<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/NCT01717742</url>
  </required_header>
  <id_info>
    <org_study_id>1000033767</org_study_id>
    <nct_id>NCT01717742</nct_id>
  </id_info>
  <brief_title>Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)</brief_title>
  <official_title>Intrapleural DNase and Tissue Plasminogen Activator in Pediatric Empyema (DTPA Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital of Eastern Ontario</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Justine's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Physicians' Services Incorporated Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McMaster Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>British Columbia Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Hospital for Sick Children</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bacterial pneumonia can be complicated by the development of excess fluid and pus (pleural&#xD;
      empyema) around the lungs in children. The incidence of pleural empyema in children has&#xD;
      increased significantly in the last 10 years.&#xD;
&#xD;
      Short term morbidity for this condition is substantial, but unlike in adults, the long term&#xD;
      outcome of this condition for children in developed countries is favourable. Inserting a&#xD;
      chest drain and then adding a medicine (tissue plasminogen activator - tPA) to break down&#xD;
      organized pus has been shown to be an effective therapy for reducing the duration of illness.&#xD;
      However, this treatment is still suboptimal and prolonged hospitalization is common. Recent&#xD;
      data from adults suggests that adding an additional medicine (DNase) to decrease the&#xD;
      viscosity (thickness) of the fluid improves drainage and leads to better patient outcomes;&#xD;
      however, there are no published studies on children.&#xD;
&#xD;
      This is a multi-centre randomized controlled trial comparing the time to discharge from&#xD;
      hospital after chest drain insertion in previously well children who present with pleural&#xD;
      empyema, treated with intrapleural DNase and tissue plasminogen activator (tPA) by chest&#xD;
      drain for three doses over 48 hours compared with three doses over 48 hours of tPA alone.&#xD;
      Other outcomes related to effectiveness, safety and cost will be assessed as well.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Hospital Discharge</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Time from insertion of the chest drain to discharge from hospital.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Meeting Discharge Criteria</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Time from insertion of the chest drain to meeting discharge criteria.&#xD;
Discharge criteria:&#xD;
Chest tube removed&#xD;
No fever [temperature less than 38°C]&#xD;
Normal respiratory rate forage&#xD;
No hypoxia&#xD;
Drinking fluids wel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Drain Removal</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Time from drain insertion to drain removal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Fever After Intervention</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Duration of fever (defined as temperature &gt;38 degrees celsius taken by any method) from insertion of the chest drain until resolution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Serious Bleeding</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Further Interventions</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Number of participants who needed further intervention such as placement of another chest drain (by any technique) or surgical intervention such as thoracotomy and decortication, video-assisted thorascopic surgery, or pneumonectomy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Hospital Readmission</measure>
    <time_frame>3 months post-discharge</time_frame>
    <description>Number of Participants who had any hospital readmission after discharge from hospital for initial treatment for pleural empyema within three months related to pleural empyema or its treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost of the Hospitalization</measure>
    <time_frame>up to 4 months</time_frame>
    <description>An economic evaluation will compare the relative costs of DNase-tPA with tPA alone in previously well children who present with pleural empyema, using patient-level data from the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>up to 4 months</time_frame>
    <description>Mortality from any cause during the hospitalization for empyema.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Chest Radiography</measure>
    <time_frame>7 days after drain removal</time_frame>
    <description>The radiograph closest to the time of drain removal will be reviewed by a blinded study radiologist to determine the percentage of hemithorax occupied using a 5 point ordinal scale utilized in previous studies ranging from no fluid present to fluid occupying &gt;75% of the most affected hemithorax.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">97</enrollment>
  <condition>Pleural Empyema</condition>
  <arm_group>
    <arm_group_label>tPA and placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>tPA and DNase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPA (Tissue Plasminogen Activator)</intervention_name>
    <description>Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (&gt;10 kg) normal saline once daily for 3 days</description>
    <arm_group_label>tPA and DNase</arm_group_label>
    <arm_group_label>tPA and placebo</arm_group_label>
    <other_name>Cathflo (alteplase, recombinant)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DNase</intervention_name>
