<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/NCT02977286</url>
  </required_header>
  <id_info>
    <org_study_id>11200</org_study_id>
    <nct_id>NCT02977286</nct_id>
  </id_info>
  <brief_title>Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids</brief_title>
  <official_title>Impact of Naloxegol on Prevention of Lower GI Tract Paralysis in Critically Ill Adults Initiated on Scheduled Intravenous Opioid Therapy: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Single-Center, Proof of Concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tufts Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tufts Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in&#xD;
      critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the&#xD;
      participants will receive naloxegol and a laxative protocol and half the participants will&#xD;
      receive a placebo and a laxative protocol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Among the more than 5 million adults who are admitted to the ICU each year in the USA, most&#xD;
      have pain and thus receive a pain (analgesic) medication called an opioid. Opioid use in&#xD;
      critically ill adults continues to increase given the greater awareness of untreated pain in&#xD;
      the ICU and that an opioid-first approach be used to optimize patient safety and comfort and&#xD;
      improve tolerance with breathing machines (i.e. mechanical ventilation). Similar to&#xD;
      constipation, paralysis of the lower gastrointestinal (GI) tract is defined as the inability&#xD;
      to pass stool due to impaired gut movement, and is a common effect of opioid use in the&#xD;
      critically ill. Lower GI tract paralysis may lead to nausea, vomiting, aspiration, compromise&#xD;
      the ability to administer tube feeds (enteral nutrition), an increase abdominal pain,&#xD;
      delirium and delay getting off mechanical ventilation. One recent randomized study found that&#xD;
      aggressive use of laxatives to prevent lower GI tract paralysis in critically ill adults was&#xD;
      associated with lower daily organ dysfunction [as measured by the Sequential Organ Failure&#xD;
      Assessment (SOFA) score]. The lower GI tract paralysis that occurs in the critically ill&#xD;
      often responds poorly to laxative medication therapy (e.g., senna, bisacodyl, lactulose).&#xD;
      While stool softener medications like docusate are routinely administered to patients on&#xD;
      opioids, laxative-based protocols are frequently not initiated in the ICU until signs of&#xD;
      lower GI tract paralysis start to appear. There is therefore an important and unmet need for&#xD;
      a safe and efficacious medication to prevent lower GI tract paralysis in critically ill&#xD;
      adults who are initiated on opioid therapy. Naloxegol (Movantik) is a naloxone-like drug that&#xD;
      blocks the effect of opioids on the opioid µ receptor in the gut but is not absorbed in the&#xD;
      brain (and therefore does not block the pain effects of opioids). Naloxegol is currently&#xD;
      approved by the Food and Drug Administration (FDA) for the treatment of opioid-induced&#xD;
      constipation (OIC) in non-ICU patients receiving scheduled moderate to high dose opioids for&#xD;
      the treatment of chronic non-cancer pain. Naloxegol has a mechanism of action, efficacy,&#xD;
      convenience of administration, and safety profile that make it an ideal candidate for use as&#xD;
      a preventative medication for lower GI tract paralysis in critically ill adults receiving&#xD;
      scheduled opioid therapy. The investigators propose a pilot study in which they will test the&#xD;
      hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous&#xD;
      bowel movement (SBM) that an ICU patient has, that it will prevent lower GI tract paralysis&#xD;
      in critically ill adults initiated on scheduled IV opioid therapy, and its use will not&#xD;
      result in side effects that are concerning to doctors or patients. The investigators will&#xD;
      randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol [25mg or&#xD;
      12.5mg (in patients with a creatinine clearance ≤ 60ml/min)] or placebo. This pilot study&#xD;
      will provide valuable information to help guide future, larger studies evaluating the role of&#xD;
      naloxegol in critically ill adults.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">October 9, 2019</completion_date>
  <primary_completion_date type="Actual">October 9, 2019</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to First Spontaneous Bowel Movement (SBM) Administration</measure>
    <time_frame>First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days</time_frame>
    <description>Time to first spontaneous bowel movement during ICU admission after randomization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to First Spontaneous Bowel Movement (SBM)</measure>
    <time_frame>First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days</time_frame>
    <description>Time to first spontaneous bowel movement during the ICU admission after opioid initiation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU Days Without a SBM</measure>
    <time_frame>During period of ICU admission or a maximum of 10 ICU days</time_frame>
