<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/NCT03800745</url>
  </required_header>
  <id_info>
    <org_study_id>FLA 18-069</org_study_id>
    <nct_id>NCT03800745</nct_id>
  </id_info>
  <brief_title>Reduction of Postoperative Gastrointestinal Dysmotility Following Total Laparoscopic Hysterectomy.</brief_title>
  <official_title>Reduction of Postoperative Gastrointestinal Dysmotility Following Total Laparoscopic Hysterectomy: a Randomized Control Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Michael Sprague MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pamela Frazzini-Padilla MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Katherine Smith MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jennifer Afton Cooper MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Return of bowel function is an integral component of postoperative recovery following&#xD;
      minimally invasive gynecologic surgery. To date, there is no standardized regimen to optimize&#xD;
      bowel motility postoperatively. Clinical practices vary in the medications prescribed to&#xD;
      facilitate this process, as well as what is considered the norm for return of flatus and time&#xD;
      to first bowel movement.&#xD;
&#xD;
      This study is a randomized control trial. The primary outcome of the study is to assess the&#xD;
      effect of a standardized postoperative bowel care regimen on return of bowel function by&#xD;
      assessing the time to first bowel movement; a secondary outcome is to assess the effect of&#xD;
      such a regimen on time to first flatus. The hypothesis is that the prescription of a&#xD;
      laxative, rather than a stool softener or no agent, will expedite the time to first bowel&#xD;
      movement and first flatus. Other secondary outcomes and endpoints are assessing narcotic use&#xD;
      measured in total oral morphine equivalents in the first five days postoperatively, as well&#xD;
      as the constipation score and the PAC-SYM questionnaire.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients undergoing minimally invasive hysterectomy at Cleveland Clinic Florida Department of&#xD;
      Minimally Invasive Gynecologic Surgery will be recruited at their preoperative visit or over&#xD;
      the phone. Inclusion criteria will be patients aged 18-85 undergoing minimally invasive&#xD;
      gynecologic surgery in the form of total laparoscopic hysterectomy. Exclusion criteria are an&#xD;
      underlying gynecologic malignancy, pre-existing gastrointestinal disorders, history of bowel&#xD;
      resection, insulin-dependent diabetes or gastroparesis, known gastric dysmotility, chronic&#xD;
      use of pain medications, or anticipated bowel surgery. Subjects that routinely take laxatives&#xD;
      will be included in a sub-analysis. Randomization will occur in the immediate postoperative&#xD;
      period. Enrolled subjects will be randomized using a computer generator. A total sample size&#xD;
      of 72 subjects, with 24 subjects in each arm, is needed to attain a significance level of 95%&#xD;
      at a power of 80% to demonstrate a reduction of 24 hours or more to first postoperative bowel&#xD;
      movement. Accounting for a 10% attrition rate, we will aim to recruit 81 patients total with&#xD;
      27 subjects in each arm. The control group, arm A, will be not be prescribed any&#xD;
      postoperative bowel care regimen. The first study group, arm B, will be prescribed docusate&#xD;
      sodium(Colace) 100mg twice daily orally, and will be instructed to begin taking this the&#xD;
      evening of surgery through postoperative day five. One dose will be taken with breakfast&#xD;
      every morning, and the second dose will be taken with dinner every evening. The second study&#xD;
      group, arm C, will be prescribed Miralax 17 grams oral powder pack daily with breakfast, and&#xD;
      will be instructed to begin taking this the morning after surgery through postoperative day&#xD;
      five. Prescriptions will be given at the time of randomization immediately postoperatively&#xD;
      and prior to discharge home. At Cleveland Clinic Florida, a majority of patients are&#xD;
      discharged the day of surgery.&#xD;
&#xD;
      In addition, the presence of preoperative constipation will be assessed prior to surgery&#xD;
      based on the Rome IV criteria along with baseline stool consistency as per the Bristol Stool&#xD;
      Chart. Postoperatively, patients will be asked to record the time of first flatus and time&#xD;
      first bowel movement. Each subject will complete the Patient Assessment of Constipation&#xD;
      Symptoms (PAC-SYM) validated questionnaire on postoperative day 5, and a constipation score&#xD;
