<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/NCT03241485</url>
  </required_header>
  <id_info>
    <org_study_id>IRB17-1103</org_study_id>
    <nct_id>NCT03241485</nct_id>
  </id_info>
  <brief_title>Trial Comparing Intrathecal Morphine With Placebo In Patients Undergoing Robotic Cardiac Surgery</brief_title>
  <official_title>Randomized, Double Blinded, Trial Comparing Intrathecal Morphine With Placebo in Patients Undergoing Robotic Totally Endoscopic Beating Heart Coronary Revascularization and Intraoperative Extubation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Chicago</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized clinical trial in patients undergoing robotic myocardial&#xD;
      revascularization with intraoperative extubation. Patients will be randomized into placebo or&#xD;
      intrathecal morphine groups to assess postoperative pain scores and patient satisfaction.&#xD;
      Patients will also be assessed for side effects from the intervention.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following Institutional Review Board approval and informed patient consent, 120 patients&#xD;
      scheduled for elective robotic myocardial revascularization without cardiopulmonary bypass&#xD;
      and anticipated intraoperative tracheal extubation will be studied. Patients will be&#xD;
      randomized into one of two groups. Group A (placebo, control group) will receive intrathecal&#xD;
      normal saline, Group B (morphine group) intrathecal morphine. All procedures will occur and&#xD;
      administered medications given immediately prior to induction of general anesthesia in the&#xD;
      operating room. Power analysis indicates that 60 patients per Group is appropriate, as&#xD;
      further described below. Inclusion criteria include any patient undergoing elective robotic&#xD;
      myocardial revascularization without anticipated use of cardiopulmonary bypass and with&#xD;
      anticipated intraoperative tracheal extubation. Exclusion criteria include emergency surgery,&#xD;
      ejection fraction less than 40%, preoperative use of inotropic agents or intraaortic balloon&#xD;
      pump, anticipated use of cardiopulmonary bypass, previous cardiothoracic surgery, anticipated&#xD;
      postoperative tracheal intubation, severe pulmonary disease, morbid obesity (BMI &gt;35 kg/m2),&#xD;
      severe renal dysfunction (creatinine &gt; 1.5) recent history of opioid abuse, preoperative use&#xD;
      of opioids, or any contraindication to intrathecal injection (patient refusal, difficult&#xD;
      patient anatomy, pre-existing coagulopathy, morphine allergy).&#xD;
&#xD;
      Routine preoperative data will be collected (see Preoperative Data Sheet). Following&#xD;
      intravenous access and routine mild sedation, each patient will be transported to the&#xD;
      operating room and assume the sitting position. Following routine skin preparation, a routine&#xD;
      lumbar intrathecal injection will be made via a 22-g spinal needle. The injectate will be&#xD;
      either morphine (5 mcg/kg, maximum dose of 1 mg) or normal saline. The injectate will be&#xD;
      prepared by a co-Investigator not directly involved in patient care. Thus, all preoperative,&#xD;
      intraoperative, and postoperative caregivers will be blinded to intrathecal injectate&#xD;
      composition (all injectates will be standardized to a total of 1.0 ml). All patients will&#xD;
      have port incisions injected with 60 ml of 0.25% bupivacaine by the surgeon after the&#xD;
      completion of surgery.&#xD;
&#xD;
      Following intrathecal injection, the patient will then assume the supine position. An&#xD;
      arterial catheter will be inserted and general endotracheal anesthesia will be induced.&#xD;
      Intraoperative anesthetic technique will be standardized and equivalent between Groups (see&#xD;
      Intraoperative Anesthetic Protocol Sheet). The anesthetic protocol will allow tracheal&#xD;
      extubation to occur in the operating room immediately after surgery (if clinically&#xD;
      indicated).&#xD;
&#xD;
      Surgical technique will not be altered in any way. All patients in both Groups will be&#xD;
      operated on by the same surgeon. Routine intraoperative data will be collected (see&#xD;
      Intraoperative Data Sheet). In all patients, tracheal extubation will be attempted in the&#xD;
      operating room immediately after surgery (if clinically indicated).&#xD;
&#xD;
      Both Groups will receive routine postoperative care and identical postoperative analgesic&#xD;
      protocols to assess adequacy of postoperative analgesia (see Postoperative Analgesia Protocol&#xD;
      and Postoperative Data Sheets). The American Pain Society Outcome Questionnaire (APS-POQ)&#xD;
      will be administered to patients prior to discharge (see data sheet).15&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 19, 2018</start_date>
  <completion_date type="Actual">September 1, 2020</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>The patients will be randomized into 2 groups. The placebo group will receive intrathecal saline. The morphine group will receive intrathecal morphine.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All patients will receive intrathecal intervention and will not know which group they are assigned to. The provider performing the procedure and collecting the data will also be blinded to the intervention assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Postoperative Morphine Consumption</measure>
    <time_frame>24 hours after surgery</time_frame>
    <description>We anticipate that patients in the intervention groups will require less postoperative morphine for pain control.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Score</measure>
