<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/NCT03826459</url>
  </required_header>
  <id_info>
    <org_study_id>PICS</org_study_id>
    <nct_id>NCT03826459</nct_id>
  </id_info>
  <brief_title>Preventing Isthmocele After Cesarean Section</brief_title>
  <acronym>(PICS)</acronym>
  <official_title>The PICS Trial: A Pilot Randomized Controlled Trial of Non-Locked vs. Locked Uterine Closure at Cesarean Section for Prevention of Uterine Isthmocele Formation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mount Sinai Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mount Sinai Hospital, Canada</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>
      Cesarean section accounts for nearly 30% of births in Canada, and is the most commonly&#xD;
      performed surgery by Obstetrician Gynecologists. Cesarean scar isthmocele, meaning a defect&#xD;
      in the uterine wall at the site of a previous uterine incision, is a common complication of&#xD;
      this surgery. While most are likely asymptomatic, isthmoceles can lead to major complications&#xD;
      in pregnancy (uterine rupture, invasive placentation, cesarean scar ectopic pregnancy) and&#xD;
      outside of pregnancy (abnormal uterine bleeding, infertility and pain). Studies have shown&#xD;
      that the method used to suture the uterus at the time of a cesarean section may have an&#xD;
      impact on the incidence of post-operative isthmocele formation. Our study is a randomized&#xD;
      control trial of the impact of locked vs unlocked uterine closure at cesarean section on the&#xD;
      incidence of isthmocele formation. Women undergoing cesarean section will be randomized to&#xD;
      have either a locked or unlocked uterine closure. They will then return 6 months after their&#xD;
      surgery for a transvaginal ultrasound to evaluate the presence or absence of an isthmocele.&#xD;
&#xD;
      This study is a pilot trial. The investigators hope to determine the feasibility of&#xD;
      completing a large randomized control trial by recording: a) the number of patient who agree&#xD;
      to participate in this study, b) the number of patients who receive the correct intervention&#xD;
      and, c) the number of patients who return for their post operative ultrasound.&#xD;
&#xD;
      The investigators also plan to assess multiple secondary outcomes. First, the goal is to&#xD;
      determine the isthmocele incidence within the study subjects of the pilot trial in order to&#xD;
      perform a power calculation for a subsequent larger trial in this area. Another goal is to&#xD;
      determine if the uterine closure techniques in this study lead to differences in surgical&#xD;
      time, blood loss or the need for intra- or post-operative blood transfusion. Last, the study&#xD;
      will collect data on the suture material most commonly used in this study to determine if&#xD;
      this requires standardization in the subsequent larger trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cesarean section accounts for nearly 30% of all deliveries in Canada, and is the most&#xD;
      commonly performed surgery by Obstetrician Gynecologists (OBGYNs) in Canada. Therefore, it is&#xD;
      important to understand the short and long-term complications of this procedure. Recently,&#xD;
      emphasis has been placed on cesarean scar isthmocele as a long-term complication. An&#xD;
      isthmocele is a defect at the cesarean section scar site with a depth of at least 1-2mm.&#xD;
      Isthmoceles can lead to major obstetrical complications such as cesarean scar pregnancy,&#xD;
      invasive placentation, and uterine rupture. More commonly, patients present with gynecologic&#xD;
      symptoms: abnormal uterine bleeding, pain, and infertility. Up to 30-50% of patients with an&#xD;
      isthmocele report symptoms when inquired. Isthmoceles have an incidence of 19-88% following&#xD;
      cesarean section. This wide range is due to discrepancies in study technique, diagnostic&#xD;
      criteria, and patient characteristics.&#xD;
&#xD;
      While medical and surgical treatment options are available for cesarean scar isthmocele, our&#xD;
      focus should turn to prevention at the time of cesarean section. Evidence suggests&#xD;
      double-layer (vs. single-layer) uterine closure decreases the formation of cesarean scar&#xD;
      isthmocele and increases residual myometrial thickness (RMT). Additionally, uterine closure&#xD;
      with a locked suturing technique may result in greater isthmocele depth and size, and a&#xD;
      thinner RMT at the cesarean scar site. To our knowledge however, no study has determined the&#xD;
      impact of a locked vs. unlocked double-layer closure technique on isthmocele prevention.&#xD;
      Locked sutures, believed to be more hemostatic, may cause tissue necrosis and impair wound&#xD;
      healing. Interestingly, evidence does not support reductions in operative blood loss with&#xD;
      locked closure techniques. The hypothesis is that unlocked double-layer uterine closure can&#xD;
      reduce isthmocele formation and thus improve longterm maternal outcomes without impacting&#xD;