      will also be calculated. Compliance with postoperative medications will also be assessed as&#xD;
      defined by the number of medications taken as prescribed. Patients will record medications&#xD;
      taken each day in a medication diary.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 9, 2018</start_date>
  <completion_date type="Actual">May 5, 2020</completion_date>
  <primary_completion_date type="Actual">May 5, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>randomized control trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Participants are randomized to their arm on the day of surgery. A manila envelope with the arm written on a paper inside the envelope is opened in the post-anesthesia care unit (PACU) following surgery. A computerized random number generator was used to assign arms.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time to First Bowel Movement</measure>
    <time_frame>Patients will be followed for the first 5 days after surgery.</time_frame>
    <description>The primary outcome of the study is to assess the effect of a standardized postoperative bowel care regimen on return of bowel function by assessing the date and time of first BM after surgery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to First Flatus</measure>
    <time_frame>Patients will be followed for the first 5 days after surgery.</time_frame>
    <description>Secondary outcomes include the time to first flatus. This will be calculated as the difference between the date and end time of the subject's surgery and the date and time of first BM after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Narcotic Use</measure>
    <time_frame>Patients will be followed for the first 5 days after surgery.</time_frame>
    <description>Postoperative narcotic use in oral morphine equivalents in the first five days postoperatively will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PAC-SYM Questionnaire</measure>
    <time_frame>Patients will be followed for the first 5 days after surgery.</time_frame>
    <description>To assess for opioid-induced constipation. Postoperatively, the Patient Assessment of Constipation-Symptom Questionnaire will be administered on postoperative day 5 to assess 12 different symptoms regarding bowel function.The 12-item questionnaire is divided into three symptom subscales: abdominal (four items); rectal (three items); and stool (five items). Items are scored on 5-point Likert scales, with scores ranging from 0 to 4 (0 = 'symptom absent', 1 = 'mild', 2 = 'moderate', 3 = 'severe' and 4 = 'very severe'). A mean total score in the range of 0-4 is generated by dividing the total score by the number of questions completed; the lower the total score, the lower the symptom burden. Historically, a reduction in total score of 1 point or more has been used as the cut-off to define a positive response to treatment, 2 implying that this is a meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Constipation Score</measure>
    <time_frame>The first 5 days after surgery.</time_frame>
    <description>A postoperative constipation score is calculated based on preoperative stool frequency, postoperative days to first BM, stool consistency, percentage of straining, and sensation of incomplete evacuation. Constipation scores are calculated basedon: days to first BM (2 points if &gt;4 days, 0 points if 1-3 days); stool consistency (1 point if types 1 or 2, 0 points for types 3-7); strain rating (0.5 points if for ≥5 on ≥25% of the BMs; 0 points for ≤4 on 0-25%); 0.5 point for rating of mild, moderate, or severe for sense of incomplete evacuation to the question: &quot;Have you experienced incomplete bowel movement, like you did not finish?&quot; with 0 point for rating of none). The Straining Scale is a single-item questionnaire assessing straining on a 5 point Likert scale ranging from 1 to 5 in the following order: no straining, mild, moderate, severe, or very severe straining. A constipation score of 2 or more is consistent with constipation based on the Rome III criteria.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Postoperative Passage of Flatus</condition>
  <condition>Postoperative Bowel Movement</condition>
  <arm_group>
    <arm_group_label>No Medication</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention is assigned in Arm A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Colace</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is Arm B. Docusate sodium(Colace) is prescribed as100mg twice daily orally. Patients will be instructed to begin taking this the evening of surgery through postoperative day five.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Miralax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is Arm C. Miralax 17 grams oral powder pack daily is prescribed to be taken with breakfast. Patients will be instructed to begin taking this the morning after surgery through postoperative day five.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colace 100Mg Capsule</intervention_name>
