<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/NCT02218190</url>
  </required_header>
  <id_info>
    <org_study_id>201401126</org_study_id>
    <nct_id>NCT02218190</nct_id>
  </id_info>
  <brief_title>Alvimopan and Ileus in PSF</brief_title>
  <official_title>A Randomized Trial of Alvimopan for the Reduction of Ileus After Long Posterior Spinal Fusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orthopedic Research and Education Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Barnes-Jewish Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine with Alvimopan reduces the incidence of post&#xD;
      operative ileus in patients who undergo posterior spinal fusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Posterior spinal fusion (PSF) is a common orthopaedic procedure associated with a high&#xD;
      incidence of post-operative ileus (POI) and concomitant increased length of hospital stay&#xD;
      (LOHS). POI is exacerbated by high dose opiate consumption often required by these patients&#xD;
      post-operatively. We propose a randomized, double-blinded, placebo-controlled pilot trial&#xD;
      studying the use of alvimopan, a peripherally-acting mu-opioid receptor antagonist known to&#xD;
      reduce POI in bowel resection. We hypothesize that alvimopan will shorten POI in spine fusion&#xD;
      patients without negatively affecting post-operative pain control. Treatment efficacy will be&#xD;
      assessed by recording time to first bowel movement, time to hospital discharge, and&#xD;
      post-operative pain control.&#xD;
&#xD;
      We hypothesize that acute administration of alvimopan, a peripherally-acting mu-opioid&#xD;
      antagonist, shortens the duration of post-operative ileus (POI) in patients undergoing&#xD;
      long-segment (5 or greater thoracolumbar levels) posterior spinal fusion (PSF). The study&#xD;
      will be a randomized, double-blinded, placebo-controlled pilot trial. Reducing the morbidity&#xD;
      of POI in patients undergoing PSF will decrease hospital stay and costs, and also improve&#xD;
      patient satisfaction and post-operative care after major orthopaedic surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">January 2019</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recovery of Bowel Function</measure>
    <time_frame>14 days or until hospital discharge whichever occurs first</time_frame>
    <description>To determine the effect of alvimopan on the recovery of bowel function as determined by time to first bowel movement in patients undergoing posterior spinal fusion. The effect size calculated may guide a larger, multicenter randomized controlled study. Time was measured from wound closure to bowel movement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Length of Hospital Stay</measure>
    <time_frame>14 days or until hospital discharge whichever occurs first</time_frame>
    <description>To determine the effect of alvimopan on overall length of hospital stay in patients undergoing PSF.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complications and Adverse Event</measure>
    <time_frame>14 days or until hospital discharge, which ever occurs first</time_frame>
    <description>Number of patients with complication/adverse event.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Ileus</condition>
  <condition>Spinal Fusion</condition>
  <arm_group>
    <arm_group_label>Alvimopan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo - Sugar Pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alvimopan</intervention_name>
    <arm_group_label>Alvimopan</arm_group_label>
    <other_name>Entereg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo - Sugar Pill</arm_group_label>
    <other_name>Sugar Pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patients undergoing elective PSF of at least 5 levels and/or fixation to pelvis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnant women&#xD;
&#xD;
          -  ischemic heart disease&#xD;
&#xD;
          -  chronic liver or renal disease&#xD;
&#xD;
          -  prior bowel resection&#xD;
&#xD;
          -  presence of colostomy or ileostomy&#xD;
&#xD;
          -  gastroparesis&#xD;
&#xD;
          -  complete bowel obstruction&#xD;
&#xD;
          -  inflammatory bowel disease (ulcerative colitis or Crohn's disease).&#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>Michael P Kelly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Orthopedic Surgery - Washington University in St. Louis School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Barnes Jewish Hospital / Washington University in St. Louis School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2008/021775s000_sumr.pdf</url>
    <description>Summary Review for Regulatory Action</description>
  </link>
  <reference>
    <citation>Kehlet H, Holte K. Review of postoperative ileus. Am J Surg. 2001 Nov;182(5A Suppl):3S-10S. doi: 10.1016/s0002-9610(01)00781-4.</citation>
    <PMID>11755891</PMID>
  </reference>
  <reference>
    <citation>Senagore AJ. Pathogenesis and clinical and economic consequences of postoperative ileus. Am J Health Syst Pharm. 2007 Oct 15;64(20 Suppl 13):S3-7. doi: 10.2146/ajhp070428.</citation>