    <time_frame>First 48 hours after surgery</time_frame>
    <description>Patients will score their pain on a visual analog scale of 0-10. The higher the score, the worse the patients reported pain is at that time .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Satisfaction</measure>
    <time_frame>1-3 days after surgery, prior to discharge.</time_frame>
    <description>Patients will take a satisfaction survey prior to discharge, this is measured by calculating a score on a scale. This survey consist of questions that asks about the subjects post-operative experience with pain. Higher reported scores represent worse post-operative subject experience. These are ranked from a 0-10 scale, where 0 is the best experience and 10 meaning the worst experience. Questions being asked how satisfied they were with the results of the pain treatment while hospitalized, least pain in prior 24 hours, worst pain in prior 24 ours, percent time in severe pain, how much pain interfered with different activities, how much pain caused anxiety, depression, fright, helplessness, how severe were symptoms of nausea, drowsiness, itching, dizziness, and percentage pain relief in prior 24 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Nausea</measure>
    <time_frame>Until discharge, 2-3 days after surgery</time_frame>
    <description>Daily evaluation of nausea post-operatively throughout the subjects hospital stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Respiratory Depression</measure>
    <time_frame>During hospital stay</time_frame>
    <description>Opioid related respiratory depression, post-operatively throughout the subjects hospital stay.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>60 patients will be randomly assigned to this arm. The patients in this arm will receive intrathecal saline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intrathecal morphine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>60 patients will be randomly assigned to this arm. The patients in this arm will receive intrathecal morphine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intrathecal morphine</intervention_name>
    <description>5 micrograms/kilogram of intrathecal morphine administered in the spinal space, not to exceed 1mg</description>
    <arm_group_label>Intrathecal morphine</arm_group_label>
    <other_name>Duramorph</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Saline intrathecal given in the same manner as the intervention groups.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • patient undergoing elective robotic myocardial revascularization without anticipated use&#xD;
        of cardiopulmonary bypass and with anticipated intraoperative tracheal extubation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Emergency surgery&#xD;
&#xD;
          -  Preoperative use of inotropes/IABP&#xD;
&#xD;
          -  Preoperative use of opoids&#xD;
&#xD;
          -  Ejection fraction less than 40%&#xD;
&#xD;
          -  Anticipated use of cardiopulmonary bypass&#xD;
&#xD;
          -  Previous cardiothoracic surgery&#xD;
&#xD;
          -  Anticipated postoperative tracheal intubation&#xD;
&#xD;
          -  severe pulmonary disease&#xD;
&#xD;
          -  morbid obesity (BMI &gt;35 kg/m2)&#xD;
&#xD;
          -  severe hepatic impairment&#xD;
&#xD;
          -  severe renal dysfunction (creatinine &gt; 1.5)&#xD;
&#xD;
          -  any contraindication to intrathecal injection (patient refusal, difficult patient&#xD;
             anatomy, pre-existing coagulopathy, morphine allergy)&#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>Richa Dhawan, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Chicago Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>May 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <results_first_submitted>August 17, 2021</results_first_submitted>
  <results_first_submitted_qc>October 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 23, 2021</results_first_posted>
  <last_update_submitted>October 26, 2021</last_update_submitted>
  <last_update_submitted_qc>October 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT03241485/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>42 patients were randomized to the intrathecal placebo group. This group received a normal saline injected in the spinal spice, prior to surgery.</description>
        </group>
        <group group_id="P2">
          <title>Intrathecal Morphine</title>
          <description>37 patients were randomized to the intrathecal morphine group. This group received 5 micrograms/kilogram of intrathecal morphine administered in the spinal space</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>42 patients were randomized to this group</description>
        </group>
        <group group_id="B2">
          <title>Intrathecal Morphine</title>
          <description>37 patients were randomized to this group</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="42"/>
            <count group_id="B2" value="37"/>
            <count group_id="B3" value="79"/>
          </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="42"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="79"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.5" spread="10"/>
                    <measurement group_id="B2" value="67.3" spread="10.5"/>
                    <measurement group_id="B3" value="65.8" spread="10.2"/>
                  </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="42"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="79"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="65"/>
                  </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>Weight</title>