    <description>Measured ICU days that subjects did not have a SBM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Loose and Unformed or Liquid SBM</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Consistency of SBM is characterized in one of 4 categories: hard and formed, soft but formed, loose and unformed, and liquid. The number listed in the results section is the number of patients who had either loose or liquid SBM (as opposed to hard or soft formed).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients That Required Use of the Study Laxative Protocol</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>A 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Daily Goal Reached for Enteral Nutrition Administration</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Fluid Balance</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Daily fluid balance measured in mL is the 24 hours ins and outs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Maximal Pain Scale Score</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Based on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment.&#xD;
VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Maximal Sedation Assessment Scale (SAS) Score</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>The Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present.&#xD;
Results listed here is days without coma (SAS score of 3-7)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation</measure>
    <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days Without Mechanical Ventilation Support for Duration of ICU Stay</measure>
    <time_frame>From ICU admission to ICU discharge or a maximum of 10 ICU days</time_frame>
    <description>Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal Pressure Measurement</measure>
    <time_frame>From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days</time_frame>
    <description>On days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Episode of Diarrhea</measure>
    <time_frame>Study drug initiation to first episode of diarrhea in hours.</time_frame>
    <description>The number of patients in each group with &gt; or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score</measure>
    <time_frame>One hour before the daily study drug administration and 2 hours after the daily study drug administration</time_frame>
    <description>Patients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Constipation</condition>
  <arm_group>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Naloxegol Oral Tablet</intervention_name>
    <description>Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <other_name>Movantik</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Placebo Oral Tablet po (enteral) twice daily</description>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Official AstraZeneca placebo for Movantik</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docusate Sodium 100 Mg oral capsule [Colace]</intervention_name>
    <description>Docusate Sodium 100 mg po (enteral) twice daily</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Colace</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Senna 217 Mg Oral Tablet</intervention_name>
    <description>Senna 127 mg oral tablet daily if no spontaneous bowel movement &gt;/=3 days after scheduled opioid initiation; increase to two senna 127 mg tables if no no spontaneous bowel movement &gt;/=4 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement &gt;/=5 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement &gt;/=6 days after scheduled opioid initiation.</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Senokot</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Polyethylene Glycols</intervention_name>
    <description>Polyethylene Glycols 17 g daily if no spontaneous bowel movement &gt;/=3 days after scheduled opioid initiation; increase to 34 g daily if no spontaneous bowel movement &gt;/=4 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement &gt;/= 5 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement &gt;/= 6 days after scheduled opioid initiation.</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Miralax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisacodyl 10 mg Suppository</intervention_name>
    <description>Insert one suppository if no spontaneous bowel movement &gt;/=4 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement &gt;/= 5 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement &gt;/= 6 days after scheduled opioid initiation.</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Dulcolax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Magnesium Citrate Oral Liquid Product</intervention_name>
    <description>Administer one 10 oz bottle if no spontaneous bowel movement &gt;/= 5 days after scheduled opioid initiation.</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Citromag</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylnaltrexone</intervention_name>
    <description>Administer 8 mg or 16 mg (depending on subject's weight) subcutaneously x 1 if no spontaneous bowel movement &gt;/= 6 days after scheduled opioid initiation, consult surgery/gastroenterology and discontinue study medication.</description>
    <arm_group_label>Naloxegol Oral Tablet</arm_group_label>
    <arm_group_label>Placebo Oral Tablet</arm_group_label>
    <other_name>Relistor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Admitted to an ICU&#xD;
&#xD;
          -  Expected to require admission to an ICU for ≥ 48 hours&#xD;
&#xD;
          -  Intravenous opioid administration in the prior 24 hours of ≥ 100 mcg fentanyl&#xD;
             equivalents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Scheduled use of an opioid ≥ 10 mg morphine equivalents per day in the week prior to&#xD;
             ICU admission&#xD;
&#xD;
          -  History of constipation (≤ 2 SBM per week and current use of stool softener or&#xD;
             laxative therapy) prior to ICU admission&#xD;
&#xD;
          -  Current scheduled use of a medication affecting gastric motility&#xD;
&#xD;
          -  Current use of a medication known to be a strong CYP3A4 inhibitor&#xD;
