<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04478747</url>
  </required_header>
  <id_info>
    <org_study_id>01072020</org_study_id>
    <nct_id>NCT04478747</nct_id>
  </id_info>
  <brief_title>Transvaginal Mesh vs. Laparoscopic Colposacropexy- Study</brief_title>
  <acronym>TVM vs LCSP</acronym>
  <official_title>Women's Apical Pelvic Organ Prolapse Treatment - a Randomized Controlled Trial Comparing Transvaginal and Laparoscopic Mesh Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helsinki University Central Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helsinki University Central Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of the study is to compare subjective efficacy of trans vaginal mesh and&#xD;
      laparoscopic colposakropexy (CSP) in women with an apical prolapse. The CSP group is further&#xD;
      divided into two sub-groups; one where the mesh fixation is only at the apical part of the&#xD;
      vagina, and another where the fixation is also extended to the levator plane.&#xD;
&#xD;
      The secondary outcomes are safety (peri- and post-surgery complications, pain, erosion),&#xD;
      objective efficacy (simplified POP-Q), and re-operation rate. Subjective outcome also&#xD;
      includes the assessment of sexual satisfaction. Cost-effectiveness is studied by comparing&#xD;
      both direct costs and QALYs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pelvic organ prolapse (POP) is defined as an anatomical support defect of the pelvic viscera.&#xD;
      Women's POP is the descent of uterus or vaginal apex with or without concomitant descent of&#xD;
      the anterior (cystocele) or posterior (rectocele) vaginal wall. It is estimated that the&#xD;
      lifetime risk of POP surgery in women is approximately 10-13%, the incidence peak being 20-30&#xD;
      years after the first delivery, which is also the most important risk factor for POP. Other&#xD;
      risk factors include previous hysterectomy, obesity and genetic factors.&#xD;
&#xD;
      The typical POP symptoms are a feeling of bulge, accompanied with urinary incontinence,&#xD;
      defecation problems, and sexual dissatisfaction. First line treatments are conservative, but&#xD;
      if they fail, surgery is indicated.&#xD;
&#xD;
      Native tissue repair of the anterior and / or posterior vaginal wall (colporrhaphy anterior /&#xD;
      posterior) is commonly the first-line operation. The possible concomitant apical prolapse&#xD;
      needs to be suspended which is typically done by either by performing a hysterectomy with&#xD;
      shortening and suspension of the sacrouterine ligaments, or by amputation of the cervix with&#xD;
      suspension of the cardinale and sacrouterine ligaments (Manchester operation). An unsuspended&#xD;
      apical defect will double the relapse rate (20 vs 11%). In most of the apical recurrences&#xD;
      mesh is used to achieve sufficient support. The re-operation rate of any POP in Finland is&#xD;
      10.8% .&#xD;
&#xD;
      In mesh operations the apex can be suspended either transvaginally (TVM) by anchoring the&#xD;
      mesh to the sacrospinosus ligaments, or by doing a colposacropexy (CSP) where the mesh is&#xD;
      attached to the sacrum, mostly via laparoscopy. The CSP techniques vary e.g. the mesh can be&#xD;
      attached only apically or also to the levator plane. If needed, colporrhaphies can be done&#xD;
      concomitantly.&#xD;
&#xD;
      The use of TVM has decreased due to the FDA-warnings and litigations concerning mainly the&#xD;
      risks of erosion and pain. This has lead to withdrawals of mesh products, despite&#xD;
      well-conducted clinical studies indicating that in well-chosen women light-weight small TVM&#xD;
      is not associated with major complications. Currently, no TVM with good quality clinical data&#xD;
      is available. Traditionally, CSP has been considered safer than TVM in regard of erosions and&#xD;
      pain, but the data is scarce. Furthermore, CSP has a longer learning-curve and is a more&#xD;
      time-consuming operation than TVM, whereas hospital stay is shorter.&#xD;
&#xD;
      To the investigators knowledge, there is only one published study where TVM and CSP has been&#xD;
      compared, and in that study a large &quot;covering&quot; TVM was used which was thereafter withdrawn&#xD;
      from the market. In addition,in most studies, operation techniques, especially with CSP are&#xD;
      not standardized. Therefore, further head-to-head comparisons are needed. The investigators&#xD;
      propose a study comparing efficacy and safety when using the TVM or CSP approach in women&#xD;
      with an apical defect. The investigators will also evaluate whether, in CSP, apical fixation&#xD;
      alone is sufficient, or whether levator plane fixation provide a better outcome.&#xD;
&#xD;
      Study objective:&#xD;
&#xD;
      The main objective of the study is to compare subjective efficacy (PFDI-20, question nro 3;&#xD;
      feeling of bulge) between TVM and CSP in women with an apical prolapse. The CSP group is&#xD;
