<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/NCT04433390</url>
  </required_header>
  <id_info>
    <org_study_id>2019-09</org_study_id>
    <nct_id>NCT04433390</nct_id>
  </id_info>
  <brief_title>Effect of Naloxegol on Postoperative Ileus in Patients Undergoing Cardiac Surgery</brief_title>
  <acronym>TRANSIT</acronym>
  <official_title>Time to Transit Recovery After Treatment With Naloxegol in Cardiac Surgery Intensive Care Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CMC Ambroise Paré</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CMC Ambroise Paré</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>
      Postoperative ileus, defined as the transient postoperative functional inhibition of&#xD;
      propulsive bowel activity, commonly occurs in patients after cardiac surgery and contributes&#xD;
      to postoperative morbidity.&#xD;
&#xD;
      Naloxegol is a peripheral opioid receptor antagonist. Recent studies showed that naloxegol is&#xD;
      effective in the treatment of chronic opioid-induced constipation but there is no data on its&#xD;
      use in the management of postoperative ileus after cardiac surgery.&#xD;
&#xD;
      The main objective of this prospective, double-blind, randomized, placebo-controlled trial is&#xD;
      to assess the effectiveness of the perioperative use of naloxegol in reducing the duration of&#xD;
      the postoperative ileus in patients undergoing cardiac surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Digestive complications following cardiac surgery, such as paralytic ileus and Ogilvie&#xD;
      syndrome, are frequent and worsen the prognosis of patients. They pose a real problem of care&#xD;
      in intensive care, inducing morbidity and mortality, extended hospital stay and a significant&#xD;
      post-operative cost.&#xD;
&#xD;
      Few treatments are effective to reduce transit recovery time, except the neostigmine which&#xD;
      has a serious side effects including cardiac ones.&#xD;
&#xD;
      During cardiac surgery, opioid treatments are frequently used to relieve the pain like&#xD;
      sternotomy pain.&#xD;
&#xD;
      The pharmacologic effect of opioid induces the postoperative uleus. Opioid receptors are&#xD;
      distributed in the central nervous system, where they are involved in the perception of pain,&#xD;
      and in the peripheral nervous system, especially in the mesenteric nervous system, where they&#xD;
      regulate intestinal peristalsis.&#xD;
&#xD;
      Morphine receptors antagonist are a target for prevention and treatment of post operative&#xD;
      ileus syndrome such as alvimopan and naloxone.&#xD;
&#xD;
      A therapeutic trial demonstrates a decrease in the rate of pneumonia in intensive care&#xD;
      patient mechanically ventilated who received naloxone.&#xD;
&#xD;
      Naloxegol is a peripheral antagonist of opioid receptor, from the alvimopan family. It has&#xD;
      been designed to antagonize the peripheral, but not central, effects of opioids at&#xD;
      therapeutic doses. Naloxegol is a substrate for cytochrome P450 (CYP 3A4). Following oral&#xD;
      administration, naloxegol is absorbed rapidly, with peak concentrations achieved at less than&#xD;
      2 hours.&#xD;
&#xD;
      After once daily administration, plasma concentration equilibrium is reached within 2-3 days&#xD;
      with minimal accumulation.&#xD;
&#xD;
      The main route of elimination for naloxegol is hepatic. Naloxegol has been shown to be&#xD;
      effective in randomized trials of chronic opioid induced constipation, but there is no data&#xD;
      on its use in the postoperative ileus.&#xD;
&#xD;
      Research hypothesis: the addition of naloxegol in pre and postoperative cardiac surgery could&#xD;
      reduce the time to transit recovery and the rate of digestive and respiratory complications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">March 3, 2022</completion_date>
  <primary_completion_date type="Actual">January 28, 2022</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>the nurse giving the treatment is not the outcomes assessor.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the effect of perioperative naloxegol administration on the duration of postoperative ileus after cardiac surgery</measure>
    <time_frame>5 days</time_frame>
    <description>Time (hour) to transit recovery after cardiac surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of digestive complications</measure>
    <time_frame>30 days</time_frame>
    <description>rate of digestive complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the effect of the administration of Naloxegol on respiratory complications</measure>