&#xD;
          -  History of a neurologic condition that may affect the permeability of the blood-brain&#xD;
             barrier&#xD;
&#xD;
          -  Acute GI condition (e.g., clinical evidence of acute fecal impaction/complete&#xD;
             obstruction, acute surgical abdomen, acute GI bleeding)&#xD;
&#xD;
          -  Condition affecting GI motility or function (e.g. inflammatory bowel disease requiring&#xD;
             immunosuppressive therapy, symptomatic Clostridium difficile, active diverticular&#xD;
             disease, surgery on the colon or abdomen within 60 days of ICU admission)&#xD;
&#xD;
          -  Current use of total parenteral nutrition&#xD;
&#xD;
          -  Administration of enteral nutrition through a jejunal tube&#xD;
&#xD;
          -  Severe hepatic dysfunction&#xD;
&#xD;
          -  Endstage renal disease defined as either i. calculated creatinine clearance ≤ 10ml/min&#xD;
             or ii. Any current use of renal replacement therapy&#xD;
&#xD;
          -  Inability to enroll in study and initiate study medication within 48 hours of the&#xD;
             patient begin first initiated on scheduled IV opioid therapy after ICU admission&#xD;
&#xD;
          -  Unreliable method for enteral, gastric and/or oral medication administration (e.g., no&#xD;
             feeding tube, nasogastric tube is on suction)&#xD;
&#xD;
          -  Current or previous use of an opioid antagonist agent (e.g., naloxegol,&#xD;
             methylnaltrexone) in the past 30 days&#xD;
&#xD;
          -  Pregnant or actively lactating females&#xD;
&#xD;
          -  Current participation in another interventional clinical study&#xD;
&#xD;
          -  Inability to obtain informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Erik Garpestad, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tufts Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, Braun JP, Poeze M, Spies C. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012 Mar;38(3):384-94. doi: 10.1007/s00134-011-2459-y. Epub 2012 Feb 7.</citation>
    <PMID>22310869</PMID>
  </reference>
  <reference>
    <citation>de Azevedo RP, Freitas FG, Ferreira EM, Pontes de Azevedo LC, Machado FR. Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. Crit Care. 2015 Sep 16;19(1):329. doi: 10.1186/s13054-015-1047-x.</citation>
    <PMID>26373705</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 25, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <results_first_submitted>November 22, 2021</results_first_submitted>
  <results_first_submitted_qc>February 15, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 16, 2023</results_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paralysis</mesh_term>
    <mesh_term>Constipation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylnaltrexone</mesh_term>
    <mesh_term>Naloxegol</mesh_term>
    <mesh_term>Bisacodyl</mesh_term>
    <mesh_term>Magnesium citrate</mesh_term>
    <mesh_term>Bismuth subsalicylate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 10, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT02977286/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT02977286/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT02977286/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Naloxegol Oral Tablet</title>
          <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna Oral Tablet, Polyethylene Glycols, Magnesium Citrate Oral Liquid Product, Bisacodyl Suppository and Methylnaltrexone] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
        </group>
        <group group_id="P2">
          <title>Placebo Oral Tablet</title>
          <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Naloxegol Oral Tablet</title>
          <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
        </group>
        <group group_id="B2">
          <title>Placebo Oral Tablet</title>
          <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" spread="23"/>
                    <measurement group_id="B2" value="64" spread="11"/>
                    <measurement group_id="B3" value="57" spread="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40" spread="13"/>
                    <measurement group_id="B2" value="35" spread="16"/>
                    <measurement group_id="B3" value="38" spread="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>APACHE-II: Acute Physiology and Chronic Health Evaluation (version II)</title>
          <description>APACHE II score is a general measure of disease severity based on current physiologic measurements, age and previous health conditions. Minimal score is 0, maximum is 71.&#xD;
Higher value suggests worse outcome.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20" spread="6"/>
                    <measurement group_id="B2" value="19" spread="7"/>
                    <measurement group_id="B3" value="19.5" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>SOFA score: Sequential Organ Failure Assessment Score</title>
          <description>SOFA score is used to track a patient's status, usually during a admission to an Intensive Care Unit. This score tracks patient's organ function or rate of failure. Score is 0 to 24. Higher score is worse, with more organ failure.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8" spread="4"/>
                    <measurement group_id="B2" value="6" spread="2"/>
                    <measurement group_id="B3" value="7" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hours in ICU before enrollment</title>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50" spread="21"/>
                    <measurement group_id="B2" value="44" spread="21"/>