      further divided into two sub-groups; one where the mesh fixation is only at the apical part&#xD;
      of the vagina, and another where the fixation is also extended to the levator plane.&#xD;
&#xD;
      The secondary outcomes are safety (peri- and post-surgery complications, pain, erosion),&#xD;
      objective efficacy (simplified POP-Q), and re-operation rate. Subjective outcome also&#xD;
      includes the assessment of sexual satisfaction. Cost-effectiveness is studied by comparing&#xD;
      both direct costs and QALYs.&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      Age over 18 years and capability to understand the study protocol either in Finnish or&#xD;
      Swedish.&#xD;
&#xD;
      Objectively diagnosed symptomatic apical prolapse (leading apical prolapse (points C/D ≥-2)&#xD;
      and a history of previous POP operation including hysterectomy.&#xD;
&#xD;
      No need for any other concomitant operations except colporrhaphies and possible prophylactic&#xD;
      salpingo-oophorectomy in CSP groups&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
      A history of previous serious or prolonged pain after any operation. Regular use of systemic&#xD;
      corticosteroid medication. Incapability to understand the study protocol.&#xD;
&#xD;
      Groups, procedures, and randomization:&#xD;
&#xD;
      The participants are randomized into three groups:&#xD;
&#xD;
        1. Transvaginal mesh: BSC mesh (A.M.I., Feldkirch, Austria) is attached to the sacrospinous&#xD;
           ligaments and to the apical part of the vagina. Briefly, 0,25% Lidocain solution with&#xD;
           adrenaline is injected to the anterior vaginal wall and towards the sacrospinous&#xD;
           ligaments bilaterally to reduce bleeding and aid dissection. A vertical incision to the&#xD;
           anterior vaginal wall is done from a point below the bladder neck to approximately 1cm&#xD;
           from the vaginal apex. A full-thickness blunt dissection is done leaving the vaginal&#xD;
           fascia laterally, with tunneling to the sacrospinous ligaments. The two arms of the mesh&#xD;
           are attached with an i-Stich instrument (A.M.I.) to the sacrospinous ligaments 1-2 cm&#xD;
           laterally from the ischial spines. The anterior edge of the mesh is attached to the&#xD;
           vaginal fascia with three Monocryl 3-0 sutures. If needed, the mesh may be shortened in&#xD;
           length and is so, the removed piece is measured and recorded. The arms of the mesh are&#xD;
           set to the stage that the vaginal wall is reduced to its natural position. Complete&#xD;
           vaginal wound closure is done with Vicryl 3-0 sutures. A roll of vaginal gauze for&#xD;
           compression is applied and foley catheter inserted until the following morning. A single&#xD;
           i.v. dose of 1.5g cefuroxime antibiotic is given at the time of anesthesia induction.&#xD;
&#xD;
        2. Colposacropexy with the apical fixation only: EndoGYNious (A.M.I., Feldkirch, Austria)&#xD;
           CSP mesh is attached laparoscopically to the apical part of the vagina. Briefly, a&#xD;
           single i.v. dose 1.5 g of cefuroxime is administered at the time of the anesthesia&#xD;
           induction. The umbilical entry is done optically by a 11 mm trocar and a&#xD;
           pneumoperitoneum up to 12 mmHg is created (then lowered to 8 mmHg, if possible, after&#xD;
           all trocars are inserted). A five mm trocar is placed to the left lower abdomen, a 11 mm&#xD;
           trocar on the left side superior to the previous and a 7.5 mm Airseal trocar to the&#xD;
           right lower abdomen. The promontory is visualized and the avascular space is dissected&#xD;
           by an advanced energy instrument (Thunderbeat, Olympus). The right ureter, the major&#xD;
           vessels and the right hypogastric nerve trunk are identified and avoided during the&#xD;
           dissection. Opening of the right pelvic peritoneum is done with dissection of the&#xD;
           pararectal space. The posterior vaginal peritoneum is opened below the level of the&#xD;
           insertions of the uterosacral ligaments (USL) and the opening is extended to the&#xD;
           peritoneum over the left pararectal area. The rectovaginal and the left pararectal&#xD;
           spaces are dissected to create a posterior peritoneal flap. Anteriorly, the peritoneum&#xD;
           below the vaginal apex is opened and dissected to create an anterior peritoneal flap. A&#xD;
           CSP mesh is fixed to the vaginal apex with five non-absorbable Surgilon 2-0 sutures&#xD;
           utilizing an extracorporeal knot-tying technique: three in a row to the apex and two to&#xD;
           the sides two centimeters posterior to the apex (or alternatively three sutures to the&#xD;
           cervix if it is present). A vaginal speculum examination is performed and any sutures&#xD;
           penetrating the vaginal mucosa are removed and replaced with new ones. The tension of&#xD;