      operative blood loss or other short-term surgical outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 5, 2019</start_date>
  <completion_date type="Actual">December 18, 2020</completion_date>
  <primary_completion_date type="Actual">December 18, 2020</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>
    <intervention_model_description>Participants will be randomized to either locked or non-locked uterine closure at the time of cesarean section.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Enrolled</measure>
    <time_frame>6 months</time_frame>
    <description>Number of potential participants approached who actually enrolled in the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants that Cross-Over</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants who cross-over to the other study arm (i.e. who receive the incorrect uterine closure technique)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Lost to Follow Up</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants enrolled in the trial who do not present for their follow up ultrasound at 6 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Isthmocele</measure>
    <time_frame>6 months</time_frame>
    <description>The presence of an isthmocele (minimum 2 mm x 2 mm) identified on a transvaginal ultrasound 6 months after the cesarean section</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimated Blood Loss</measure>
    <time_frame>Through surgery completion (estimated 1 hour)</time_frame>
    <description>Number of mL of blood lost at the time of cesarean section</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hemoglobin</measure>
    <time_frame>24 hours</time_frame>
    <description>Change in Hgb from pre-operative measurement to Hgb measurement on post-operative day #1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Operative Time</measure>
    <time_frame>Through surgery completion (estimated 1 hour)</time_frame>
    <description>Length of surgery (minutes)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Blood Transfusions</measure>
    <time_frame>Throughout hospital stay (estimated 48 hours)</time_frame>
    <description>Number of intraoperative and post-operative blood transfusions given to each participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional Hemostatic Sutures</measure>
    <time_frame>Start to end of surgery</time_frame>
    <description>Number of additional hemostatic sutures placed in the uterus for each participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Suture Material</measure>
    <time_frame>6 months</time_frame>
    <description>Type of suture material used for hysterotomy closure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Additional Oxytocin in Units</measure>
    <time_frame>Throughout hospital stay (estimated 48 hours)</time_frame>
    <description>Number of units of additional oxytocin given to each participant as a uterotonic agent (beyond usual dose of intraoperative oxytocin)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Ergotamine in mg</measure>
    <time_frame>Throughout hospital stay (estimated 48 hours)</time_frame>
    <description>Number of mg Ergotamine used as a uterotonic agent, if required</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Hemabate in mg</measure>
    <time_frame>Throughout hospital stay (estimated 48 hours)</time_frame>
    <description>Number of mg Ergotamine used as a uterotonic agent, if required</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Misoprostol in mcg</measure>
    <time_frame>Throughout hospital stay (estimated 48 hours)</time_frame>
    <description>Number of mcg Misoprostol used as a uterotonic agent, if required</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Cesarean Section Complications</condition>
  <condition>Uterine Scar Diverticulum</condition>
  <condition>Uterine Scar From Previous Cesarean Delivery</condition>
  <arm_group>
    <arm_group_label>Locked Uterine Closure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will undergo two-layer closure of the hysterotomy site at the time of cesarean section. The first layer will use a running &amp; locking technique. The second layer will be performed based on surgeon preference.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Locking Uterine Closure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will undergo two-layer closure of the hysterotomy site at the time of cesarean section. The first layer will use a running &amp; non-locking technique. The second layer will be performed based on surgeon preference, but cannot be of a locking technique.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non-Locking Uterine Closure</intervention_name>
    <description>The first layer of the two-layer uterine closure will be sutured with a running &amp; non-locking technique. The second layer cannot be of a locking technique.</description>
    <arm_group_label>Non-Locking Uterine Closure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Locked Uterine Closure</intervention_name>
    <description>The first layer of the two-layer uterine closure will be sutured with a running &amp; locking technique. The second layer can be locking or non-locking.</description>