    <description>Prescribed to Arm B</description>
    <arm_group_label>Colace</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Miralax</intervention_name>
    <description>Prescribed to Arm C</description>
    <arm_group_label>Miralax</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged 18-85 undergoing minimally invasive gynecologic surgery in the form of total&#xD;
             laparoscopic hysterectomy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  an underlying gynecologic malignancy, pre-existing gastrointestinal disorders, history&#xD;
             of bowel resection, insulin-dependent diabetes or gastroparesis, known gastric&#xD;
             dysmotility, chronic use of pain medications, or anticipated bowel surgery&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cleveland Clinic Florida</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Mehandru, Natasha</investigator_full_name>
    <investigator_title>Sub-Investigator; Study Coordinator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polyethylene glycol 3350</mesh_term>
  </intervention_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/NCT03800745
org study id: FLA 18-069
nct id: NCT03800745
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Return of bowel function is an integral component of postoperative recovery following
      minimally invasive gynecologic surgery. To date, there is no standardized regimen to optimize
      bowel motility postoperatively. Clinical practices vary in the medications prescribed to
      facilitate this process, as well as what is considered the norm for return of flatus and time
      to first bowel movement.

      This study is a randomized control trial. The primary outcome of the study is to assess the
      effect of a standardized postoperative bowel care regimen on return of bowel function by
      assessing the time to first bowel movement; a secondary outcome is to assess the effect of
      such a regimen on time to first flatus. The hypothesis is that the prescription of a
      laxative, rather than a stool softener or no agent, will expedite the time to first bowel
      movement and first flatus. Other secondary outcomes and endpoints are assessing narcotic use
      measured in total oral morphine equivalents in the first five days postoperatively, as well
      as the constipation score and the PAC-SYM questionnaire.
Patients undergoing minimally invasive hysterectomy at Cleveland Clinic Florida Department of
      Minimally Invasive Gynecologic Surgery will be recruited at their preoperative visit or over
      the phone. Inclusion criteria will be patients aged 18-85 undergoing minimally invasive
      gynecologic surgery in the form of total laparoscopic hysterectomy. Exclusion criteria are an
      underlying gynecologic malignancy, pre-existing gastrointestinal disorders, history of bowel
      resection, insulin-dependent diabetes or gastroparesis, known gastric dysmotility, chronic
      use of pain medications, or anticipated bowel surgery. Subjects that routinely take laxatives
      will be included in a sub-analysis. Randomization will occur in the immediate postoperative
      period. Enrolled subjects will be randomized using a computer generator. A total sample size
      of 72 subjects, with 24 subjects in each arm, is needed to attain a significance level of 95%
      at a power of 80% to demonstrate a reduction of 24 hours or more to first postoperative bowel
      movement. Accounting for a 10% attrition rate, we will aim to recruit 81 patients total with
      27 subjects in each arm. The control group, arm A, will be not be prescribed any
      postoperative bowel care regimen. The first study group, arm B, will be prescribed docusate
      sodium(Colace) 100mg twice daily orally, and will be instructed to begin taking this the
      evening of surgery through postoperative day five. One dose will be taken with breakfast
      every morning, and the second dose will be taken with dinner every evening. The second study
      group, arm C, will be prescribed Miralax 17 grams oral powder pack daily with breakfast, and
      will be instructed to begin taking this the morning after surgery through postoperative day
      five. Prescriptions will be given at the time of randomization immediately postoperatively
      and prior to discharge home. At Cleveland Clinic Florida, a majority of patients are
      discharged the day of surgery.

