<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/NCT02994940</url>
  </required_header>
  <id_info>
    <org_study_id>948256</org_study_id>
    <nct_id>NCT02994940</nct_id>
  </id_info>
  <brief_title>Modified Pre-operative Oral Doses Acetaminophen Versus Intravenous Acetaminophen</brief_title>
  <acronym>MODIV-APAP</acronym>
  <official_title>Modified Pre-operative Oral Doses Acetaminophen Versus Intravenous Acetaminophen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Davis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acetaminophen is frequently used as an adjunct for pain management in pediatric surgical&#xD;
      patients. The drug is available in an over the counter, inexpensive oral form as well as a&#xD;
      considerably more expensive intravenous form. This study will compare opioid requirements and&#xD;
      acetaminophen plasma levels post operatively for two dosing regimens to compare oral versus&#xD;
      intravenous routes given pre operatively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary purpose of this study is to compare opioid utilization in post-operative patients&#xD;
      undergoing tonsillectomy and adenoidectomy, between IV and PO acetaminophen. Secondarily, it&#xD;
      will provide information regarding possible cost savings, pharmacokinetics and safety between&#xD;
      these two regimens.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Actual">July 3, 2019</completion_date>
  <primary_completion_date type="Actual">July 3, 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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Dose of Opioid</measure>
    <time_frame>Within 24hrs</time_frame>
    <description>Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients With Severe Pain Score of 7 or Higher</measure>
    <time_frame>24 hrs period following surgery</time_frame>
    <description>A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Acetaminophen Level 1 - End of Surgery</measure>
    <time_frame>at the end of surgery, about 1 hour after IV Dose</time_frame>
    <description>mg/L acetaminophen in the plasma at the end of surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration</measure>
    <time_frame>Outcome will be measured 3hrs post first IV Dose</time_frame>
    <description>mg/L acetaminophen in the plasma 3 hours after IV study drug administration</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Tonsillectomy</condition>
  <condition>Adenoidectomy</condition>
  <arm_group>
    <arm_group_label>Oral Acetaminophen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous Acetaminophen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen</intervention_name>
    <description>already included in arm/group descriptions</description>
    <arm_group_label>Intravenous Acetaminophen</arm_group_label>
    <arm_group_label>Oral Acetaminophen</arm_group_label>
    <other_name>OFIRMEV</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ages 3 years to 17 years scheduled for tonsillectomy and adenoidectomy for&#xD;
             obstructive sleep apnea with or without additional minor procedures such as sleep&#xD;
             endoscopy, unilateral or bilateral myringotomy, insertion of tympanostomy tubes and/or&#xD;
             ear exam. ( Minor additional procedures that are frequently combined with&#xD;
             tonsillectomy and adenoidectomy but are not commonly considered to have pain that is&#xD;
             significantly greater than the tonsillectomy and adenoidectomy).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who meet University of California Davis Children's Hospital (UCDCH) criteria&#xD;
             for Pediatric Intensive Care Unit (PICU) admission: on home oxygen pre-operatively,&#xD;
             exhibit airway obstruction when awake (stertor above larynx, stridor at larynx), sleep&#xD;
             study with apnea hypoxia index greater than 25 or sleep oxygen saturation nadir &lt;80%,&#xD;
             cardiac disease, difficult intubation.&#xD;
&#xD;
          -  Patients with a known allergy to acetaminophen&#xD;
&#xD;
          -  Patients with known hepatic insufficiency or severe hepatic disease&#xD;
&#xD;
          -  Patients with known Glucose-6-phosphate dehydrogenase (G6PD) deficiency&#xD;
&#xD;
          -  Patients who are malnourished (ie lower levels of glutathione)&#xD;
&#xD;
          -  Patients with severe renal impairment as defined by calculated creatinine clearance&#xD;
             &lt;20 ml/min (per modified Schwarz equation)&#xD;
&#xD;
          -  Patients who are pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cathy Lammers, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UC Davis Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Davis Children's Hospital</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <results_first_submitted>November 3, 2020</results_first_submitted>
  <results_first_submitted_qc>December 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 9, 2020</results_first_posted>
  <last_update_submitted>January 28, 2021</last_update_submitted>
  <last_update_submitted_qc>January 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 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>Acetaminophen</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>November 18, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT02994940/Prot_SAP_000.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>August 2, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT02994940/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Oral Acetaminophen</title>