          <units>KG</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="42"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="79"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="87" spread="14"/>
                    <measurement group_id="B2" value="85" spread="14"/>
                    <measurement group_id="B3" value="86.4" spread="14.2"/>
                  </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="42"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="79"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.6" spread="3.6"/>
                    <measurement group_id="B2" value="27.5" spread="3.2"/>
                    <measurement group_id="B3" value="28" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA Physical Status</title>
          <description>ASA Physical status is a medical grading system in which it can help predict a patients perioperative risks. The higher the number, the most at risk the patient is and possibility of a worse outcome. ASA grading scale Ranges from 1-6</description>
          <units>Units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="42"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="79"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="B2" value="3" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="B3" value="3" lower_limit="3" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EuroSCORE II</title>
          <description>The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II. Predicts risk of in-hospital mortality after major cardiac surgery. This is calculated on a score on a scale by entering several different information of the patient into the Euroscore II calculator. These include demographic, lab values, medical history.&#xD;
The higher a patients total score is, the likelihood of post-operative mortality after cardiac surgery is. With a range from 0-21. With 0 meaning there there is no risk of in-hospital mortality after major cardiac surgery and 21 meaning there is a severe high risk.</description>
          <units>Scores 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="42"/>
                    <count group_id="B2" value="37"/>
                    <count group_id="B3" value="79"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1" spread="0.5"/>
                    <measurement group_id="B2" value="1" spread="0.5"/>
                    <measurement group_id="B3" value="1" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Postoperative Morphine Consumption</title>
        <description>We anticipate that patients in the intervention groups will require less postoperative morphine for pain control.</description>
        <time_frame>24 hours after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>36 patients were analyzed for primary outcome. One patient did not receive allocated intervention (failed spinal), One PCA data was lost, and 4 patients remained intubated overnight.</description>
          </group>
          <group group_id="O2">
            <title>Morphine</title>
            <description>Intrathecal morphine group</description>
          </group>
        </group_list>
        <measure>
          <title>Postoperative Morphine Consumption</title>
          <description>We anticipate that patients in the intervention groups will require less postoperative morphine for pain control.</description>
          <units>Miligram</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="36"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59" lower_limit="41" upper_limit="79"/>
                    <measurement group_id="O2" value="28" lower_limit="16" upper_limit="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Score</title>
        <description>Patients will score their pain on a visual analog scale of 0-10. The higher the score, the worse the patients reported pain is at that time .</description>
        <time_frame>First 48 hours after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intrathecal saline group</description>
          </group>
          <group group_id="O2">
            <title>Morphine</title>
            <description>Intrathecal Morphine Group</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Score</title>
          <description>Patients will score their pain on a visual analog scale of 0-10. The higher the score, the worse the patients reported pain is at that time .</description>
          <units>score on a scale</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="37"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="4.5" upper_limit="8"/>
                    <measurement group_id="O2" value="1.2" lower_limit="0" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Satisfaction</title>
        <description>Patients will take a satisfaction survey prior to discharge, this is measured by calculating a score on a scale. This survey consist of questions that asks about the subjects post-operative experience with pain. Higher reported scores represent worse post-operative subject experience. These are ranked from a 0-10 scale, where 0 is the best experience and 10 meaning the worst experience. Questions being asked how satisfied they were with the results of the pain treatment while hospitalized, least pain in prior 24 hours, worst pain in prior 24 ours, percent time in severe pain, how much pain interfered with different activities, how much pain caused anxiety, depression, fright, helplessness, how severe were symptoms of nausea, drowsiness, itching, dizziness, and percentage pain relief in prior 24 hours.</description>
        <time_frame>1-3 days after surgery, prior to discharge.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intrathecal saline group</description>
          </group>
          <group group_id="O2">