    <description>Intrapleural administration of DNase 5 mg diluted to 10 ml (≤10 kg) or 20 ml (&gt;10 kg) normal saline once daily for 3 days</description>
    <arm_group_label>tPA and DNase</arm_group_label>
    <other_name>Pulmozyme (Dornase alfa)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (&gt;10 kg)</description>
    <arm_group_label>tPA and placebo</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age 6 months to 18 years&#xD;
&#xD;
          2. hospitalized with diagnosis of pleural empyema requiring chest tube drainage with&#xD;
             fibrinolytics as judged by the attending physician with the following criteria:&#xD;
&#xD;
               1. pneumonia with pleural effusion as documented on ultrasound of the chest; AND&#xD;
&#xD;
               2. need for further intervention in addition to antibiotics based on clinical&#xD;
                  criteria [persistent fever despite on antibiotics for at least 48 hours OR&#xD;
                  significant respiratory distress tachypnea, hypoxia) as a result of the pleural&#xD;
                  fluid collection]&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. empyema as a result of tuberculosis, fungus or non-infectious causes (e.g. malignancy)&#xD;
&#xD;
          2. known coagulation impairment&#xD;
&#xD;
          3. suspected or proven allergy to tPA or DNase&#xD;
&#xD;
          4. chronic lung disease or other chronic illnesses (e.g. immunodeficiency or neurologic&#xD;
             impairment)&#xD;
&#xD;
          5. child has already undergone a drainage procedure (e.g. chest drain or VATS).&#xD;
&#xD;
          6. recent administration of an investigational drug (within previous 30 days)&#xD;
&#xD;
          7. pregnancy&#xD;
&#xD;
          8. breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eyal Cohen, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Hospital for Sick Children</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alberta Children's Hospital</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>British Columbia Children's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>BC V6H 3N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McMaster Children's Hospital</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Eastern Ontario</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital for Sick Children(SickKids)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Sainte Justine</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <results_reference>
    <citation>Livingston MH, Mahant S, Connolly B, MacLusky I, Laberge S, Giglia L, Yang C, Roberts A, Shawyer A, Brindle M, Parsons S, Stoian C, Walton JM, Thorpe KE, Chen Y, Zuo F, Mamdani M, Chan C, Loong D, Isaranuwatchai W, Ratjen F, Cohen E. Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema: A Randomized Clinical Trial. JAMA Pediatr. 2020 Apr 1;174(4):332-340. doi: 10.1001/jamapediatrics.2019.5863.</citation>
    <PMID>32011642</PMID>
  </results_reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <results_first_submitted>March 16, 2020</results_first_submitted>
  <results_first_submitted_qc>March 23, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 3, 2020</results_first_posted>
  <last_update_submitted>April 6, 2020</last_update_submitted>
  <last_update_submitted_qc>April 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Eyal Cohen</investigator_full_name>
    <investigator_title>Staff Physician</investigator_title>
  </responsible_party>
  <keyword>Randomized controlled trial</keyword>
  <keyword>Pleural Empyema</keyword>
  <keyword>tPA</keyword>
  <keyword>DNase</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Empyema</mesh_term>
    <mesh_term>Empyema, Pleural</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tissue Plasminogen Activator</mesh_term>
    <mesh_term>Plasminogen</mesh_term>
  </intervention_browse>
  <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 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT01717742/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>October 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT01717742/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>tPA (Tissue Plasminogen Activator) and Placebo</title>
          <description>tPA: Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (&gt;10 kg) normal saline once daily for 3 days&#xD;
Placebo: Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (&gt;10 kg)</description>
        </group>
        <group group_id="P2">
          <title>tPA (Tissue Plasminogen Activator) and DNase</title>
          <description>tPA: Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (&gt;10 kg) normal saline once daily for 3 days&#xD;
DNase: Intrapleural administration of DNase 5 mg diluted to 10 ml (≤10 kg) or 20 ml (&gt;10 kg) normal saline once daily for 3 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="49"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intervention (tPA &amp; DNase)</title>
          <description>Intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
        </group>
        <group group_id="B2">
          <title>Placebo (tPA &amp; Placebo)</title>
          <description>Intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</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="49"/>
            <count group_id="B2" value="48"/>
            <count group_id="B3" value="97"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.4" spread="43.3"/>
                    <measurement group_id="B2" value="64.1" spread="44.2"/>
                    <measurement group_id="B3" value="61.3" spread="45.6"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/ethnicity</title>
              <category_list>
                <category>