                    <measurement group_id="B3" value="48" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to First Spontaneous Bowel Movement (SBM) Administration</title>
        <description>Time to first spontaneous bowel movement during ICU admission after randomization</description>
        <time_frame>First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Spontaneous Bowel Movement (SBM) Administration</title>
          <description>Time to first spontaneous bowel movement during ICU admission after randomization</description>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41" spread="25"/>
                    <measurement group_id="O2" value="33" spread="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Spontaneous Bowel Movement (SBM)</title>
        <description>Time to first spontaneous bowel movement during the ICU admission after opioid initiation</description>
        <time_frame>First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Spontaneous Bowel Movement (SBM)</title>
          <description>Time to first spontaneous bowel movement during the ICU admission after opioid initiation</description>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52" spread="28"/>
                    <measurement group_id="O2" value="49" spread="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ICU Days Without a SBM</title>
        <description>Measured ICU days that subjects did not have a SBM</description>
        <time_frame>During period of ICU admission or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik&#xD;
.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>ICU Days Without a SBM</title>
          <description>Measured ICU days that subjects did not have a SBM</description>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread="3"/>
                    <measurement group_id="O2" value="2" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)</title>
        <description>Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)</title>
          <description>Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]</title>
        <description>Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]</title>
          <description>Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day</description>
          <units>mcg per day</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1420" lower_limit="65" upper_limit="3548"/>
                    <measurement group_id="O2" value="1600" lower_limit="1105" upper_limit="2382"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Loose and Unformed or Liquid SBM</title>
        <description>Consistency of SBM is characterized in one of 4 categories: hard and formed, soft but formed, loose and unformed, and liquid. The number listed in the results section is the number of patients who had either loose or liquid SBM (as opposed to hard or soft formed).</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Loose and Unformed or Liquid SBM</title>
          <description>Consistency of SBM is characterized in one of 4 categories: hard and formed, soft but formed, loose and unformed, and liquid. The number listed in the results section is the number of patients who had either loose or liquid SBM (as opposed to hard or soft formed).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients That Required Use of the Study Laxative Protocol</title>
        <description>A 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed.</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients That Required Use of the Study Laxative Protocol</title>
          <description>A 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Daily Goal Reached for Enteral Nutrition Administration</title>
        <description>Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Daily Goal Reached for Enteral Nutrition Administration</title>
          <description>Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.</description>
          <units>percentage of daily goals met</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54" spread="34"/>
                    <measurement group_id="O2" value="51" spread="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Fluid Balance</title>
        <description>Daily fluid balance measured in mL is the 24 hours ins and outs</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Fluid Balance</title>
          <description>Daily fluid balance measured in mL is the 24 hours ins and outs</description>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-338" lower_limit="-747" upper_limit="-102"/>
                    <measurement group_id="O2" value="-210" lower_limit="-660" upper_limit="-208"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Maximal Pain Scale Score</title>
        <description>Based on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment.&#xD;
VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain.</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo&#xD;
ation.</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Maximal Pain Scale Score</title>
          <description>Based on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment.&#xD;
VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="3"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Maximal Sedation Assessment Scale (SAS) Score</title>
        <description>The Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present.&#xD;
Results listed here is days without coma (SAS score of 3-7)</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Maximal Sedation Assessment Scale (SAS) Score</title>
          <description>The Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present.&#xD;
Results listed here is days without coma (SAS score of 3-7)</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="1" upper_limit="3"/>