            <title>Morphine</title>
            <description>Intrathecal Morphine Group</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Satisfaction</title>
          <description>Patients will take a satisfaction survey prior to discharge, this is measured by calculating a score on a scale. This survey consist of questions that asks about the subjects post-operative experience with pain. Higher reported scores represent worse post-operative subject experience. These are ranked from a 0-10 scale, where 0 is the best experience and 10 meaning the worst experience. Questions being asked how satisfied they were with the results of the pain treatment while hospitalized, least pain in prior 24 hours, worst pain in prior 24 ours, percent time in severe pain, how much pain interfered with different activities, how much pain caused anxiety, depression, fright, helplessness, how severe were symptoms of nausea, drowsiness, itching, dizziness, and percentage pain relief in prior 24 hours.</description>
          <units>score on a scale</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="28"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="7" upper_limit="10"/>
                    <measurement group_id="O2" value="9.5" lower_limit="6.5" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Nausea</title>
        <description>Daily evaluation of nausea post-operatively throughout the subjects hospital stay.</description>
        <time_frame>Until discharge, 2-3 days after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Nausea)</title>
            <description>Intrathecal saline group</description>
          </group>
          <group group_id="O2">
            <title>Morphine</title>
            <description>Intrathecal Morphine group</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Nausea</title>
          <description>Daily evaluation of nausea post-operatively throughout the subjects hospital stay.</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="37"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Respiratory Depression</title>
        <description>Opioid related respiratory depression, post-operatively throughout the subjects hospital stay.</description>
        <time_frame>During hospital stay</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Intrathecal saline group</description>
          </group>
          <group group_id="O2">
            <title>Morphine</title>
            <description>Intrathecal Morphine group</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Respiratory Depression</title>
          <description>Opioid related respiratory depression, post-operatively throughout the subjects hospital stay.</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="37"/>
                <count group_id="O2" value="33"/>
              </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>Each subject was assessed for adverse events throughout their hospital stay, on average this was 1-2 days per participant.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Intrathecal Saline Group</description>
        </group>
        <group group_id="E2">
          <title>Morphine</title>
          <description>5 micrograms/kilogram of intrathecal morphine.</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="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </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="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="37"/>
              </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>
    <point_of_contact>
      <name_or_title>Richa Dhawan</name_or_title>
      <organization>University of Chicago Medicine</organization>
      <phone>773-702-1000</phone>
      <email>rdhawan@dacc.uchicago.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/NCT03241485
org study id: IRB17-1103
nct id: NCT03241485
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized clinical trial in patients undergoing robotic myocardial
      revascularization with intraoperative extubation. Patients will be randomized into placebo or
      intrathecal morphine groups to assess postoperative pain scores and patient satisfaction.
      Patients will also be assessed for side effects from the intervention.
Following Institutional Review Board approval and informed patient consent, 120 patients
      scheduled for elective robotic myocardial revascularization without cardiopulmonary bypass
      and anticipated intraoperative tracheal extubation will be studied. Patients will be
      randomized into one of two groups. Group A (placebo, control group) will receive intrathecal
      normal saline, Group B (morphine group) intrathecal morphine. All procedures will occur and
      administered medications given immediately prior to induction of general anesthesia in the
      operating room. Power analysis indicates that 60 patients per Group is appropriate, as
      further described below. Inclusion criteria include any patient undergoing elective robotic
      myocardial revascularization without anticipated use of cardiopulmonary bypass and with
      anticipated intraoperative tracheal extubation. Exclusion criteria include emergency surgery,
      ejection fraction less than 40%, preoperative use of inotropic agents or intraaortic balloon
      pump, anticipated use of cardiopulmonary bypass, previous cardiothoracic surgery, anticipated
      postoperative tracheal intubation, severe pulmonary disease, morbid obesity (BMI >35 kg/m2),
      severe renal dysfunction (creatinine > 1.5) recent history of opioid abuse, preoperative use
      of opioids, or any contraindication to intrathecal injection (patient refusal, difficult
      patient anatomy, pre-existing coagulopathy, morphine allergy).