                  <title>First nations</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>African</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian/Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Middle Eastern</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>South Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Prefer not to answer</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to Hospital Discharge</title>
        <description>Time from insertion of the chest drain to discharge from hospital.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Hospital Discharge</title>
          <description>Time from insertion of the chest drain to discharge from hospital.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" spread="4.9"/>
                    <measurement group_id="O2" value="9.1" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Meeting Discharge Criteria</title>
        <description>Time from insertion of the chest drain to meeting discharge criteria.&#xD;
Discharge criteria:&#xD;
Chest tube removed&#xD;
No fever [temperature less than 38°C]&#xD;
Normal respiratory rate forage&#xD;
No hypoxia&#xD;
Drinking fluids wel</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Meeting Discharge Criteria</title>
          <description>Time from insertion of the chest drain to meeting discharge criteria.&#xD;
Discharge criteria:&#xD;
Chest tube removed&#xD;
No fever [temperature less than 38°C]&#xD;
Normal respiratory rate forage&#xD;
No hypoxia&#xD;
Drinking fluids wel</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.2" spread="4.5"/>
                    <measurement group_id="O2" value="8.5" spread="5.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Drain Removal</title>
        <description>Time from drain insertion to drain removal.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Drain Removal</title>
          <description>Time from drain insertion to drain removal.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" spread="4.3"/>
                    <measurement group_id="O2" value="6.9" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Fever After Intervention</title>
        <description>Duration of fever (defined as temperature &gt;38 degrees celsius taken by any method) from insertion of the chest drain until resolution.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Fever After Intervention</title>
          <description>Duration of fever (defined as temperature &gt;38 degrees celsius taken by any method) from insertion of the chest drain until resolution.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="3.4"/>
                    <measurement group_id="O2" value="3.3" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention</title>
        <description>Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention</title>
          <description>Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.</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="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Serious Bleeding</title>
        <description>Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious Bleeding</title>
          <description>Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.</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="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Further Interventions</title>
        <description>Number of participants who needed further intervention such as placement of another chest drain (by any technique) or surgical intervention such as thoracotomy and decortication, video-assisted thorascopic surgery, or pneumonectomy.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Further Interventions</title>
          <description>Number of participants who needed further intervention such as placement of another chest drain (by any technique) or surgical intervention such as thoracotomy and decortication, video-assisted thorascopic surgery, or pneumonectomy.</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="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Hospital Readmission</title>
        <description>Number of Participants who had any hospital readmission after discharge from hospital for initial treatment for pleural empyema within three months related to pleural empyema or its treatment.</description>
        <time_frame>3 months post-discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Hospital Readmission</title>
          <description>Number of Participants who had any hospital readmission after discharge from hospital for initial treatment for pleural empyema within three months related to pleural empyema or its treatment.</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="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cost of the Hospitalization</title>
        <description>An economic evaluation will compare the relative costs of DNase-tPA with tPA alone in previously well children who present with pleural empyema, using patient-level data from the trial.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Cost of the Hospitalization</title>
          <description>An economic evaluation will compare the relative costs of DNase-tPA with tPA alone in previously well children who present with pleural empyema, using patient-level data from the trial.</description>
          <units>2018 US $</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11329" spread="7139"/>
                    <measurement group_id="O2" value="10760" spread="5071"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mortality</title>
        <description>Mortality from any cause during the hospitalization for empyema.</description>
        <time_frame>up to 4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Mortality</title>