    <time_frame>30 days</time_frame>
    <description>rate of respiratory complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the effect of the administration of Naloxegol on infectious complications</measure>
    <time_frame>30 days</time_frame>
    <description>rate of infectious complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Verify the effectiveness of analgesia</measure>
    <time_frame>day 1, day2, day3</time_frame>
    <description>Pain Visual Analogue Scale (VAS) ranging from 0 to 10 (0=no pain, 10=worst possible pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the length of hospital stay</measure>
    <time_frame>30 days</time_frame>
    <description>Duration of hospital stay (days)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the length of ICU stay</measure>
    <time_frame>30 days</time_frame>
    <description>Duration of ICU stay (days)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">305</enrollment>
  <condition>Postoperative Ileus (Post Cardiac Surgery Constipation)</condition>
  <arm_group>
    <arm_group_label>Naloxegol group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>naloxégol tablet by oral route</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>inert tablet by oral route</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Naloxegol</intervention_name>
    <description>one naloxegol 12.5 mg tablet will be administrated 2 hours before surgery. One 25 mg naloxegol tablet per day will be administrated from 24h post-surgery until bowel movement; for maximum 5 days.</description>
    <arm_group_label>Naloxegol group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>inert tablet</intervention_name>
    <description>one inert tablet will be administrated 2 hours before surgery. One inert tablet per day will be administrated from 24h post-surgery until bowel movement; for maximum 5 days.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 18 years old,&#xD;
&#xD;
          -  Undergoing cardiac surgery with cardiopulmonary bypass,&#xD;
&#xD;
          -  For women of child bearing potential without contraception, beta-HCG negative result&#xD;
&#xD;
          -  Having signed a written informed consent form,&#xD;
&#xD;
          -  Affiliation to the social security system.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy or known hypersensitivity to Naloxegol or any of the excipients or any other&#xD;
             opioid antagonist&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Severe hepatic failure, history of cirrhosis&#xD;
&#xD;
          -  Moderate or severe renal failure (GFR&lt;60ml/min)&#xD;
&#xD;
          -  Concomitant treatment with a strong cytochrome P450 3A4 inhibitor&#xD;
&#xD;
          -  History of acute gastro-intestinal obstruction known or suspected&#xD;
&#xD;
          -  History of digestive arteritis&#xD;
&#xD;
          -  Clinically relevant alteration of the blood-brain-barrier&#xD;
&#xD;
          -  Cancer with increased risk of gastro-duodenal perforation&#xD;
&#xD;
          -  Disorder that could alter the integrity of the gastrointestinal lining&#xD;
&#xD;
          -  Regular treatment with laxative drugs&#xD;
&#xD;
          -  Concomitant treatment with methadone&#xD;
&#xD;
          -  Patient unable to take a drug by oral route&#xD;
&#xD;
          -  Patient under protection of the adults (guardianship, curators or safeguard of&#xD;
             justice),&#xD;
&#xD;
          -  Patient included or planning to be included in another research protocol relating to&#xD;
             medications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CMC Ambroise Paré</name>
      <address>
        <city>Neuilly-sur-Seine</city>
        <state>Neuilly Sur Seine</state>
        <zip>92200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>March 7, 2022</last_update_submitted>
  <last_update_submitted_qc>March 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Opioid induced constipation</keyword>
  <keyword>cardiac surgery</keyword>
  <keyword>transit recovery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ileus</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naloxegol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 6, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04433390
org study id: 2019-09
nct id: NCT04433390
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Postoperative ileus, defined as the transient postoperative functional inhibition of
      propulsive bowel activity, commonly occurs in patients after cardiac surgery and contributes
      to postoperative morbidity.

