Randomized Controlled Trial of Cystocele Plication Risks ("CPR Trial"): A Pilot Study
Condition: Voiding Dysfunction
MeSH terms: Cystocele
Study type: Interventional
Phase: Phase 2

Summary: 
      Up to 50% of patients undergoing pelvic floor repair experience short-term postoperative
      voiding dysfunction, increasing the length of hospitalization, cost and anxiety among
      patients.

      The mechanism behind this problem is the sutures placed in the pubocervical fascia during the
      cystocele repair. The cited benefit of bladder plication is greater cure of cystocele. The
      existence of pubocervical fascia and the need for placement of plicating sutures over the
      bladder have been questioned.

      The objective of this study is to determine if avoiding cystocele plication in women
      undergoing surgery for cystocele decreases the need of catheterization beyond post operative
      day #2.

      We will conduct a RCT of patients undergoing transvaginal repair of midline cystocele at the
      Mount Sinai Hospital. Patients will be randomized to receiving plicating sutures versus no
      plication. This procedure may be conducted with or without concomitant correction of other
      sites of prolapse. However, they will not have any procedures for correction of stress
      incontinence.

      This study will be powered to detect a reduction in voiding dysfunction from 50% to 25% of
      patients. Using a χ2 distribution, and an alpha error of 0.05, the required sample size is 58
      patients per group.
    

Detailed description: 
      Vaginal prolapse is a common problem in women. Approximately 11% of women undergo pelvic
      reconstructive surgery for either pelvic organ prolapse and/or urinary incontinence[1].
      Several surgical techniques for correction of prolapse have evolved and have been
      scientifically evaluated. However, many basic surgical gynecological principles and
      techniques have been passed on over generations without any scientific evaluation. The
      technique of transvaginal repair of cystocele due to an anterior midline defect has
      traditionally included four steps: 1. mobilization of the defect (i.e. separation of vagina
      from bladder); 2. reduction of the defect (i.e. placement of plicating sutures into the
      pubocervical fascia); 3. trimming of redundant vaginal tissues; and 4. reapproximating the
      vaginal mucosa[2, 3]. Although each surgeon may modify any of these steps (ex. Depth of
      dissection, location and number of sutures), the principles are consistent. The existence of
      pubocervical fascia and the need for placement of plicating sutures over the bladder have
      been questioned, and some vaginal surgeons omit this step[4-6]. The cited benefit of bladder
      plication is greater cure of cystocele. Some of the potential risks of plication include
      ureteric obstruction, if the sutures are near the ureteric orifice, and voiding dysfunction
      if the sutures are near the urethrovesical junction[3, 7]. A chart review of patients at the
      Mount Sinai Hospital, who underwent typical pelvic floor repair, including transvaginal
      cystocele repair and mid-urethral sling, has shown that approximately 50% of patients
      experience short-term postoperative voiding dysfunction (non-published data), increasing the
      length of hospitalization, cost and anxiety among patients.

      This pilot trial will assess the short-term risks of cystocele plication, and will assess
      trial feasibility. Ideally a larger subsequent trial will assess the cure of cystocele one
      year after surgery. To the best of my knowledge, this is the first study to assess the
      short-term post-operative outcomes in women who undergo this procedure.

      3- Research Question In women with cystocele due to an anterior midline defect, does
      cystocele plication (independent variable) result in more or less patients requiring
      catheterization beyond postoperative day 2 (dependent variable) compared to no plication?

      Hypothesis The hypothesis is that there may be more short-term voiding dysfunction and
      ureteric obstruction following cystocele repair with plication than following cystocele
      repair without plication.

      4- Population of Interest and Sampling Methods Inclusion criteria: Patients between 18 and 75
      years, who will undergo surgery at the Mount Sinai Hospital that includes cystocele repair,
      will be eligible.

      Exclusion criteria: Patients will be excluded if the surgeon places anterior vaginal mesh or
      a mid-urethral sling, and/or if they had prior surgery for anterior vaginal wall prolapse
      and/or stress urinary incontinence.

      Recruitment strategy: The patients will be recruited at the Mount Sinai Hospital
      Urogynecology Department. Approximately 4 to 6 eligible patients are seen per week and it is
      estimated that at least one patient will be recruited per week. The study will be completed
      in approximately two years. This will be a single centre study conducted at the Mount Sinai
      Hospital, Toronto, Canada.