    <PMID>17909274</PMID>
  </reference>
  <reference>
    <citation>Leslie JB. Alvimopan for the management of postoperative ileus. Ann Pharmacother. 2005 Sep;39(9):1502-10. doi: 10.1345/aph.1E615. Epub 2005 Aug 2.</citation>
    <PMID>16076918</PMID>
  </reference>
  <reference>
    <citation>Holzer P. Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett. 2004 May 6;361(1-3):192-5. doi: 10.1016/j.neulet.2003.12.004.</citation>
    <PMID>15135926</PMID>
  </reference>
  <reference>
    <citation>Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs. 2003;63(7):649-71. doi: 10.2165/00003495-200363070-00003.</citation>
    <PMID>12656645</PMID>
  </reference>
  <reference>
    <citation>Sternini C, Patierno S, Selmer IS, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterol Motil. 2004 Oct;16 Suppl 2:3-16. doi: 10.1111/j.1743-3150.2004.00553.x.</citation>
    <PMID>15357847</PMID>
  </reference>
  <reference>
    <citation>Behm B, Stollman N. Postoperative ileus: etiologies and interventions. Clin Gastroenterol Hepatol. 2003 Mar;1(2):71-80. doi: 10.1053/cgh.2003.50012.</citation>
    <PMID>15017498</PMID>
  </reference>
  <reference>
    <citation>Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg. 2000 Nov;87(11):1480-93. doi: 10.1046/j.1365-2168.2000.01595.x.</citation>
    <PMID>11091234</PMID>
  </reference>
  <reference>
    <citation>Zimmerman DM, Gidda JS, Cantrell BE, Schoepp DD, Johnson BG, Leander JD. Discovery of a potent, peripherally selective trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonist for the treatment of gastrointestinal motility disorders. J Med Chem. 1994 Jul 22;37(15):2262-5. doi: 10.1021/jm00041a003.</citation>
    <PMID>8057274</PMID>
  </reference>
  <reference>
    <citation>Delaney CP, Weese JL, Hyman NH, Bauer J, Techner L, Gabriel K, Du W, Schmidt WK, Wallin BA; Alvimopan Postoperative Ileus Study Group. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Dis Colon Rectum. 2005 Jun;48(6):1114-25; discussion 1125-6; author reply 1127-9. doi: 10.1007/s10350-005-0035-7.</citation>
    <PMID>15906123</PMID>
  </reference>
  <reference>
    <citation>Liu SS, Hodgson PS, Carpenter RL, Fricke JR Jr. ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia. Clin Pharmacol Ther. 2001 Jan;69(1):66-71. doi: 10.1067/mcp.2001.112680.</citation>
    <PMID>11180040</PMID>
  </reference>
  <reference>
    <citation>Viscusi ER, Goldstein S, Witkowski T, Andonakakis A, Jan R, Gabriel K, Du W, Techner L, Wallin B. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study. Surg Endosc. 2006 Jan;20(1):64-70. doi: 10.1007/s00464-005-0104-y. Epub 2005 Dec 7. Erratum In: Surg Endosc. 2006 Mar;20(3):537.</citation>
    <PMID>16333556</PMID>
  </reference>
  <reference>
    <citation>Wolff BG, Michelassi F, Gerkin TM, Techner L, Gabriel K, Du W, Wallin BA; Alvimopan Postoperative Ileus Study Group. Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus. Ann Surg. 2004 Oct;240(4):728-34; discussion 734-5. doi: 10.1097/01.sla.0000141158.27977.66.</citation>
    <PMID>15383800</PMID>
  </reference>
  <reference>
    <citation>Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R. Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Aug 1;28(3):312-25. doi: 10.1111/j.1365-2036.2008.03696.x.</citation>
    <PMID>19086236</PMID>
  </reference>
  <reference>
    <citation>Wolff BG, Viscusi ER, Delaney CP, Du W, Techner L. Patterns of gastrointestinal recovery after bowel resection and total abdominal hysterectomy: pooled results from the placebo arms of alvimopan phase III North American clinical trials. J Am Coll Surg. 2007 Jul;205(1):43-51. doi: 10.1016/j.jamcollsurg.2007.02.026. Epub 2007 May 17.</citation>
    <PMID>17617331</PMID>
  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <results_first_submitted>April 1, 2019</results_first_submitted>
  <results_first_submitted_qc>May 15, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 17, 2019</results_first_posted>
  <last_update_submitted>May 15, 2019</last_update_submitted>
  <last_update_submitted_qc>May 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Michael Kelly</investigator_full_name>
    <investigator_title>Assistant Prof. Department of Orthopedic Surgery</investigator_title>
  </responsible_party>
  <keyword>Alvimopan</keyword>
  <keyword>Ileus</keyword>
  <keyword>Posterior spinal fusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ileus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alvimopan</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>5 Patients enrolled and withdrew prior to undergoing randomization, surgery and treatment</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Alvimopan</title>
          <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.&#xD;
Alvimopan</description>
        </group>
        <group group_id="P2">
          <title>Placebo - Sugar Pill</title>
          <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven&#xD;
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="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </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>Alvimopan</title>