           the mesh is controlled visually via a speculum examination. Anterior and/or posterior&#xD;
           colporraphy is introduced at this point if a vaginal wall prolapse exceeding -2 position&#xD;
           is seen after tensioning the mesh. The mesh is attached to the promontory with five&#xD;
           fasteners (CapSure, Bard). The peritoneum is closed by a running V-Loc Colposacropexy&#xD;
           with apical and levator fixation: EndoGYNious (A.M.I., Feldkirch, Austria) CSP mesh is&#xD;
           attached via laparoscopy to the apical part of the vagina with fixation reaching to the&#xD;
           level of levator plane.&#xD;
&#xD;
        3. Colposacropexy with the apical and the levator fixation: EndoGYNious (A.M.I., Feldkirch,&#xD;
           Austria) CSP mesh is attached laparoscopically to the apical part of the vagina with&#xD;
           fixation reaching to the level of the levator planes. Briefly, the technique is similar&#xD;
           to the apical fixation with the following exceptions: the pararectal spaces are&#xD;
           dissected deep to the level of the levator ani muscles and the CSP mesh is fixed with 11&#xD;
           sutures (figure) (two to the levator ani muscles, two to the insertions of the USLs and&#xD;
           two to the midline of the posterior vaginal wall; the apical fixation is done similar to&#xD;
           the former group).&#xD;
&#xD;
      In all groups concomitant colporrhaphies can be conducted. Anterior or posterior colporraphy&#xD;
      is done in the following fashion: a 0,25% lidocaine solution containing adrenaline is&#xD;
      injected under the anterior or posterior vaginal wall to provide haemostasis and&#xD;
      hydrodissection. The vaginal wall is incised and the fascia is separated from the vaginal&#xD;
      epithelium using a combination of sharp and blunt dissection. The fascia is plicated using a&#xD;
      running 3-0 PDS suture in two layers. Excess vaginal epithelium is excised and the vaginal&#xD;
      epithelium is closed with a running 3-0 Vicryl suture.&#xD;
&#xD;
      All the operators have conducted at least ten surgeries with the mesh before taking part into&#xD;
      the study.&#xD;
&#xD;
      Power calculation:&#xD;
&#xD;
      The primary outcome is subjective success; defined as the absence of vaginal bulge, i.e.&#xD;
      negative response to PDFI-20, question 3 at one-year following the surgery. Previous&#xD;
      literature show various results. Altman et al (NEJM 2011) described that this outcome was&#xD;
      achieved in 61% of women following a transvaginal mesh surgery. A prospective study by Duraes&#xD;
      et al (2019) and Wei et al described an even higher success of 92% to 94%. Laparoscopic CSP&#xD;
      has shown a subjective success rate of 91% to 94%. Based on these findings we assumed that&#xD;
      the subjective success would be 80% following laparoscopic CSP and 75% following a TVM. The&#xD;
      TVM operation is the study population that is compared to the laparoscopic CSP performed in&#xD;
      two different technique (see methods).&#xD;
&#xD;
      The statistical power is based on a non-inferiority assumption with a binary outcome. On the&#xD;
      basis of previous studies we estimated that 96 patients are needed in each group for 80%&#xD;
      power to detect a 20% difference in the primary outcome measure, with a two-tailed error of&#xD;
      1%.&#xD;
&#xD;
      A drop-out ratio of 10% is assumed and 106 women are needed in each group (transvaginal mesh,&#xD;
      laparoscopic colposacropexy type A and laparoscopic colposarcopexy type B). Thus, a total of&#xD;
      318 women are planned to be randomized for the study.&#xD;
&#xD;
      Subjective outcome:&#xD;
&#xD;
      Symptom spesific: Pelvic floor Distress Inventory (PFDI-20), Pelvic floor Impact&#xD;
      Questionnaire (PFIQ), Pelvic Organ Prolapse / Urinary Incontinence Sexual Questionnaire&#xD;
      (PISQ-12) Overall quality of life: 15D and RAND-36 questionnaires Pain is evaluated by visual&#xD;
      analogue scale (VAS; 0-10) scale. The questionnaires are filled preoperatively, and after 6&#xD;
      months, 12 months, and 5 years.&#xD;
&#xD;
      Objective outcome:&#xD;
&#xD;
      Evaluation of the leading part of the apical point, and anterior and posterior vaginal walls&#xD;
      (cm in relation to the hymen level) preoperatively, and after 6 months, 12 months, and 5&#xD;
      years.&#xD;
&#xD;
      Peri- and postoperative (both short- and long-term) complications and possible re-operations&#xD;
      are recorded and classified according to the Claviend-Dindo.&#xD;
&#xD;
      Operation time, hospital stay, length of sick leave and costs of medications for operation&#xD;
      and possible complications are recorded.&#xD;
&#xD;
      Cost-effectiveness:&#xD;
&#xD;
      Direct and indirect costs cover length of operation time, length of hospital stay, needed&#xD;
      pain medication at home, other needed medication, length of sick leave, costs of possible&#xD;