          <description>Mortality from any cause during the hospitalization for empyema.</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="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Chest Radiography</title>
        <description>The radiograph closest to the time of drain removal will be reviewed by a blinded study radiologist to determine the percentage of hemithorax occupied using a 5 point ordinal scale utilized in previous studies ranging from no fluid present to fluid occupying &gt;75% of the most affected hemithorax.</description>
        <time_frame>7 days after drain removal</time_frame>
        <population>Degree of opacification on chest radiography prior to chest tube removal</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Intervention group received intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
          </group>
        </group_list>
        <measure>
          <title>Chest Radiography</title>
          <description>The radiograph closest to the time of drain removal will be reviewed by a blinded study radiologist to determine the percentage of hemithorax occupied using a 5 point ordinal scale utilized in previous studies ranging from no fluid present to fluid occupying &gt;75% of the most affected hemithorax.</description>
          <population>Degree of opacification on chest radiography prior to chest tube removal</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=25%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>26-50%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>51-75%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;75%</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Over the course of the patient's hospitalization</time_frame>
      <desc>All serious unexpected adverse events were reported to the REB. All serious adverse drug reactions to the study medication were reported to Health Canada within 15 calendar days or for death or life-threatening events, within 7 calendar days. In the latter case, a follow-up report was filed within 8 calendar days. Adverse reactions will be managed according to the standard clinical management practices. All adverse events and adverse reactions were reported to the PI within 24 hours.</desc>
      <group_list>
        <group group_id="E1">
          <title>Intervention</title>
          <description>Intervention group received ) intrapleural tPA, 4 mg, followed by DNase (Roche), 5 mg</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Control group received intrapleural tPA (Roche), 4 mg, followed by 5 mL of normal saline</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="49"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Serious bleeding</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Low hemoglobin levels</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>TENSION PYOTHORAX</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Bronchopleural fistula</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Hemothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="49"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Mild bleeding</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Transient chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Low albumin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Elevated potassium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Chest tube removed accidentally</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Herpes simplex virus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Other bacterial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Kinked chest tube</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="48"/>
              </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>Dr. Eyal cohen</name_or_title>
      <organization>Hospital for Sick Children</organization>
      <phone>416-813-7654</phone>
      <email>eyal.cohen@sickkids.ca</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/NCT01717742
org study id: 1000033767
nct id: NCT01717742
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Bacterial pneumonia can be complicated by the development of excess fluid and pus (pleural
      empyema) around the lungs in children. The incidence of pleural empyema in children has
      increased significantly in the last 10 years.

      Short term morbidity for this condition is substantial, but unlike in adults, the long term
      outcome of this condition for children in developed countries is favourable. Inserting a
      chest drain and then adding a medicine (tissue plasminogen activator - tPA) to break down
      organized pus has been shown to be an effective therapy for reducing the duration of illness.
      However, this treatment is still suboptimal and prolonged hospitalization is common. Recent
      data from adults suggests that adding an additional medicine (DNase) to decrease the
      viscosity (thickness) of the fluid improves drainage and leads to better patient outcomes;
      however, there are no published studies on children.

      This is a multi-centre randomized controlled trial comparing the time to discharge from
      hospital after chest drain insertion in previously well children who present with pleural
      empyema, treated with intrapleural DNase and tissue plasminogen activator (tPA) by chest
      drain for three doses over 48 hours compared with three doses over 48 hours of tPA alone.
      Other outcomes related to effectiveness, safety and cost will be assessed as well.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to Hospital Discharge
time frame: up to 4 months
description: Time from insertion of the chest drain to discharge from hospital.
measure: Time to Meeting Discharge Criteria
time frame: up to 4 months
description: Time from insertion of the chest drain to meeting discharge criteria.