          <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.&#xD;
Alvimopan</description>
        </group>
        <group group_id="B2">
          <title>Placebo - Sugar Pill</title>
          <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven&#xD;
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="13"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="13"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.2" spread="17.5"/>
                    <measurement group_id="B2" value="54.7" spread="13.7"/>
                    <measurement group_id="B3" value="52.0" spread="15.6"/>
                  </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="13"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Recovery of Bowel Function</title>
        <description>To determine the effect of alvimopan on the recovery of bowel function as determined by time to first bowel movement in patients undergoing posterior spinal fusion. The effect size calculated may guide a larger, multicenter randomized controlled study. Time was measured from wound closure to bowel movement.</description>
        <time_frame>14 days or until hospital discharge whichever occurs first</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alvimopan</title>
            <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.&#xD;
Alvimopan</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Sugar Pill</title>
            <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Recovery of Bowel Function</title>
          <description>To determine the effect of alvimopan on the recovery of bowel function as determined by time to first bowel movement in patients undergoing posterior spinal fusion. The effect size calculated may guide a larger, multicenter randomized controlled study. Time was measured from wound closure to bowel movement.</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="13"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.2" spread="23.1"/>
                    <measurement group_id="O2" value="34.0" spread="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Length of Hospital Stay</title>
        <description>To determine the effect of alvimopan on overall length of hospital stay in patients undergoing PSF.</description>
        <time_frame>14 days or until hospital discharge whichever occurs first</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alvimopan</title>
            <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.&#xD;
Alvimopan</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Sugar Pill</title>
            <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Hospital Stay</title>
          <description>To determine the effect of alvimopan on overall length of hospital stay in patients undergoing PSF.</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="13"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122.5" spread="48.4"/>
                    <measurement group_id="O2" value="117.2" spread="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complications and Adverse Event</title>
        <description>Number of patients with complication/adverse event.</description>
        <time_frame>14 days or until hospital discharge, which ever occurs first</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alvimopan</title>
            <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.&#xD;
Alvimopan</description>
          </group>
          <group group_id="O2">
            <title>Placebo - Sugar Pill</title>
            <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Complications and Adverse Event</title>
          <description>Number of patients with complication/adverse event.</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="13"/>
                <count group_id="O2" value="13"/>
              </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_list>

    <reported_events>
      <time_frame>Adverse events were collected up to 6 weeks after surgery.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Alvimopan</title>
          <description>Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.&#xD;
Alvimopan</description>
        </group>
        <group group_id="E2">
          <title>Placebo - Sugar Pill</title>
          <description>Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Venothromboembolic Event</sub_title>
                <description>Unrelated to intervention</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Postoperative Hematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Screw malposition</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <point_of_contact>
      <name_or_title>Michael P. Kelly, MD, MSc</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-747-2511</phone>
      <email>kellymi@wustl.edu</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/NCT02218190
org study id: 201401126
nct id: NCT02218190
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of the study is to determine with Alvimopan reduces the incidence of post
      operative ileus in patients who undergo posterior spinal fusion.