      further outpatient department visits or hospital stay with possible re-operations.&#xD;
&#xD;
      QALY calculations are based on 15D and RAND-36 questionnaires.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 2027</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Subjective success; defined as the absence of vaginal bulge</measure>
    <time_frame>5 years</time_frame>
    <description>Negative response to PDFI-20, question 3, at one-year following the surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peri and post-operative complications</measure>
    <time_frame>1 year</time_frame>
    <description>peri- and post-operative complications as recorded in medical charts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative pain</measure>
    <time_frame>1 year</time_frame>
    <description>Pain is evaluated by visual analogue scale (VAS; 0-10) scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective efficacy</measure>
    <time_frame>1 year</time_frame>
    <description>simplified POP-Q</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-operation rate</measure>
    <time_frame>1 year</time_frame>
    <description>re-operations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>1 year</time_frame>
    <description>Studied by comparing both direct costs and QALYs.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">318</enrollment>
  <condition>Prolapse, Vaginal Vault</condition>
  <arm_group>
    <arm_group_label>Transvaginal mesh</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>BSC mesh (A.M.I., Feldkirch, Austria) is attached to the sacrospinosus ligaments and to the apical part of the vagina.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Colposacropexy with the apical fixation only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EndoGYNious (A.M.I.) CSP mesh is attached laparoscopically to the apical part of the vagina.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Colposacropexy with the apical and the levator fixation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EndoGYNious (A.M.I.) CSP mesh is attached laparoscopically to the apical part of the vagina with fixation reaching to the level of the levator planes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>TVM</intervention_name>
    <description>Transvaginal mesh operation using BSC mesh (A.M.I., Feldkirch, Austria)</description>
    <arm_group_label>Transvaginal mesh</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Colposacropexy</intervention_name>
    <description>Colposacropexy using EndoGYNious mesh (A.M.I., Feldkirch, Austria)</description>
    <arm_group_label>Colposacropexy with the apical and the levator fixation</arm_group_label>
    <arm_group_label>Colposacropexy with the apical fixation only</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age over 18 years and capability to understand the study protocol either in Finnish or&#xD;
             Swedish.&#xD;
&#xD;
          -  Objectively diagnosed symptomatic apical prolapse (leading apical prolapse (points&#xD;
             C/D) ≥ -2) and a history of previous POP operation including hysterectomy.&#xD;
&#xD;
          -  No need for any other concomitant operations except colporrhaphies and possible&#xD;
             prophylactic salpingo-oophorectomy in CSP groups&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of serious or prolonged pain after any operation or current or previous&#xD;
             prolonged (over 6 months) pain of any reason.&#xD;
&#xD;
          -  BMI over 40&#xD;
&#xD;
          -  Regular use of systemic corticosteroid medication.&#xD;
&#xD;
          -  Incapability to understand the study protocol.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Tomi Mikkola, Prof.</last_name>
    <phone>+358504271187</phone>
    <email>tomi.mikkola@hus.fi</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Camilla Isaksson, MD</last_name>
    <email>camilla.isaksson@hus.fi</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Helsinki Naistenklinikka</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Camilla Isaksson, Senior consultant</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>March 20, 2023</last_update_submitted>
  <last_update_submitted_qc>March 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Camilla Isaksson</investigator_full_name>
    <investigator_title>Senior consultant</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Prolapse</mesh_term>
    <mesh_term>Prolapse</mesh_term>
    <mesh_term>Pelvic Organ Prolapse</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04478747
org study id: 01072020
nct id: NCT04478747
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of the study is to compare subjective efficacy of trans vaginal mesh and
      laparoscopic colposakropexy (CSP) in women with an apical prolapse. The CSP group is further
      divided into two sub-groups; one where the mesh fixation is only at the apical part of the
      vagina, and another where the fixation is also extended to the levator plane.