                    <measurement group_id="O2" value="7" lower_limit="4" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)</title>
        <description>Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)</title>
          <description>Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)</description>
          <units>days without delirium</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4" upper_limit="6"/>
                    <measurement group_id="O2" value="6" lower_limit="4" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation</title>
        <description>Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation</description>
        <time_frame>From randomization to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation</title>
          <description>Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Days Without Mechanical Ventilation Support for Duration of ICU Stay</title>
        <description>Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range</description>
        <time_frame>From ICU admission to ICU discharge or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Days Without Mechanical Ventilation Support for Duration of ICU Stay</title>
          <description>Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="0.2" upper_limit="5"/>
                    <measurement group_id="O2" value="1" lower_limit="0.3" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Abdominal Pressure Measurement</title>
        <description>On days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported.</description>
        <time_frame>From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Abdominal Pressure Measurement</title>
          <description>On days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported.</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" spread="4"/>
                    <measurement group_id="O2" value="13" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Episode of Diarrhea</title>
        <description>The number of patients in each group with &gt; or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours.</description>
        <time_frame>Study drug initiation to first episode of diarrhea in hours.</time_frame>
        <population>Number of patients in each group with &gt; or equal to 1 episode of diarrhea.</population>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Episode of Diarrhea</title>
          <description>The number of patients in each group with &gt; or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours.</description>
          <population>Number of patients in each group with &gt; or equal to 1 episode of diarrhea.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40" lower_limit="19" upper_limit="66"/>
                    <measurement group_id="O2" value="109" lower_limit="48" upper_limit="169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score</title>
        <description>Patients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal.</description>
        <time_frame>One hour before the daily study drug administration and 2 hours after the daily study drug administration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Naloxegol Oral Tablet</title>
            <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
          </group>
          <group group_id="O2">
            <title>Placebo Oral Tablet</title>
            <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score</title>
          <description>Patients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal.</description>
          <units>Difference of COWS score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="1.3"/>
                    <measurement group_id="O2" value="0.2" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for each subject during the period from time of study enrollment (i.e. randomization) to ICU discharge, death or 10 days of study drug administration (whatever comes first).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Naloxegol Oral Tablet</title>
          <description>Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: Movantik</description>
        </group>
        <group group_id="E2">
          <title>Placebo Oral Tablet</title>
          <description>Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:&#xD;
Adverse event potentially attributable to the study drug.&#xD;
Use of Relistor.&#xD;
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.&#xD;
The participant has been administered 10 days of study medication.&#xD;
The participant is discharged from the ICU.&#xD;
The participant requires the initiation of a strong CYP3A4 inhibitor medication.&#xD;
Other Name: AstraZeneca provided Movantik placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Diarrhea defined where greater than or equal to 3 loose or watery stools (Bristol stool scale score of 6 or 7) in a 24 hour period.</description>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Limitations: One-third of the planned participants were enrolled, thus the study is substantially underpowered. Our results do not apply to non-medical patients.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Erik Garpestad, M.D.</name_or_title>
      <organization>Tufts Medical Center</organization>
      <phone>617-636-5388</phone>
      <email>egarpestad@tuftsmedicalcenter.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02977286
org study id: 11200
nct id: NCT02977286
lead sponsor: 
has dmc: Yes
This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in
      critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the
      participants will receive naloxegol and a laxative protocol and half the participants will
      receive a placebo and a laxative protocol.