      Naloxegol is a peripheral opioid receptor antagonist. Recent studies showed that naloxegol is
      effective in the treatment of chronic opioid-induced constipation but there is no data on its
      use in the management of postoperative ileus after cardiac surgery.

      The main objective of this prospective, double-blind, randomized, placebo-controlled trial is
      to assess the effectiveness of the perioperative use of naloxegol in reducing the duration of
      the postoperative ileus in patients undergoing cardiac surgery.
Digestive complications following cardiac surgery, such as paralytic ileus and Ogilvie
      syndrome, are frequent and worsen the prognosis of patients. They pose a real problem of care
      in intensive care, inducing morbidity and mortality, extended hospital stay and a significant
      post-operative cost.

      Few treatments are effective to reduce transit recovery time, except the neostigmine which
      has a serious side effects including cardiac ones.

      During cardiac surgery, opioid treatments are frequently used to relieve the pain like
      sternotomy pain.

      The pharmacologic effect of opioid induces the postoperative uleus. Opioid receptors are
      distributed in the central nervous system, where they are involved in the perception of pain,
      and in the peripheral nervous system, especially in the mesenteric nervous system, where they
      regulate intestinal peristalsis.

      Morphine receptors antagonist are a target for prevention and treatment of post operative
      ileus syndrome such as alvimopan and naloxone.

      A therapeutic trial demonstrates a decrease in the rate of pneumonia in intensive care
      patient mechanically ventilated who received naloxone.

      Naloxegol is a peripheral antagonist of opioid receptor, from the alvimopan family. It has
      been designed to antagonize the peripheral, but not central, effects of opioids at
      therapeutic doses. Naloxegol is a substrate for cytochrome P450 (CYP 3A4). Following oral
      administration, naloxegol is absorbed rapidly, with peak concentrations achieved at less than
      2 hours.

      After once daily administration, plasma concentration equilibrium is reached within 2-3 days
      with minimal accumulation.

      The main route of elimination for naloxegol is hepatic. Naloxegol has been shown to be
      effective in randomized trials of chronic opioid induced constipation, but there is no data
      on its use in the postoperative ileus.

      Research hypothesis: the addition of naloxegol in pre and postoperative cardiac surgery could
      reduce the time to transit recovery and the rate of digestive and respiratory complications.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: the nurse giving the treatment is not the outcomes assessor.
measure: Evaluate the effect of perioperative naloxegol administration on the duration of postoperative ileus after cardiac surgery
time frame: 5 days
description: Time (hour) to transit recovery after cardiac surgery
measure: Incidence of digestive complications
time frame: 30 days
description: rate of digestive complications
measure: Evaluate the effect of the administration of Naloxegol on respiratory complications
time frame: 30 days
description: rate of respiratory complications
measure: Evaluate the effect of the administration of Naloxegol on infectious complications
time frame: 30 days
description: rate of infectious complications
measure: Verify the effectiveness of analgesia
time frame: day 1, day2, day3
description: Pain Visual Analogue Scale (VAS) ranging from 0 to 10 (0=no pain, 10=worst possible pain)
measure: Compare the length of hospital stay
time frame: 30 days
description: Duration of hospital stay (days)
measure: Compare the length of ICU stay
time frame: 30 days
description: Duration of ICU stay (days)
arm group label: Naloxegol group
arm group type: Experimental
description: naloxégol tablet by oral route
arm group label: Placebo group
arm group type: Placebo Comparator
description: inert tablet by oral route
intervention type: Drug
intervention name: Naloxegol
description: one naloxegol 12.5 mg tablet will be administrated 2 hours before surgery. One 25 mg naloxegol tablet per day will be administrated from 24h post-surgery until bowel movement; for maximum 5 days.
arm group label: Naloxegol group
intervention type: Drug
intervention name: inert tablet
description: one inert tablet will be administrated 2 hours before surgery. One inert tablet per day will be administrated from 24h post-surgery until bowel movement; for maximum 5 days.
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Ileus
mesh term: Constipation
mesh term: Naloxegol
sharing ipd: No
submitted: June 6, 2023