      The secondary outcomes are safety (peri- and post-surgery complications, pain, erosion),
      objective efficacy (simplified POP-Q), and re-operation rate. Subjective outcome also
      includes the assessment of sexual satisfaction. Cost-effectiveness is studied by comparing
      both direct costs and QALYs.
Pelvic organ prolapse (POP) is defined as an anatomical support defect of the pelvic viscera.
      Women's POP is the descent of uterus or vaginal apex with or without concomitant descent of
      the anterior (cystocele) or posterior (rectocele) vaginal wall. It is estimated that the
      lifetime risk of POP surgery in women is approximately 10-13%, the incidence peak being 20-30
      years after the first delivery, which is also the most important risk factor for POP. Other
      risk factors include previous hysterectomy, obesity and genetic factors.

      The typical POP symptoms are a feeling of bulge, accompanied with urinary incontinence,
      defecation problems, and sexual dissatisfaction. First line treatments are conservative, but
      if they fail, surgery is indicated.

      Native tissue repair of the anterior and / or posterior vaginal wall (colporrhaphy anterior /
      posterior) is commonly the first-line operation. The possible concomitant apical prolapse
      needs to be suspended which is typically done by either by performing a hysterectomy with
      shortening and suspension of the sacrouterine ligaments, or by amputation of the cervix with
      suspension of the cardinale and sacrouterine ligaments (Manchester operation). An unsuspended
      apical defect will double the relapse rate (20 vs 11%). In most of the apical recurrences
      mesh is used to achieve sufficient support. The re-operation rate of any POP in Finland is
      10.8% .