Among the more than 5 million adults who are admitted to the ICU each year in the USA, most
      have pain and thus receive a pain (analgesic) medication called an opioid. Opioid use in
      critically ill adults continues to increase given the greater awareness of untreated pain in
      the ICU and that an opioid-first approach be used to optimize patient safety and comfort and
      improve tolerance with breathing machines (i.e. mechanical ventilation). Similar to
      constipation, paralysis of the lower gastrointestinal (GI) tract is defined as the inability
      to pass stool due to impaired gut movement, and is a common effect of opioid use in the
      critically ill. Lower GI tract paralysis may lead to nausea, vomiting, aspiration, compromise
      the ability to administer tube feeds (enteral nutrition), an increase abdominal pain,
      delirium and delay getting off mechanical ventilation. One recent randomized study found that
      aggressive use of laxatives to prevent lower GI tract paralysis in critically ill adults was
      associated with lower daily organ dysfunction [as measured by the Sequential Organ Failure
      Assessment (SOFA) score]. The lower GI tract paralysis that occurs in the critically ill
      often responds poorly to laxative medication therapy (e.g., senna, bisacodyl, lactulose).
      While stool softener medications like docusate are routinely administered to patients on
      opioids, laxative-based protocols are frequently not initiated in the ICU until signs of
      lower GI tract paralysis start to appear. There is therefore an important and unmet need for
      a safe and efficacious medication to prevent lower GI tract paralysis in critically ill
      adults who are initiated on opioid therapy. Naloxegol (Movantik) is a naloxone-like drug that
      blocks the effect of opioids on the opioid µ receptor in the gut but is not absorbed in the
      brain (and therefore does not block the pain effects of opioids). Naloxegol is currently
      approved by the Food and Drug Administration (FDA) for the treatment of opioid-induced
      constipation (OIC) in non-ICU patients receiving scheduled moderate to high dose opioids for
      the treatment of chronic non-cancer pain. Naloxegol has a mechanism of action, efficacy,
      convenience of administration, and safety profile that make it an ideal candidate for use as
      a preventative medication for lower GI tract paralysis in critically ill adults receiving
      scheduled opioid therapy. The investigators propose a pilot study in which they will test the
      hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous
      bowel movement (SBM) that an ICU patient has, that it will prevent lower GI tract paralysis
      in critically ill adults initiated on scheduled IV opioid therapy, and its use will not
      result in side effects that are concerning to doctors or patients. The investigators will
      randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol [25mg or
      12.5mg (in patients with a creatinine clearance ≤ 60ml/min)] or placebo. This pilot study
      will provide valuable information to help guide future, larger studies evaluating the role of
      naloxegol in critically ill adults.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to First Spontaneous Bowel Movement (SBM) Administration
time frame: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days
description: Time to first spontaneous bowel movement during ICU admission after randomization
measure: Time to First Spontaneous Bowel Movement (SBM)
time frame: First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days
description: Time to first spontaneous bowel movement during the ICU admission after opioid initiation
measure: ICU Days Without a SBM
time frame: During period of ICU admission or a maximum of 10 ICU days
description: Measured ICU days that subjects did not have a SBM
measure: Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame
measure: Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day
measure: Number of Patients With Loose and Unformed or Liquid SBM
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Consistency of SBM is characterized in one of 4 categories: hard and formed, soft but formed, loose and unformed, and liquid. The number listed in the results section is the number of patients who had either loose or liquid SBM (as opposed to hard or soft formed).
measure: Number of Patients That Required Use of the Study Laxative Protocol
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: A 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed.
measure: Percentage of Daily Goal Reached for Enteral Nutrition Administration
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.
measure: Daily Fluid Balance
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Daily fluid balance measured in mL is the 24 hours ins and outs
measure: Daily Maximal Pain Scale Score
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Based on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment.
VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain.
measure: Daily Maximal Sedation Assessment Scale (SAS) Score
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: The Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present.