          <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
        </group>
        <group group_id="P2">
          <title>Intravenous Acetaminophen</title>
          <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Did not receive study medications: Study drug not available prior to anesthesia induction</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive study medications: vomited after ingestion</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not receive study medications: red dye allergy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Completed subjects (n=66) used for analysis</population>
      <group_list>
        <group group_id="B1">
          <title>Oral Acetaminophen</title>
          <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
        </group>
        <group group_id="B2">
          <title>Intravenous Acetaminophen</title>
          <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</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="30"/>
            <count group_id="B2" value="36"/>
            <count group_id="B3" value="66"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</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="30"/>
                    <count group_id="B2" value="36"/>
                    <count group_id="B3" value="66"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4" lower_limit="4" upper_limit="8"/>
                    <measurement group_id="B2" value="6" lower_limit="4.3" upper_limit="7"/>
                    <measurement group_id="B3" value="5" lower_limit="4" upper_limit="7.25"/>
                  </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="30"/>
                    <count group_id="B2" value="36"/>
                    <count group_id="B3" value="66"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="37"/>
                  </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 (kg)</title>
          <units>kg</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="30"/>
                    <count group_id="B2" value="36"/>
                    <count group_id="B3" value="66"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.3" lower_limit="16.6" upper_limit="25.3"/>
                    <measurement group_id="B2" value="20.6" lower_limit="18.3" upper_limit="28.2"/>
                    <measurement group_id="B3" value="20.2" lower_limit="17.5" upper_limit="25.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percentile weight for age</title>
          <units>percentile</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="30"/>
                    <count group_id="B2" value="36"/>
                    <count group_id="B3" value="66"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.0" lower_limit="27.0" upper_limit="86.3"/>
                    <measurement group_id="B2" value="45.0" lower_limit="29.3" upper_limit="84.8"/>
                    <measurement group_id="B3" value="49.5" lower_limit="29.8" upper_limit="85.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Dose of Opioid</title>
        <description>Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.</description>
        <time_frame>Within 24hrs</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Acetaminophen</title>
            <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Acetaminophen</title>
            <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
        </group_list>
        <measure>
          <title>Total Dose of Opioid</title>
          <description>Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.</description>
          <units>mcg/kg</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="30"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="147.6" lower_limit="119.6" upper_limit="193.0"/>
                    <measurement group_id="O2" value="125.4" lower_limit="102.8" upper_limit="150.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.127</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges Lehman estimator</param_type>
            <param_value>21.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.5</ci_lower_limit>
            <ci_upper_limit>44.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Patients With Severe Pain Score of 7 or Higher</title>
        <description>A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.</description>
        <time_frame>24 hrs period following surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Acetaminophen</title>
            <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Acetaminophen</title>
            <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients With Severe Pain Score of 7 or Higher</title>
          <description>A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.</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="30"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.851</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Acetaminophen Level 1 - End of Surgery</title>
        <description>mg/L acetaminophen in the plasma at the end of surgery</description>
        <time_frame>at the end of surgery, about 1 hour after IV Dose</time_frame>
        <population>2 patients in Oral did not have sample obtained for level; 1 patient in IV had value below 10 mg/L limit of quantification</population>
        <group_list>
          <group group_id="O1">
            <title>Oral Acetaminophen</title>
            <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Acetaminophen</title>
            <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Acetaminophen Level 1 - End of Surgery</title>