      In mesh operations the apex can be suspended either transvaginally (TVM) by anchoring the
      mesh to the sacrospinosus ligaments, or by doing a colposacropexy (CSP) where the mesh is
      attached to the sacrum, mostly via laparoscopy. The CSP techniques vary e.g. the mesh can be
      attached only apically or also to the levator plane. If needed, colporrhaphies can be done
      concomitantly.

      The use of TVM has decreased due to the FDA-warnings and litigations concerning mainly the
      risks of erosion and pain. This has lead to withdrawals of mesh products, despite
      well-conducted clinical studies indicating that in well-chosen women light-weight small TVM
      is not associated with major complications. Currently, no TVM with good quality clinical data
      is available. Traditionally, CSP has been considered safer than TVM in regard of erosions and
      pain, but the data is scarce. Furthermore, CSP has a longer learning-curve and is a more
      time-consuming operation than TVM, whereas hospital stay is shorter.

      To the investigators knowledge, there is only one published study where TVM and CSP has been
      compared, and in that study a large "covering" TVM was used which was thereafter withdrawn
      from the market. In addition,in most studies, operation techniques, especially with CSP are
      not standardized. Therefore, further head-to-head comparisons are needed. The investigators
      propose a study comparing efficacy and safety when using the TVM or CSP approach in women
      with an apical defect. The investigators will also evaluate whether, in CSP, apical fixation
      alone is sufficient, or whether levator plane fixation provide a better outcome.

      Study objective:

      The main objective of the study is to compare subjective efficacy (PFDI-20, question nro 3;
      feeling of bulge) between TVM and CSP in women with an apical prolapse. The CSP group is
      further divided into two sub-groups; one where the mesh fixation is only at the apical part
      of the vagina, and another where the fixation is also extended to the levator plane.

      The secondary outcomes are safety (peri- and post-surgery complications, pain, erosion),
      objective efficacy (simplified POP-Q), and re-operation rate. Subjective outcome also
      includes the assessment of sexual satisfaction. Cost-effectiveness is studied by comparing
      both direct costs and QALYs.

      Inclusion criteria:

      Age over 18 years and capability to understand the study protocol either in Finnish or
      Swedish.

      Objectively diagnosed symptomatic apical prolapse (leading apical prolapse (points C/D ≥-2)
      and a history of previous POP operation including hysterectomy.

      No need for any other concomitant operations except colporrhaphies and possible prophylactic
      salpingo-oophorectomy in CSP groups

      Exclusion criteria:

      A history of previous serious or prolonged pain after any operation. Regular use of systemic
      corticosteroid medication. Incapability to understand the study protocol.

      Groups, procedures, and randomization:

      The participants are randomized into three groups:

        1. Transvaginal mesh: BSC mesh (A.M.I., Feldkirch, Austria) is attached to the sacrospinous
           ligaments and to the apical part of the vagina. Briefly, 0,25% Lidocain solution with
           adrenaline is injected to the anterior vaginal wall and towards the sacrospinous
           ligaments bilaterally to reduce bleeding and aid dissection. A vertical incision to the
           anterior vaginal wall is done from a point below the bladder neck to approximately 1cm
           from the vaginal apex. A full-thickness blunt dissection is done leaving the vaginal
           fascia laterally, with tunneling to the sacrospinous ligaments. The two arms of the mesh
           are attached with an i-Stich instrument (A.M.I.) to the sacrospinous ligaments 1-2 cm
           laterally from the ischial spines. The anterior edge of the mesh is attached to the
           vaginal fascia with three Monocryl 3-0 sutures. If needed, the mesh may be shortened in
           length and is so, the removed piece is measured and recorded. The arms of the mesh are
           set to the stage that the vaginal wall is reduced to its natural position. Complete
           vaginal wound closure is done with Vicryl 3-0 sutures. A roll of vaginal gauze for
           compression is applied and foley catheter inserted until the following morning. A single
           i.v. dose of 1.5g cefuroxime antibiotic is given at the time of anesthesia induction.

