<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/NCT02189668</url>
  </required_header>
  <id_info>
    <org_study_id>IRB14-00218</org_study_id>
    <nct_id>NCT02189668</nct_id>
  </id_info>
  <brief_title>Non-operative Management of Pediatric Appendicitis With an Appendicoltih</brief_title>
  <official_title>Non-operative Management of Uncomplicated Appendicitis With an Appendicolth in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter Minneci</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nationwide Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine if non-operative management with antibiotics alone is a feasible treatment&#xD;
      alternative for pediatric patients with uncomplicated acute appendicitis with an&#xD;
      appendicolith identified on imaging.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a prospective randomized clinical trial comparing non-operative management with&#xD;
      antibiotics to urgent appendectomy in children (ages 7-17yrs) with acute appendicitis with&#xD;
      the presence of an appendicolith. Enrolled participants were followed up to 1 year&#xD;
      post-discharge to observe the rates of appendicitis recurrence as well as identify the number&#xD;
      of patients with complicated appendicitis as determined by pathologic examination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    High failure rate&#xD;
  </why_stopped>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants That Did Not Have an Appendectomy</measure>
    <time_frame>1 year</time_frame>
    <description>Percentage of patients who were successfully managed nonoperatively with success defined as not undergoing appendectomy by one year after discharge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Complicated Appendicitis</measure>
    <time_frame>1 year</time_frame>
    <description>Percent of patients found to have complicated appendicitis (gangrenous or perforated) on pathologic examination.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Appendicitis</condition>
  <arm_group>
    <arm_group_label>Non-operative Management</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-operative management with antibiotics only Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surgery</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Usual care with urgent appendectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antibiotics only (Zosyn then Augmentin)</intervention_name>
    <description>Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic</description>
    <arm_group_label>Non-operative Management</arm_group_label>
    <other_name>non operative management</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age : 7-17 years&#xD;
&#xD;
          -  Abdominal pain &lt;/= 48hours prior to receiving antibiotics&#xD;
&#xD;
          -  White Blood Cell Count &gt;5 but &lt; 18&#xD;
&#xD;
          -  US or CT confirmed early appendicitis plus:&#xD;
&#xD;
               -  US: &lt;/=1.1 cm in diameter, presence of appendicolith&#xD;
&#xD;
               -  CT: &lt;/= 1.1cm in diameter, presence of appendicolith&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive urine pregnancy test&#xD;
&#xD;
          -  Pain &gt; 48 hours prior to first antibiotic dose&#xD;
&#xD;
          -  Diffuse peritonitis&#xD;
&#xD;
          -  History of chronic intermittent abdominal pain&#xD;
&#xD;
          -  White Blood Cell count ≤ 5 or ≥ 18&#xD;
&#xD;
          -  Absence of appendicolith or any evidence on imaging studies concerning for evolving&#xD;
             perforated appendicitis including abscess or phlegmon&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter C Minneci, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Minneci PC, Sulkowski JP, Nacion KM, Mahida JB, Cooper JN, Moss RL, Deans KJ. Feasibility of a nonoperative management strategy for uncomplicated acute appendicitis in children. J Am Coll Surg. 2014 Aug;219(2):272-9. doi: 10.1016/j.jamcollsurg.2014.02.031. Epub 2014 Apr 13.</citation>
    <PMID>24951281</PMID>
  </reference>
  <results_reference>
    <citation>Mahida JB, Lodwick DL, Nacion KM, Sulkowski JP, Leonhart KL, Cooper JN, Ambeba EJ, Deans KJ, Minneci PC. High failure rate of nonoperative management of acute appendicitis with an appendicolith in children. J Pediatr Surg. 2016 Jun;51(6):908-11. doi: 10.1016/j.jpedsurg.2016.02.056. Epub 2016 Mar 2.</citation>
    <PMID>27018085</PMID>
  </results_reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <results_first_submitted>March 15, 2018</results_first_submitted>
  <results_first_submitted_qc>March 15, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">April 17, 2018</results_first_posted>
  <last_update_submitted>October 28, 2018</last_update_submitted>
  <last_update_submitted_qc>October 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>Peter Minneci</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Appendicitis</keyword>
  <keyword>Non-operative</keyword>
  <keyword>Children</keyword>
  <keyword>Appendicolith</keyword>
  <keyword>fecalith</keyword>
  <keyword>Pediatrics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Appendicitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Amoxicillin-Potassium Clavulanate Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Non-operative</title>
          <description>Non-operative management with antibiotics alone Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic&#xD;
Antibiotics only (Zosyn then Augmentin): Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic</description>
        </group>
        <group group_id="P2">
          <title>Surgery</title>
          <description>Usual care with urgent appendectomy</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Non-operative</title>
          <description>Non-operative management with antibiotics alone Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic&#xD;
Antibiotics only (Zosyn then Augmentin): Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic</description>
        </group>
        <group group_id="B2">
          <title>Surgery</title>
          <description>Usual care with urgent appendectomy</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="5"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="14"/>
          </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14" lower_limit="13" upper_limit="14"/>