          <description>mg/L acetaminophen in the plasma at the end of surgery</description>
          <population>2 patients in Oral did not have sample obtained for level; 1 patient in IV had value below 10 mg/L limit of quantification</population>
          <units>mg/L</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="22" lower_limit="16.5" upper_limit="27.8"/>
                    <measurement group_id="O2" value="20" lower_limit="17" upper_limit="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.109</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges Lehman estimator</param_type>
            <param_value>2.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.0</ci_lower_limit>
            <ci_upper_limit>6.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration</title>
        <description>mg/L acetaminophen in the plasma 3 hours after IV study drug administration</description>
        <time_frame>Outcome will be measured 3hrs post first IV Dose</time_frame>
        <population>Acetaminophen plasma levels obtained 3 hours after start of the IV study drug in patients with samples obtained; these were not available for 8 Oral and 9 IV subjects.</population>
        <group_list>
          <group group_id="O1">
            <title>Oral Acetaminophen</title>
            <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Acetaminophen</title>
            <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration</title>
          <description>mg/L acetaminophen in the plasma 3 hours after IV study drug administration</description>
          <population>Acetaminophen plasma levels obtained 3 hours after start of the IV study drug in patients with samples obtained; these were not available for 8 Oral and 9 IV subjects.</population>
          <units>mg/L</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="21"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="15.0" upper_limit="21.0"/>
                    <measurement group_id="O2" value="11" lower_limit="10.3" upper_limit="12.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0001</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Hodges Lehman estimator</param_type>
            <param_value>7.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.0</ci_lower_limit>
            <ci_upper_limit>8.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 hours</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oral Acetaminophen</title>
          <description>Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.&#xD;
Acetaminophen</description>
        </group>
        <group group_id="E2">
          <title>Intravenous Acetaminophen</title>
          <description>Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.&#xD;
Acetaminophen</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="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </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>Richard L. Applegate II MD</name_or_title>
      <organization>UC Davis Anesthesiology &amp; Pain Medicine</organization>
      <phone>916-734-5028</phone>
      <email>rapplegate@ucdavis.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/NCT02994940
org study id: 948256
nct id: NCT02994940
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Acetaminophen is frequently used as an adjunct for pain management in pediatric surgical
      patients. The drug is available in an over the counter, inexpensive oral form as well as a
      considerably more expensive intravenous form. This study will compare opioid requirements and
      acetaminophen plasma levels post operatively for two dosing regimens to compare oral versus
      intravenous routes given pre operatively.
The primary purpose of this study is to compare opioid utilization in post-operative patients
      undergoing tonsillectomy and adenoidectomy, between IV and PO acetaminophen. Secondarily, it
      will provide information regarding possible cost savings, pharmacokinetics and safety between
      these two regimens.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Total Dose of Opioid
time frame: Within 24hrs
description: Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.
measure: Proportion of Patients With Severe Pain Score of 7 or Higher
time frame: 24 hrs period following surgery
description: A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.
measure: Plasma Acetaminophen Level 1 - End of Surgery
time frame: at the end of surgery, about 1 hour after IV Dose
description: mg/L acetaminophen in the plasma at the end of surgery
measure: Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration
time frame: Outcome will be measured 3hrs post first IV Dose
description: mg/L acetaminophen in the plasma 3 hours after IV study drug administration
arm group label: Oral Acetaminophen
arm group type: Experimental
description: Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.
arm group label: Intravenous Acetaminophen
arm group type: Experimental
description: Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.
intervention type: Drug
intervention name: Acetaminophen
description: already included in arm/group descriptions
arm group label: Intravenous Acetaminophen
arm group label: Oral Acetaminophen
other name: OFIRMEV
criteria: 
gender: All
minimum age: 3 Years
maximum age: 17 Years
healthy volunteers: No
last name: Cathy Lammers, MD
role: Principal Investigator
affiliation: UC Davis Children's Hospital
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acetaminophen
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 