        2. Colposacropexy with the apical fixation only: EndoGYNious (A.M.I., Feldkirch, Austria)
           CSP mesh is attached laparoscopically to the apical part of the vagina. Briefly, a
           single i.v. dose 1.5 g of cefuroxime is administered at the time of the anesthesia
           induction. The umbilical entry is done optically by a 11 mm trocar and a
           pneumoperitoneum up to 12 mmHg is created (then lowered to 8 mmHg, if possible, after
           all trocars are inserted). A five mm trocar is placed to the left lower abdomen, a 11 mm
           trocar on the left side superior to the previous and a 7.5 mm Airseal trocar to the
           right lower abdomen. The promontory is visualized and the avascular space is dissected
           by an advanced energy instrument (Thunderbeat, Olympus). The right ureter, the major
           vessels and the right hypogastric nerve trunk are identified and avoided during the
           dissection. Opening of the right pelvic peritoneum is done with dissection of the
           pararectal space. The posterior vaginal peritoneum is opened below the level of the
           insertions of the uterosacral ligaments (USL) and the opening is extended to the
           peritoneum over the left pararectal area. The rectovaginal and the left pararectal
           spaces are dissected to create a posterior peritoneal flap. Anteriorly, the peritoneum
           below the vaginal apex is opened and dissected to create an anterior peritoneal flap. A
           CSP mesh is fixed to the vaginal apex with five non-absorbable Surgilon 2-0 sutures
           utilizing an extracorporeal knot-tying technique: three in a row to the apex and two to
           the sides two centimeters posterior to the apex (or alternatively three sutures to the
           cervix if it is present). A vaginal speculum examination is performed and any sutures
           penetrating the vaginal mucosa are removed and replaced with new ones. The tension of
           the mesh is controlled visually via a speculum examination. Anterior and/or posterior
           colporraphy is introduced at this point if a vaginal wall prolapse exceeding -2 position
           is seen after tensioning the mesh. The mesh is attached to the promontory with five
           fasteners (CapSure, Bard). The peritoneum is closed by a running V-Loc Colposacropexy
           with apical and levator fixation: EndoGYNious (A.M.I., Feldkirch, Austria) CSP mesh is
           attached via laparoscopy to the apical part of the vagina with fixation reaching to the
           level of levator plane.

        3. Colposacropexy with the apical and the levator fixation: EndoGYNious (A.M.I., Feldkirch,
           Austria) CSP mesh is attached laparoscopically to the apical part of the vagina with
           fixation reaching to the level of the levator planes. Briefly, the technique is similar
           to the apical fixation with the following exceptions: the pararectal spaces are
           dissected deep to the level of the levator ani muscles and the CSP mesh is fixed with 11
           sutures (figure) (two to the levator ani muscles, two to the insertions of the USLs and
           two to the midline of the posterior vaginal wall; the apical fixation is done similar to
           the former group).

      In all groups concomitant colporrhaphies can be conducted. Anterior or posterior colporraphy
      is done in the following fashion: a 0,25% lidocaine solution containing adrenaline is
      injected under the anterior or posterior vaginal wall to provide haemostasis and
      hydrodissection. The vaginal wall is incised and the fascia is separated from the vaginal
      epithelium using a combination of sharp and blunt dissection. The fascia is plicated using a
      running 3-0 PDS suture in two layers. Excess vaginal epithelium is excised and the vaginal
      epithelium is closed with a running 3-0 Vicryl suture.

      All the operators have conducted at least ten surgeries with the mesh before taking part into
      the study.

      Power calculation:

      The primary outcome is subjective success; defined as the absence of vaginal bulge, i.e.
      negative response to PDFI-20, question 3 at one-year following the surgery. Previous
      literature show various results. Altman et al (NEJM 2011) described that this outcome was
      achieved in 61% of women following a transvaginal mesh surgery. A prospective study by Duraes
      et al (2019) and Wei et al described an even higher success of 92% to 94%. Laparoscopic CSP
      has shown a subjective success rate of 91% to 94%. Based on these findings we assumed that
      the subjective success would be 80% following laparoscopic CSP and 75% following a TVM. The
      TVM operation is the study population that is compared to the laparoscopic CSP performed in
      two different technique (see methods).