Discharge criteria:
Chest tube removed
No fever [temperature less than 38°C]
Normal respiratory rate forage
No hypoxia
Drinking fluids wel
measure: Time to Drain Removal
time frame: up to 4 months
description: Time from drain insertion to drain removal.
measure: Duration of Fever After Intervention
time frame: up to 4 months
description: Duration of fever (defined as temperature >38 degrees celsius taken by any method) from insertion of the chest drain until resolution.
measure: Number of Participants With Need for Ventilatory Support or Non-invasive Ventilation Following the Intervention
time frame: up to 4 months
description: Number of Participants with need for any kind of ventilatory support or any kind of non-invasive ventilation right after the intervention.
measure: Number of Participants With Serious Bleeding
time frame: up to 4 months
description: Number of Participants who had intrapleural bleeding resulting in a drop in hemoglobin of greater than 20 g/L or needing a transfusion.
measure: Number of Participants With Further Interventions
time frame: up to 4 months
description: Number of participants who needed further intervention such as placement of another chest drain (by any technique) or surgical intervention such as thoracotomy and decortication, video-assisted thorascopic surgery, or pneumonectomy.
measure: Number of Participants With Hospital Readmission
time frame: 3 months post-discharge
description: Number of Participants who had any hospital readmission after discharge from hospital for initial treatment for pleural empyema within three months related to pleural empyema or its treatment.
measure: Cost of the Hospitalization
time frame: up to 4 months
description: An economic evaluation will compare the relative costs of DNase-tPA with tPA alone in previously well children who present with pleural empyema, using patient-level data from the trial.
measure: Mortality
time frame: up to 4 months
description: Mortality from any cause during the hospitalization for empyema.
measure: Chest Radiography
time frame: 7 days after drain removal
description: The radiograph closest to the time of drain removal will be reviewed by a blinded study radiologist to determine the percentage of hemithorax occupied using a 5 point ordinal scale utilized in previous studies ranging from no fluid present to fluid occupying >75% of the most affected hemithorax.
arm group label: tPA and placebo
arm group type: Active Comparator
arm group label: tPA and DNase
arm group type: Experimental
intervention type: Drug
intervention name: TPA (Tissue Plasminogen Activator)
description: Intrapleural administration of tPA 4 mg in 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days
arm group label: tPA and DNase
arm group label: tPA and placebo
other name: Cathflo (alteplase, recombinant)
intervention type: Drug
intervention name: DNase
description: Intrapleural administration of DNase 5 mg diluted to 10 ml (≤10 kg) or 20 ml (>10 kg) normal saline once daily for 3 days
arm group label: tPA and DNase
other name: Pulmozyme (Dornase alfa)
intervention type: Other
intervention name: Placebo
description: Intrapleural administration of normal saline 10 ml (≤10 kg) or 20 ml (>10 kg)
arm group label: tPA and placebo
other name: Normal saline
criteria: 
gender: All
minimum age: 6 Months
maximum age: 18 Years
healthy volunteers: No
last name: Eyal Cohen, MD, MSc
role: Principal Investigator
affiliation: The Hospital for Sick Children
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
citation: Livingston MH, Mahant S, Connolly B, MacLusky I, Laberge S, Giglia L, Yang C, Roberts A, Shawyer A, Brindle M, Parsons S, Stoian C, Walton JM, Thorpe KE, Chen Y, Zuo F, Mamdani M, Chan C, Loong D, Isaranuwatchai W, Ratjen F, Cohen E. Effectiveness of Intrapleural Tissue Plasminogen Activator and Dornase Alfa vs Tissue Plasminogen Activator Alone in Children with Pleural Empyema: A Randomized Clinical Trial. JAMA Pediatr. 2020 Apr 1;174(4):332-340. doi: 10.1001/jamapediatrics.2019.5863.
PMID: 32011642
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Eyal Cohen
investigator title: Staff Physician
mesh term: Empyema
mesh term: Empyema, Pleural
mesh term: Tissue Plasminogen Activator
mesh term: Plasminogen
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 