      5- Manoeuvre Study Design This study is a double blind, randomized controlled trial of
      patients undergoing transvaginal repair of midline cystocele, with or without concomitant
      correction of prolapse in other vaginal compartments, but without correction of stress
      incontinence. All the patients will provide written informed consent for participation. At
      baseline, all participants will undergo a standardized evaluation, which will include an
      urogynecologic history, pelvic organ prolapse quantification examination, and urodynamic
      evaluation. The urodynamic evaluation will include measurement of post-void residual urine
      volume by catheter and/or ultrasound bladder scan, uroflowmetry, a filling cystometrogram and
      urethral pressure profilometry.

      Patients will be randomized intraoperatively using computer-based randomization. At the time
      of the surgical step of bladder plication, the computer program will be used, and will
      indicate whether sutures will be placed or omitted. Trimming of redundant vaginal mucosa will
      be performed before randomization to avoid any bias resulting from the amount of mucosa
      removed.

      Standardized surgical technique

        -  Midline vaginal mucosal incision

        -  Sharp surgical dissection between vagina and pubocervical fascia.

        -  Completion of prolapse repair of vault, rectocele, uterine prolapse.

        -  Manual reduction of prolapse and trimming of redundant vaginal mucosa.

        -  Open envelope to determine group of allocation.

        -  If randomization to plication, place midline interrupted sutures of 0 or 2-0
           polyglycolic acid sutures.

        -  Administer indigo carmine 5 ml IV.

        -  Cystoscopy with 70º telescopes.

        -  Close vaginal mucosa with running interlocking 0 or 2-0 polyglycolic sutures.

      Protocol On postoperative day 1, patients will have the Foley catheter removed and
      measurement of post-void residual urine volume will be done (either by in and out
      catheterization, suprapubic ultrasound or via a Bonnano suprapubic catheter). Catheterization
      will be continued until residual volumes are less than 200 ml twice in a row. Registered
      nurses who will be masked to the treatment assignment will perform the post-operative
      assessment and examination.

      6- Outcomes Primary Outcome Measures The primary outcome variable will be the requirement for
      catheterization beyond postoperative day 2. This has been chosen as the primary outcome since
      this would delay the usual hospital discharge on postoperative day 2, thus presenting a
      practical problem for patients (important based in our patients value and expectative after
      pelvic organ prolapse surgery), physicians, and hospitals (cost).

      Other Outcome Measures A secondary outcome will be intraoperative ureteric obstruction. All
      patients, regardless of study arm, will undergo intraoperative cystoscopy following
      intravenous administration of indigo carmine in order to identify this complication. If this
      complication does occur the suspected plicating suture(s) will removed, replaced more
      centrally, and cystoscopy repeated to ensure ureteric permeability.

      Analysis Sample Size A chart review of patients at the Mount Sinai Hospital, who underwent
      typical pelvic floor repair, including transvaginal cystocele repair and mid-urethral sling,
      has shown that approximately 50% of patients experience short-term postoperative voiding
      dysfunction. In order to provide convincing evidence that there may be a benefit to omitting
      plicating sutures, this study will be powered to detect a substantial difference in voiding
      dysfunction - from 50% of patients down to 25% of patients. Using a chi-square distribution
      and an alpha error of 0.05, the required sample size is 58 patients per group. (SAS 9.2)

      Statistical Analysis Statistical analysis will be performed using SAS 9.2 for Windows™.
      Chi-square analysis will be used to evaluate categorical variables and T-Tests for continuous
      variables.

      Data Management The data will be collected into a database. Statistical analysis will be
      conducted using SAS 9.2. All data will be kept confidential and protected.

      Ethical Issues Written consent will be obtained from each participant. All data will be
      anonymous and will only be coded by a participant identification number.

      An ethics proposal will be submitted to the Mount Sinai Hospital Research Ethics Board prior
      to beginning the recruitment. Patients with questions or concerns are free to contact the
      research assistant or a representative from the ethics board for clarification. The contact
      information will be noted in the consent form.
    

Intervention name(s): Cystocele plication; No Plication
Intervention type(s): Procedure; Procedure
Intervention description(s): placement of sutures over the pubocervical fascia during the cystocele repair; Avoid sutures over pubocervical fascia during cystocele plication
Other intervention name(s): Cystocele reduction; No plicating sutures
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cystocele; voiding; dysfunction