      Routine preoperative data will be collected (see Preoperative Data Sheet). Following
      intravenous access and routine mild sedation, each patient will be transported to the
      operating room and assume the sitting position. Following routine skin preparation, a routine
      lumbar intrathecal injection will be made via a 22-g spinal needle. The injectate will be
      either morphine (5 mcg/kg, maximum dose of 1 mg) or normal saline. The injectate will be
      prepared by a co-Investigator not directly involved in patient care. Thus, all preoperative,
      intraoperative, and postoperative caregivers will be blinded to intrathecal injectate
      composition (all injectates will be standardized to a total of 1.0 ml). All patients will
      have port incisions injected with 60 ml of 0.25% bupivacaine by the surgeon after the
      completion of surgery.

      Following intrathecal injection, the patient will then assume the supine position. An
      arterial catheter will be inserted and general endotracheal anesthesia will be induced.
      Intraoperative anesthetic technique will be standardized and equivalent between Groups (see
      Intraoperative Anesthetic Protocol Sheet). The anesthetic protocol will allow tracheal
      extubation to occur in the operating room immediately after surgery (if clinically
      indicated).

      Surgical technique will not be altered in any way. All patients in both Groups will be
      operated on by the same surgeon. Routine intraoperative data will be collected (see
      Intraoperative Data Sheet). In all patients, tracheal extubation will be attempted in the
      operating room immediately after surgery (if clinically indicated).

      Both Groups will receive routine postoperative care and identical postoperative analgesic
      protocols to assess adequacy of postoperative analgesia (see Postoperative Analgesia Protocol
      and Postoperative Data Sheets). The American Pain Society Outcome Questionnaire (APS-POQ)
      will be administered to patients prior to discharge (see data sheet).15
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The patients will be randomized into 2 groups. The placebo group will receive intrathecal saline. The morphine group will receive intrathecal morphine.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All patients will receive intrathecal intervention and will not know which group they are assigned to. The provider performing the procedure and collecting the data will also be blinded to the intervention assignment.
measure: Postoperative Morphine Consumption
time frame: 24 hours after surgery
description: We anticipate that patients in the intervention groups will require less postoperative morphine for pain control.
measure: Pain Score
time frame: First 48 hours after surgery
description: Patients will score their pain on a visual analog scale of 0-10. The higher the score, the worse the patients reported pain is at that time .
measure: Patient Satisfaction
time frame: 1-3 days after surgery, prior to discharge.
description: Patients will take a satisfaction survey prior to discharge, this is measured by calculating a score on a scale. This survey consist of questions that asks about the subjects post-operative experience with pain. Higher reported scores represent worse post-operative subject experience. These are ranked from a 0-10 scale, where 0 is the best experience and 10 meaning the worst experience. Questions being asked how satisfied they were with the results of the pain treatment while hospitalized, least pain in prior 24 hours, worst pain in prior 24 ours, percent time in severe pain, how much pain interfered with different activities, how much pain caused anxiety, depression, fright, helplessness, how severe were symptoms of nausea, drowsiness, itching, dizziness, and percentage pain relief in prior 24 hours.
measure: Number of Participants With Nausea
time frame: Until discharge, 2-3 days after surgery
description: Daily evaluation of nausea post-operatively throughout the subjects hospital stay.
measure: Number of Participants With Respiratory Depression
time frame: During hospital stay
description: Opioid related respiratory depression, post-operatively throughout the subjects hospital stay.
arm group label: Placebo
arm group type: Placebo Comparator
description: 60 patients will be randomly assigned to this arm. The patients in this arm will receive intrathecal saline.
arm group label: Intrathecal morphine
arm group type: Active Comparator
description: 60 patients will be randomly assigned to this arm. The patients in this arm will receive intrathecal morphine.
intervention type: Drug
intervention name: Intrathecal morphine
description: 5 micrograms/kilogram of intrathecal morphine administered in the spinal space, not to exceed 1mg
arm group label: Intrathecal morphine
other name: Duramorph
intervention type: Drug
intervention name: Placebo
description: Saline intrathecal given in the same manner as the intervention groups.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richa Dhawan, MD, MPH
role: Principal Investigator
affiliation: University of Chicago Hospital
facility: 
country: United States
responsible party type: Sponsor
mesh term: Morphine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 