    <arm_group_label>Locked Uterine Closure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women undergoing their first cesarean section&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous uterine hysterotomy (caesarean section, myomectomy, etc.)&#xD;
&#xD;
          -  known uterine anomalies&#xD;
&#xD;
          -  active labour&#xD;
&#xD;
          -  known bleeding disorder&#xD;
&#xD;
          -  maternal connective tissue disorders&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Since this is a study done at the time of cesarean section, only females are eligible.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mara Sobel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MOUNT SINAI HOSPITAL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 22, 2022</last_update_submitted>
  <last_update_submitted_qc>January 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mount Sinai Hospital, Canada</investigator_affiliation>
    <investigator_full_name>Mara Sobel</investigator_full_name>
    <investigator_title>Obstetrician/Gynecologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diverticulum</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/NCT03826459
org study id: PICS
nct id: NCT03826459
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cesarean section accounts for nearly 30% of births in Canada, and is the most commonly
      performed surgery by Obstetrician Gynecologists. Cesarean scar isthmocele, meaning a defect
      in the uterine wall at the site of a previous uterine incision, is a common complication of
      this surgery. While most are likely asymptomatic, isthmoceles can lead to major complications
      in pregnancy (uterine rupture, invasive placentation, cesarean scar ectopic pregnancy) and
      outside of pregnancy (abnormal uterine bleeding, infertility and pain). Studies have shown
      that the method used to suture the uterus at the time of a cesarean section may have an
      impact on the incidence of post-operative isthmocele formation. Our study is a randomized
      control trial of the impact of locked vs unlocked uterine closure at cesarean section on the
      incidence of isthmocele formation. Women undergoing cesarean section will be randomized to
      have either a locked or unlocked uterine closure. They will then return 6 months after their
      surgery for a transvaginal ultrasound to evaluate the presence or absence of an isthmocele.

      This study is a pilot trial. The investigators hope to determine the feasibility of
      completing a large randomized control trial by recording: a) the number of patient who agree
      to participate in this study, b) the number of patients who receive the correct intervention
      and, c) the number of patients who return for their post operative ultrasound.

      The investigators also plan to assess multiple secondary outcomes. First, the goal is to
      determine the isthmocele incidence within the study subjects of the pilot trial in order to
      perform a power calculation for a subsequent larger trial in this area. Another goal is to
      determine if the uterine closure techniques in this study lead to differences in surgical
      time, blood loss or the need for intra- or post-operative blood transfusion. Last, the study
      will collect data on the suture material most commonly used in this study to determine if
      this requires standardization in the subsequent larger trial.
Cesarean section accounts for nearly 30% of all deliveries in Canada, and is the most
      commonly performed surgery by Obstetrician Gynecologists (OBGYNs) in Canada. Therefore, it is
      important to understand the short and long-term complications of this procedure. Recently,
      emphasis has been placed on cesarean scar isthmocele as a long-term complication. An
      isthmocele is a defect at the cesarean section scar site with a depth of at least 1-2mm.
      Isthmoceles can lead to major obstetrical complications such as cesarean scar pregnancy,
      invasive placentation, and uterine rupture. More commonly, patients present with gynecologic
      symptoms: abnormal uterine bleeding, pain, and infertility. Up to 30-50% of patients with an
      isthmocele report symptoms when inquired. Isthmoceles have an incidence of 19-88% following
      cesarean section. This wide range is due to discrepancies in study technique, diagnostic
      criteria, and patient characteristics.

      While medical and surgical treatment options are available for cesarean scar isthmocele, our
      focus should turn to prevention at the time of cesarean section. Evidence suggests
      double-layer (vs. single-layer) uterine closure decreases the formation of cesarean scar
      isthmocele and increases residual myometrial thickness (RMT). Additionally, uterine closure
      with a locked suturing technique may result in greater isthmocele depth and size, and a
      thinner RMT at the cesarean scar site. To our knowledge however, no study has determined the
      impact of a locked vs. unlocked double-layer closure technique on isthmocele prevention.