Posterior spinal fusion (PSF) is a common orthopaedic procedure associated with a high
      incidence of post-operative ileus (POI) and concomitant increased length of hospital stay
      (LOHS). POI is exacerbated by high dose opiate consumption often required by these patients
      post-operatively. We propose a randomized, double-blinded, placebo-controlled pilot trial
      studying the use of alvimopan, a peripherally-acting mu-opioid receptor antagonist known to
      reduce POI in bowel resection. We hypothesize that alvimopan will shorten POI in spine fusion
      patients without negatively affecting post-operative pain control. Treatment efficacy will be
      assessed by recording time to first bowel movement, time to hospital discharge, and
      post-operative pain control.

      We hypothesize that acute administration of alvimopan, a peripherally-acting mu-opioid
      antagonist, shortens the duration of post-operative ileus (POI) in patients undergoing
      long-segment (5 or greater thoracolumbar levels) posterior spinal fusion (PSF). The study
      will be a randomized, double-blinded, placebo-controlled pilot trial. Reducing the morbidity
      of POI in patients undergoing PSF will decrease hospital stay and costs, and also improve
      patient satisfaction and post-operative care after major orthopaedic surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Recovery of Bowel Function
time frame: 14 days or until hospital discharge whichever occurs first
description: To determine the effect of alvimopan on the recovery of bowel function as determined by time to first bowel movement in patients undergoing posterior spinal fusion. The effect size calculated may guide a larger, multicenter randomized controlled study. Time was measured from wound closure to bowel movement.
measure: Length of Hospital Stay
time frame: 14 days or until hospital discharge whichever occurs first
description: To determine the effect of alvimopan on overall length of hospital stay in patients undergoing PSF.
measure: Complications and Adverse Event
time frame: 14 days or until hospital discharge, which ever occurs first
description: Number of patients with complication/adverse event.
arm group label: Alvimopan
arm group type: Experimental
description: Alvimopan 12mg once orally two hours prior to surgery and then 2 mg orally twice a day until post-operative day (POD) seven.
arm group label: Placebo - Sugar Pill
arm group type: Placebo Comparator
description: Placebo Sugar Pill orally two hours prior to surgery and then one sugar pill orally twice a day until post-operative day (POD) seven
intervention type: Drug
intervention name: Alvimopan
arm group label: Alvimopan
other name: Entereg
intervention type: Drug
intervention name: Placebo
arm group label: Placebo - Sugar Pill
other name: Sugar Pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael P Kelly, MD
role: Principal Investigator
affiliation: Department of Orthopedic Surgery - Washington University in St. Louis School of Medicine
facility: 
country: United States
url: https://www.accessdata.fda.gov/drugsatfda_docs/summary_review/2008/021775s000_sumr.pdf
description: Summary Review for Regulatory Action
citation: Kehlet H, Holte K. Review of postoperative ileus. Am J Surg. 2001 Nov;182(5A Suppl):3S-10S. doi: 10.1016/s0002-9610(01)00781-4.