Results listed here is days without coma (SAS score of 3-7)
measure: Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)
measure: Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation
time frame: From randomization to ICU discharge or a maximum of 10 ICU days
description: Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation
measure: Days Without Mechanical Ventilation Support for Duration of ICU Stay
time frame: From ICU admission to ICU discharge or a maximum of 10 ICU days
description: Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range
measure: Abdominal Pressure Measurement
time frame: From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days
description: On days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported.
measure: Time to First Episode of Diarrhea
time frame: Study drug initiation to first episode of diarrhea in hours.
description: The number of patients in each group with > or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours.
measure: Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score
time frame: One hour before the daily study drug administration and 2 hours after the daily study drug administration
description: Patients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal.
arm group label: Naloxegol Oral Tablet
arm group type: Experimental
description: Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:
Adverse event potentially attributable to the study drug.
Use of Relistor.
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
The participant has been administered 10 days of study medication.
The participant is discharged from the ICU.
The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
arm group label: Placebo Oral Tablet
arm group type: Placebo Comparator
description: Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:
Adverse event potentially attributable to the study drug.
Use of Relistor.
Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
The participant has been administered 10 days of study medication.
The participant is discharged from the ICU.
The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
intervention type: Drug
intervention name: Naloxegol Oral Tablet
description: Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily
arm group label: Naloxegol Oral Tablet
other name: Movantik
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Placebo Oral Tablet po (enteral) twice daily
arm group label: Placebo Oral Tablet
other name: Official AstraZeneca placebo for Movantik
intervention type: Drug
intervention name: Docusate Sodium 100 Mg oral capsule [Colace]
description: Docusate Sodium 100 mg po (enteral) twice daily
arm group label: Naloxegol Oral Tablet
arm group label: Placebo Oral Tablet
other name: Colace
intervention type: Drug
intervention name: Senna 217 Mg Oral Tablet
description: Senna 127 mg oral tablet daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to two senna 127 mg tables if no no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=5 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=6 days after scheduled opioid initiation.
arm group label: Naloxegol Oral Tablet
arm group label: Placebo Oral Tablet
other name: Senokot
intervention type: Drug
intervention name: Polyethylene Glycols
description: Polyethylene Glycols 17 g daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to 34 g daily if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation.
arm group label: Naloxegol Oral Tablet
arm group label: Placebo Oral Tablet
other name: Miralax
intervention type: Drug
intervention name: Bisacodyl 10 mg Suppository
description: Insert one suppository if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation.
arm group label: Naloxegol Oral Tablet
arm group label: Placebo Oral Tablet
other name: Dulcolax
intervention type: Drug
intervention name: Magnesium Citrate Oral Liquid Product
description: Administer one 10 oz bottle if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation.
arm group label: Naloxegol Oral Tablet
arm group label: Placebo Oral Tablet
other name: Citromag
intervention type: Drug
intervention name: Methylnaltrexone
description: Administer 8 mg or 16 mg (depending on subject's weight) subcutaneously x 1 if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation, consult surgery/gastroenterology and discontinue study medication.
arm group label: Naloxegol Oral Tablet
arm group label: Placebo Oral Tablet
other name: Relistor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Erik Garpestad, MD
role: Principal Investigator
affiliation: Tufts Medical Center
facility: 
country: United States
citation: Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, Braun JP, Poeze M, Spies C. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012 Mar;38(3):384-94. doi: 10.1007/s00134-011-2459-y. Epub 2012 Feb 7.
PMID: 22310869
citation: de Azevedo RP, Freitas FG, Ferreira EM, Pontes de Azevedo LC, Machado FR. Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. Crit Care. 2015 Sep 16;19(1):329. doi: 10.1186/s13054-015-1047-x.
PMID: 26373705
responsible party type: Sponsor
mesh term: Paralysis
mesh term: Constipation
mesh term: Methylnaltrexone
mesh term: Naloxegol
mesh term: Bisacodyl
mesh term: Magnesium citrate
mesh term: Bismuth subsalicylate
sharing ipd: No
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Limitations: One-third of the planned participants were enrolled, thus the study is substantially underpowered. Our results do not apply to non-medical patients.
point of contact: 