      Locked sutures, believed to be more hemostatic, may cause tissue necrosis and impair wound
      healing. Interestingly, evidence does not support reductions in operative blood loss with
      locked closure techniques. The hypothesis is that unlocked double-layer uterine closure can
      reduce isthmocele formation and thus improve longterm maternal outcomes without impacting
      operative blood loss or other short-term surgical outcomes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomized to either locked or non-locked uterine closure at the time of cesarean section.
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Number of Participants Enrolled
time frame: 6 months
description: Number of potential participants approached who actually enrolled in the trial
measure: Number of Participants that Cross-Over
time frame: 6 months
description: Number of participants who cross-over to the other study arm (i.e. who receive the incorrect uterine closure technique)
measure: Number of Participants Lost to Follow Up
time frame: 6 months
description: Number of participants enrolled in the trial who do not present for their follow up ultrasound at 6 months.
measure: Incidence of Isthmocele
time frame: 6 months
description: The presence of an isthmocele (minimum 2 mm x 2 mm) identified on a transvaginal ultrasound 6 months after the cesarean section
measure: Estimated Blood Loss
time frame: Through surgery completion (estimated 1 hour)
description: Number of mL of blood lost at the time of cesarean section
measure: Change in Hemoglobin
time frame: 24 hours
description: Change in Hgb from pre-operative measurement to Hgb measurement on post-operative day #1
measure: Operative Time
time frame: Through surgery completion (estimated 1 hour)
description: Length of surgery (minutes)
measure: Number of Blood Transfusions
time frame: Throughout hospital stay (estimated 48 hours)
description: Number of intraoperative and post-operative blood transfusions given to each participant
measure: Additional Hemostatic Sutures
time frame: Start to end of surgery
description: Number of additional hemostatic sutures placed in the uterus for each participant
measure: Suture Material
time frame: 6 months
description: Type of suture material used for hysterotomy closure
measure: Use of Additional Oxytocin in Units
time frame: Throughout hospital stay (estimated 48 hours)
description: Number of units of additional oxytocin given to each participant as a uterotonic agent (beyond usual dose of intraoperative oxytocin)
measure: Use of Ergotamine in mg
time frame: Throughout hospital stay (estimated 48 hours)
description: Number of mg Ergotamine used as a uterotonic agent, if required
measure: Use of Hemabate in mg
time frame: Throughout hospital stay (estimated 48 hours)
description: Number of mg Ergotamine used as a uterotonic agent, if required
measure: Use of Misoprostol in mcg
time frame: Throughout hospital stay (estimated 48 hours)
description: Number of mcg Misoprostol used as a uterotonic agent, if required
arm group label: Locked Uterine Closure
arm group type: Active Comparator
description: Participants will undergo two-layer closure of the hysterotomy site at the time of cesarean section. The first layer will use a running & locking technique. The second layer will be performed based on surgeon preference.
arm group label: Non-Locking Uterine Closure
arm group type: Experimental
description: Participants will undergo two-layer closure of the hysterotomy site at the time of cesarean section. The first layer will use a running & non-locking technique. The second layer will be performed based on surgeon preference, but cannot be of a locking technique.
intervention type: Procedure
intervention name: Non-Locking Uterine Closure
description: The first layer of the two-layer uterine closure will be sutured with a running & non-locking technique. The second layer cannot be of a locking technique.
arm group label: Non-Locking Uterine Closure
intervention type: Procedure
intervention name: Locked Uterine Closure
description: The first layer of the two-layer uterine closure will be sutured with a running & locking technique. The second layer can be locking or non-locking.
arm group label: Locked Uterine Closure
criteria: 
gender: Female
gender based: Yes
gender description: Since this is a study done at the time of cesarean section, only females are eligible.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Mara Sobel, MD
role: Principal Investigator
affiliation: MOUNT SINAI HOSPITAL
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Mount Sinai Hospital, Canada
investigator full name: Mara Sobel
investigator title: Obstetrician/Gynecologist
mesh term: Diverticulum
sharing ipd: No