Reduction Stress Test to Predict Postoperative de Novo Stress Urinary Incontinence (PONSUI) at the Time of Pelvic Organ Prolapse (POP) Surgery
CREDE Study: Intraoperative Crede Manoeuver Compared to Preoperative Prolapse Reduction Stress Test to Predict Postoperative de Novo Stress Urinary Incontinence (PONSUI) at the Time of Pelvic Organ Prolapse (POP) Surgery
The CREDE pilot randomized study will compare the intraoperative Crede manoeuver (M1) to
 preoperative prolapse (POP) reduction cough stress test (M2) for the prediction and
 prevention of PONSUI. The rates of PONSUI and its effect on patient reported outcomes and
 quality of life will be determined among women with positive or negative tests, and those
 with and without concomitant sling placed. This information will help inform larger studies
 on the topic.
Primary objective

 -  To assess feasibility of a pilot study to test this hypothesis with the goal to conduct
 a full trial (sample size calculation, validation of instruments used, randomization
 processes)

 -  To estimate the rate of subjective PONSUI at 6 weeks and at 6 months in continent women
 undergoing POP surgical repair where a positive intraoperative Crede maneuver (M1) vs. a
 positive preoperative prolapse reduction stress test (M2) are used to select candidates
 for concomitant retropubic midurethral sling (MUS)

 Secondary objectives

 I. To compare the estimated rate of objective PONSUI at 6 weeks and at 6 months (as
 determined by cough stress test) in continent women undergoing POP surgical repair where a
 positive intraoperative Crede maneuver (M1) vs. a positive preoperative prolapse reduction
 stress test (M2) are used to select candidates for concomitant retropubic midurethral sling
 (MUS) II. To compare the rate of urinary symptoms and the effect on quality of life at 6
 weeks and 6 months between M1 and M2, by Urinary Distress Inventory (UDI-6) and Urinary
 Impact Questionnaire (UIQ-7) III. To describe the risk of complications in patients having
 either maneuvers (M1, M2), including bladder perforation, voiding dysfunction, urinary tract
 infection and mesh exposure IV. To assess the concordance/discordance rate of M1 and M2 to
 compare the predictive subjective and objective PONSUI values of both maneuvers by test
 results and by anti-incontinence surgery

 Methodology

 This is a pilot randomized controlled study of two parallel groups, in a sample of 110
 continent women undergoing surgical correction of symptomatic pelvic organ prolapse (POP).
 The sample will be drawn from women presenting to three urogynecologists in at St-Mary's
 hospital and McGill University Health Center (MUHC). W

 Intervention:

 The patients will be randomized in two groups, allocated in a 1:1 ratio. All participants
 will undergo both methods to evaluate their risk of PONSUI. Method 1 (M1) consists in
 intraoperative Crede maneuver. Method 2 (M2) consists in a preoperative prolapse reduction
 stress test. In group A: A positive M1 will determine placement of MUS. In group B: A
 positive M2 will determine placement of MUS.

 Surgical Procedure In both groups, women will have their planned surgery for POP correction
 under spinal (regional) or general anesthesia. The POP repair followed by the M1 will be
 performed for all women. The result of preoperative M2 won't be available to surgeon at the
 moment of performing M1. If the PONSUI prediction test for which the patient had been
 randomized to is positive, we will place a midurethral sling (MUS) after the POP repair.
 Specifically, we will place a retropubic tension-free vaginal tape (TVT) MUS, as those slings
 are associated with excellent cure rate (71-97%) and are most commonly used by
 urogynecologists at our institution. Placement of MUS will follow standardized reported
 technique. After the surgical procedure, a Foley catheter will be inserted, and removed on
 postoperative day one. After catheter removal, a trial of void protocol is in place at our
 institutions. If post void residual volume by bladder scanner is over 250 mL, the Foley
 catheter will be reinserted and left in place for one week, while prophylactic antibiotics
 are given.

 Randomization:

 To address potential imbalances across study groups a computer-generated (SAS version 9.4)
 randomization schedule will be stratified by recruitment site (2 different recruitment
 clinics) and prolapse stage (II vs. III-IV), using random block sizes of 2 or 4, with an
 allocation ratio of 1:1. In order to ensure allocation concealment, the research assistant
 will first verify eligibility and informed consent, and then assign a study ID to each
 participant. Prior to the surgical procedure, the research assistant will enter this
 information plus the recruitment site and prolapse stage into an automated interface prepared
 by the statistician. The result of randomization will be available to the surgeon only in the
 operating room (OR), after both the preoperative M2 and the intraoperative M1 have been
 performed. Specifically, the primary surgeon will be blinded until immediately after the M1
 is performed and the result is recorded. The research assistant will have left an envelope
 with the randomization group in the OR prior to the beginning of the procedure. This envelope
 will be opened after the M1 is performed. The result of M2 will also be available if the
 woman is randomized to group B.