                    <measurement group_id="B2" value="11" lower_limit="9" upper_limit="15"/>
                    <measurement group_id="B3" value="12" lower_limit="11" upper_limit="14"/>
                  </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="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants That Did Not Have an Appendectomy</title>
        <description>Percentage of patients who were successfully managed nonoperatively with success defined as not undergoing appendectomy by one year after discharge</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-operative</title>
            <description>Non-operative management with antibiotics alone Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic&#xD;
Antibiotics only (Zosyn then Augmentin): Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic</description>
          </group>
          <group group_id="O2">
            <title>Surgery</title>
            <description>Usual care with urgent appendectomy</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants That Did Not Have an Appendectomy</title>
          <description>Percentage of patients who were successfully managed nonoperatively with success defined as not undergoing appendectomy by one year after discharge</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="5"/>
                <count group_id="O2" value="9"/>
              </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>Number of Participants With Complicated Appendicitis</title>
        <description>Percent of patients found to have complicated appendicitis (gangrenous or perforated) on pathologic examination.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-operative</title>
            <description>Non-operative management with antibiotics alone Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic&#xD;
Antibiotics only (Zosyn then Augmentin): Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic</description>
          </group>
          <group group_id="O2">
            <title>Surgery</title>
            <description>Usual care with urgent appendectomy</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complicated Appendicitis</title>
          <description>Percent of patients found to have complicated appendicitis (gangrenous or perforated) on pathologic examination.</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="5"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events data were collected for the duration of the follow-ups which was up to 1 year post-discharge.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Non-operative</title>
          <description>Non-operative management with antibiotics alone Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic&#xD;
Antibiotics only (Zosyn then Augmentin): Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic</description>
        </group>
        <group group_id="E2">
          <title>Surgery</title>
          <description>Usual care with urgent appendectomy</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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </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>Peter Minneci</name_or_title>
      <organization>Nationwide Children's Hospital</organization>
      <phone>6147223066</phone>
      <email>peter.minneci@nationwidechildrens.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02189668
org study id: IRB14-00218
nct id: NCT02189668
lead sponsor: 
has dmc: No
To determine if non-operative management with antibiotics alone is a feasible treatment
      alternative for pediatric patients with uncomplicated acute appendicitis with an
      appendicolith identified on imaging.
This study is a prospective randomized clinical trial comparing non-operative management with
      antibiotics to urgent appendectomy in children (ages 7-17yrs) with acute appendicitis with
      the presence of an appendicolith. Enrolled participants were followed up to 1 year
      post-discharge to observe the rates of appendicitis recurrence as well as identify the number
      of patients with complicated appendicitis as determined by pathologic examination.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants That Did Not Have an Appendectomy
time frame: 1 year
description: Percentage of patients who were successfully managed nonoperatively with success defined as not undergoing appendectomy by one year after discharge
measure: Number of Participants With Complicated Appendicitis
time frame: 1 year
description: Percent of patients found to have complicated appendicitis (gangrenous or perforated) on pathologic examination.
arm group label: Non-operative Management
arm group type: Experimental
description: Non-operative management with antibiotics only Zosyn (Piperacillin/Tazobactam) and then Augmentin unless penicillin allergic Cipro/Flagyl if penicillin allergic
arm group label: Surgery
arm group type: No Intervention
description: Usual care with urgent appendectomy
intervention type: Drug
intervention name: Antibiotics only (Zosyn then Augmentin)
description: Intravenous and oral antibiotics without surgery Piperacillin/Tazobactam and then Augmentin Cipro/Flagyl if Penicillin allergic
arm group label: Non-operative Management
other name: non operative management
criteria: 
gender: All
minimum age: 7 Years
maximum age: 17 Years
healthy volunteers: No
last name: Peter C Minneci, MD
role: Principal Investigator
affiliation: Nationwide Children's Hospital
facility: 
country: United States
citation: Minneci PC, Sulkowski JP, Nacion KM, Mahida JB, Cooper JN, Moss RL, Deans KJ. Feasibility of a nonoperative management strategy for uncomplicated acute appendicitis in children. J Am Coll Surg. 2014 Aug;219(2):272-9. doi: 10.1016/j.jamcollsurg.2014.02.031. Epub 2014 Apr 13.
PMID: 24951281
citation: Mahida JB, Lodwick DL, Nacion KM, Sulkowski JP, Leonhart KL, Cooper JN, Ambeba EJ, Deans KJ, Minneci PC. High failure rate of nonoperative management of acute appendicitis with an appendicolith in children. J Pediatr Surg. 2016 Jun;51(6):908-11. doi: 10.1016/j.jpedsurg.2016.02.056. Epub 2016 Mar 2.
PMID: 27018085
responsible party type: Sponsor-Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: Peter Minneci
investigator title: Principal Investigator
mesh term: Appendicitis
mesh term: Anti-Bacterial Agents
mesh term: Amoxicillin-Potassium Clavulanate Combination
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 