      In addition, the presence of preoperative constipation will be assessed prior to surgery
      based on the Rome IV criteria along with baseline stool consistency as per the Bristol Stool
      Chart. Postoperatively, patients will be asked to record the time of first flatus and time
      first bowel movement. Each subject will complete the Patient Assessment of Constipation
      Symptoms (PAC-SYM) validated questionnaire on postoperative day 5, and a constipation score
      will also be calculated. Compliance with postoperative medications will also be assessed as
      defined by the number of medications taken as prescribed. Patients will record medications
      taken each day in a medication diary.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: randomized control trial
primary purpose: Prevention
masking: None (Open Label)
masking description: Participants are randomized to their arm on the day of surgery. A manila envelope with the arm written on a paper inside the envelope is opened in the post-anesthesia care unit (PACU) following surgery. A computerized random number generator was used to assign arms.
measure: Time to First Bowel Movement
time frame: Patients will be followed for the first 5 days after surgery.
description: The primary outcome of the study is to assess the effect of a standardized postoperative bowel care regimen on return of bowel function by assessing the date and time of first BM after surgery.
measure: Time to First Flatus
time frame: Patients will be followed for the first 5 days after surgery.
description: Secondary outcomes include the time to first flatus. This will be calculated as the difference between the date and end time of the subject's surgery and the date and time of first BM after surgery.
measure: Narcotic Use
time frame: Patients will be followed for the first 5 days after surgery.
description: Postoperative narcotic use in oral morphine equivalents in the first five days postoperatively will be measured.
measure: PAC-SYM Questionnaire
time frame: Patients will be followed for the first 5 days after surgery.
description: To assess for opioid-induced constipation. Postoperatively, the Patient Assessment of Constipation-Symptom Questionnaire will be administered on postoperative day 5 to assess 12 different symptoms regarding bowel function.The 12-item questionnaire is divided into three symptom subscales: abdominal (four items); rectal (three items); and stool (five items). Items are scored on 5-point Likert scales, with scores ranging from 0 to 4 (0 = 'symptom absent', 1 = 'mild', 2 = 'moderate', 3 = 'severe' and 4 = 'very severe'). A mean total score in the range of 0-4 is generated by dividing the total score by the number of questions completed; the lower the total score, the lower the symptom burden. Historically, a reduction in total score of 1 point or more has been used as the cut-off to define a positive response to treatment, 2 implying that this is a meaningful improvement.
measure: Constipation Score
time frame: The first 5 days after surgery.
description: A postoperative constipation score is calculated based on preoperative stool frequency, postoperative days to first BM, stool consistency, percentage of straining, and sensation of incomplete evacuation. Constipation scores are calculated basedon: days to first BM (2 points if >4 days, 0 points if 1-3 days); stool consistency (1 point if types 1 or 2, 0 points for types 3-7); strain rating (0.5 points if for ≥5 on ≥25% of the BMs; 0 points for ≤4 on 0-25%); 0.5 point for rating of mild, moderate, or severe for sense of incomplete evacuation to the question: "Have you experienced incomplete bowel movement, like you did not finish?" with 0 point for rating of none). The Straining Scale is a single-item questionnaire assessing straining on a 5 point Likert scale ranging from 1 to 5 in the following order: no straining, mild, moderate, severe, or very severe straining. A constipation score of 2 or more is consistent with constipation based on the Rome III criteria.
arm group label: No Medication
arm group type: No Intervention
description: No intervention is assigned in Arm A.
arm group label: Colace
arm group type: Experimental
description: This is Arm B. Docusate sodium(Colace) is prescribed as100mg twice daily orally. Patients will be instructed to begin taking this the evening of surgery through postoperative day five.
arm group label: Miralax
arm group type: Experimental
description: This is Arm C. Miralax 17 grams oral powder pack daily is prescribed to be taken with breakfast. Patients will be instructed to begin taking this the morning after surgery through postoperative day five.
intervention type: Drug
intervention name: Colace 100Mg Capsule
description: Prescribed to Arm B
arm group label: Colace
intervention type: Drug
intervention name: Miralax
description: Prescribed to Arm C
arm group label: Miralax
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Mehandru, Natasha
investigator title: Sub-Investigator; Study Coordinator
mesh term: Polyethylene glycol 3350
sharing ipd: No