 Sample size consideration:

 Approximately 200 patients undergo POP surgical repair surgery per year in the two centers
 where the study will be conducted. For the pilot study, we are planning to recruit 100
 eligible patients (50 per group) into the study with an added 10% estimated dropout rate for
 an overall total of 110 patients (55 per group). To the best of our knowledge, no previous
 study exists which would allow us to perform the appropriate sample size calculations. To do
 so, we would need some estimate of the rate of subjective PONSUI after intraoperative Crede
 maneuver (M1) at 6 weeks and 6 months. It is one of the purposes of this pilot project to
 determine such a parameter for planning a future randomized controlled trial. The rate of
 subjective PONSUI after preoperative prolapse reduction stress test (M2) varies around 14%,
 54%, 17%, 26% for positive tests with and without anti-incontinence surgery and for negative
 tests with and without anti-incontinence surgery respectively. We thus estimate an overall
 rate of 30% PONSUI with the use of the preoperative prolapse reduction stress test. In the
 absence of an educated guess, we have verified that with our sample size (50 in each group)
 the minimal significant difference of 22% (30% vs 8%) between two groups PONSUI rates could
 be detected with a power of at least 80% using Pearson chi-squared and a confidence level of
 α = 0.05. Also, a set of relevant baseline imbalances will be pre-specified (recruitment site
 and prolapse stage "II vs III-IV") and a stratified randomization will be performed.

 Data gathering Variables collected will include age, medication (including hormonal therapy),
 smoking status, diabetes, past obstetrical history (including parity, vaginal deliveries and
 cesarean sections), previous surgery for POP (type), previous hysterectomy, menopausal
 status, daytime frequency and nocturia. Patient will also answer validated questionnaires on
 urinary symptoms and impact on quality of life including: 1. Urinary Distress Inventory
 (UDI-6), and 2. Urinary Impact Questionnaire (UIQ-7).

 At baseline, physical examination will be performed by one of the three participating
 urogynecologists or one of the urogynecology fellows. It will include POP-Q evaluation,
 genitourinary atrophy assessment, myofascial pain (pain at palpation of the vaginal muscles),
 and the preoperative prolapse reduction stress test (M2) for all women (positive/negative).
 After the exam, women will be asked to urinate and we will estimate the post void residual
 volume (urine left into the bladder after a micturition) with a bladder scanner.

 At the moment of the surgery to correct the POP, all of the women will have a Crede maneuver
 assessment (M1). The result of the test will be noted (positive/negative). Information
 collected at the time of the surgery will include date, type of surgery, type of anesthesia
 (general or regional), estimated blood loss, perioperative complications (as bladder and
 urethral perforation or hemorrhage). Postoperative complications such as postoperative
 urinary retention (use of Foley catheter for seven days or more), and urinary tract infection
 will also be recorded.

 Women will follow the usual postoperative visit calendar used in our institutions (visit 6
 weeks and 6 months after the surgery). They will fill the same two questionnaires (UDI-6 and
 UIQ-7) that they answered at the beginning of the study. A blinded urogynecologist or a
 fellow in urogynecology will perform an examination. The amount of urine into the bladder
 will be estimated with a bladder scanner. A cough stress test will be done with an amount
 estimated between 250-350 mL of urine. The patient will be asked to drink water if the
 bladder is not full enough. The women have to cough strongly while in supine position. The
 examiner will note if he sees urine leakage (positive test) or not (negative test). He/she
 will also do a vaginal examination to note prolapse stage (POP-Q), and if there are any
 complication including mesh erosion or extrusion and important pain.

 The research assistant will be involved at the time of women's recruitment, to ensure patient
 randomization, to coordinate postoperative examinations by a blinded examiner, and for data
 collection.
Inclusion Criteria:

 -  Anterior, uterine or apical prolapse with a POP-Q stage II or more requiring surgical
 correction

 Exclusion Criteria:

 -  Stress urinary incontinence (SUI) on history

 -  Previous anti-incontinence surgery

 -  Pregnancy

 -  Prior urethral repair surgery (diverticulum, fistula)

 -  Women declining the use of any mesh product or a mid-urethral sling procedure

 -  Absolute contraindication to MUS (pelvic kidney, vascular graft, low ventral hernias)

 -  Women who do not speak or read English or French

 -  Isolated posterior compartment prolapse

 -  Geographic location preventing women to come to 6 week and 6 month appointments