PMID: 11755891
citation: Senagore AJ. Pathogenesis and clinical and economic consequences of postoperative ileus. Am J Health Syst Pharm. 2007 Oct 15;64(20 Suppl 13):S3-7. doi: 10.2146/ajhp070428.
PMID: 17909274
citation: Leslie JB. Alvimopan for the management of postoperative ileus. Ann Pharmacother. 2005 Sep;39(9):1502-10. doi: 10.1345/aph.1E615. Epub 2005 Aug 2.
PMID: 16076918
citation: Holzer P. Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett. 2004 May 6;361(1-3):192-5. doi: 10.1016/j.neulet.2003.12.004.
PMID: 15135926
citation: Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs. 2003;63(7):649-71. doi: 10.2165/00003495-200363070-00003.
PMID: 12656645
citation: Sternini C, Patierno S, Selmer IS, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterol Motil. 2004 Oct;16 Suppl 2:3-16. doi: 10.1111/j.1743-3150.2004.00553.x.
PMID: 15357847
citation: Behm B, Stollman N. Postoperative ileus: etiologies and interventions. Clin Gastroenterol Hepatol. 2003 Mar;1(2):71-80. doi: 10.1053/cgh.2003.50012.
PMID: 15017498
citation: Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg. 2000 Nov;87(11):1480-93. doi: 10.1046/j.1365-2168.2000.01595.x.
PMID: 11091234
citation: Zimmerman DM, Gidda JS, Cantrell BE, Schoepp DD, Johnson BG, Leander JD. Discovery of a potent, peripherally selective trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonist for the treatment of gastrointestinal motility disorders. J Med Chem. 1994 Jul 22;37(15):2262-5. doi: 10.1021/jm00041a003.
PMID: 8057274
citation: Delaney CP, Weese JL, Hyman NH, Bauer J, Techner L, Gabriel K, Du W, Schmidt WK, Wallin BA; Alvimopan Postoperative Ileus Study Group. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Dis Colon Rectum. 2005 Jun;48(6):1114-25; discussion 1125-6; author reply 1127-9. doi: 10.1007/s10350-005-0035-7.
PMID: 15906123
citation: Liu SS, Hodgson PS, Carpenter RL, Fricke JR Jr. ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia. Clin Pharmacol Ther. 2001 Jan;69(1):66-71. doi: 10.1067/mcp.2001.112680.
PMID: 11180040
citation: Viscusi ER, Goldstein S, Witkowski T, Andonakakis A, Jan R, Gabriel K, Du W, Techner L, Wallin B. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study. Surg Endosc. 2006 Jan;20(1):64-70. doi: 10.1007/s00464-005-0104-y. Epub 2005 Dec 7. Erratum In: Surg Endosc. 2006 Mar;20(3):537.
PMID: 16333556
citation: Wolff BG, Michelassi F, Gerkin TM, Techner L, Gabriel K, Du W, Wallin BA; Alvimopan Postoperative Ileus Study Group. Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus. Ann Surg. 2004 Oct;240(4):728-34; discussion 734-5. doi: 10.1097/01.sla.0000141158.27977.66.
PMID: 15383800
citation: Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R. Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Aug 1;28(3):312-25. doi: 10.1111/j.1365-2036.2008.03696.x.
PMID: 19086236
citation: Wolff BG, Viscusi ER, Delaney CP, Du W, Techner L. Patterns of gastrointestinal recovery after bowel resection and total abdominal hysterectomy: pooled results from the placebo arms of alvimopan phase III North American clinical trials. J Am Coll Surg. 2007 Jul;205(1):43-51. doi: 10.1016/j.jamcollsurg.2007.02.026. Epub 2007 May 17.
PMID: 17617331
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Michael Kelly
investigator title: Assistant Prof. Department of Orthopedic Surgery
mesh term: Ileus
mesh term: Alvimopan
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 