      The statistical power is based on a non-inferiority assumption with a binary outcome. On the
      basis of previous studies we estimated that 96 patients are needed in each group for 80%
      power to detect a 20% difference in the primary outcome measure, with a two-tailed error of
      1%.

      A drop-out ratio of 10% is assumed and 106 women are needed in each group (transvaginal mesh,
      laparoscopic colposacropexy type A and laparoscopic colposarcopexy type B). Thus, a total of
      318 women are planned to be randomized for the study.

      Subjective outcome:

      Symptom spesific: Pelvic floor Distress Inventory (PFDI-20), Pelvic floor Impact
      Questionnaire (PFIQ), Pelvic Organ Prolapse / Urinary Incontinence Sexual Questionnaire
      (PISQ-12) Overall quality of life: 15D and RAND-36 questionnaires Pain is evaluated by visual
      analogue scale (VAS; 0-10) scale. The questionnaires are filled preoperatively, and after 6
      months, 12 months, and 5 years.

      Objective outcome:

      Evaluation of the leading part of the apical point, and anterior and posterior vaginal walls
      (cm in relation to the hymen level) preoperatively, and after 6 months, 12 months, and 5
      years.

      Peri- and postoperative (both short- and long-term) complications and possible re-operations
      are recorded and classified according to the Claviend-Dindo.

      Operation time, hospital stay, length of sick leave and costs of medications for operation
      and possible complications are recorded.

      Cost-effectiveness:

      Direct and indirect costs cover length of operation time, length of hospital stay, needed
      pain medication at home, other needed medication, length of sick leave, costs of possible
      further outpatient department visits or hospital stay with possible re-operations.

      QALY calculations are based on 15D and RAND-36 questionnaires.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Subjective success; defined as the absence of vaginal bulge
time frame: 5 years
description: Negative response to PDFI-20, question 3, at one-year following the surgery
measure: Peri and post-operative complications
time frame: 1 year
description: peri- and post-operative complications as recorded in medical charts
measure: Post-operative pain
time frame: 1 year
description: Pain is evaluated by visual analogue scale (VAS; 0-10) scale
measure: Objective efficacy
time frame: 1 year
description: simplified POP-Q
measure: Re-operation rate
time frame: 1 year
description: re-operations
measure: Cost-effectiveness
time frame: 1 year
description: Studied by comparing both direct costs and QALYs.
arm group label: Transvaginal mesh
arm group type: Active Comparator
description: BSC mesh (A.M.I., Feldkirch, Austria) is attached to the sacrospinosus ligaments and to the apical part of the vagina.
arm group label: Colposacropexy with the apical fixation only
arm group type: Active Comparator
description: EndoGYNious (A.M.I.) CSP mesh is attached laparoscopically to the apical part of the vagina.
arm group label: Colposacropexy with the apical and the levator fixation
arm group type: Active Comparator
description: EndoGYNious (A.M.I.) CSP mesh is attached laparoscopically to the apical part of the vagina with fixation reaching to the level of the levator planes.
intervention type: Procedure
intervention name: TVM
description: Transvaginal mesh operation using BSC mesh (A.M.I., Feldkirch, Austria)
arm group label: Transvaginal mesh
intervention type: Procedure
intervention name: Colposacropexy
description: Colposacropexy using EndoGYNious mesh (A.M.I., Feldkirch, Austria)
arm group label: Colposacropexy with the apical and the levator fixation
arm group label: Colposacropexy with the apical fixation only
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tomi Mikkola, Prof.
phone: +358504271187
email: tomi.mikkola@hus.fi
last name: Camilla Isaksson, MD
email: camilla.isaksson@hus.fi
facility: 
status: Recruiting
contact: 
country: Finland
responsible party type: Principal Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Camilla Isaksson
investigator title: Senior consultant
mesh term: Uterine Prolapse
mesh term: Prolapse
mesh term: Pelvic Organ Prolapse
sharing ipd: No