<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/NCT01721564</url>
  </required_header>
  <id_info>
    <org_study_id>X05-0255</org_study_id>
    <nct_id>NCT01721564</nct_id>
  </id_info>
  <brief_title>Bosentan and Pulmonary Endothelial Function</brief_title>
  <acronym>PARBO</acronym>
  <official_title>Pulmonary Artery Remodelling With Bosentan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prof David S Celermajer</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal Prince Alfred Hospital, Sydney, Australia</source>
  <brief_summary>
    <textblock>
      6 months therapy of Bosentan, an endothelin antagonist, will lead to improvement in pulmonary&#xD;
      microvascular endothelial function.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2006</start_date>
  <completion_date type="Actual">December 2009</completion_date>
  <primary_completion_date type="Actual">May 2009</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acetylcholine Vascular Reactivity Response</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>Percent pulmonary flow change from baseline after acetylcholine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intravascular Ultrasound - Pulmonary Artery Wall Thickness</measure>
    <time_frame>baseline and 6 months</time_frame>
    <description>Change in intima-media thickness</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>Bosentan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bosentan</intervention_name>
    <description>62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months</description>
    <arm_group_label>Bosentan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pulmonary arterial hypertension; idiopathic and connective tissue disease associated&#xD;
&#xD;
          -  Confirmed or invasive haemodynamic:&#xD;
&#xD;
          -  Mean pulmonary arterial pressure greater than or equal to 25 millimeters of mercury&#xD;
&#xD;
          -  Pulmonary capillary wedge pressure less than 15 millimeters of mercury&#xD;
&#xD;
          -  No prior pulmonary hypertension specific therapy&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contra-indications to medications used to test endothelial function; acetylcholine,&#xD;
             sodium nitroprusside, NG-Monomethyl-L-Arginine, L-arginine&#xD;
&#xD;
          -  Advanced renal disease&#xD;
&#xD;
          -  Previous allergic reaction to contrast agents&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David S Celermajer, MBBS, PhD, DSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Prince Alfred Hospital, Sydney, Australia</affiliation>
  </overall_official>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <results_first_submitted>December 4, 2012</results_first_submitted>
  <results_first_submitted_qc>January 21, 2013</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 25, 2013</results_first_posted>
  <last_update_submitted>October 18, 2016</last_update_submitted>
  <last_update_submitted_qc>October 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Royal Prince Alfred Hospital, Sydney, Australia</investigator_affiliation>
    <investigator_full_name>Prof David S Celermajer</investigator_full_name>
    <investigator_title>Scandrett Professor of Cardiology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bosentan</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bosentan</title>
          <description>62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bosentan</title>
          <description>62.5 mg Bosentan b.i.d. for 1 month 125 mg Bosentan b.i.d. for 5 months</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" spread="4"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Acetylcholine Vascular Reactivity Response</title>
        <description>Percent pulmonary flow change from baseline after acetylcholine</description>
        <time_frame>Baseline and 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bosentan</title>
            <description>62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months</description>
          </group>
        </group_list>
        <measure>
          <title>Acetylcholine Vascular Reactivity Response</title>
          <description>Percent pulmonary flow change from baseline after acetylcholine</description>
          <units>percentage of baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="180" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intravascular Ultrasound - Pulmonary Artery Wall Thickness</title>
        <description>Change in intima-media thickness</description>
        <time_frame>baseline and 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bosentan</title>
            <description>62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months</description>
          </group>
        </group_list>
        <measure>
          <title>Intravascular Ultrasound - Pulmonary Artery Wall Thickness</title>
          <description>Change in intima-media thickness</description>
          <units>percentage of baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Bosentan</title>
          <description>62.5 mg Bosentan b.i.d. for 1 month 125 mg Bosentan b.i.d. for 5 months</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
              </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>Prof David Celermajer</name_or_title>
      <organization>Royal Prince Alfred Hospital, Sydney, Australia</organization>
      <phone>+61 2 9515 6519</phone>
      <email>david.celermajer@email.cs.nsw.gov.au</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/NCT01721564
org study id: X05-0255
nct id: NCT01721564
lead sponsor: 
6 months therapy of Bosentan, an endothelin antagonist, will lead to improvement in pulmonary
      microvascular endothelial function.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Acetylcholine Vascular Reactivity Response
time frame: Baseline and 6 months
description: Percent pulmonary flow change from baseline after acetylcholine
measure: Intravascular Ultrasound - Pulmonary Artery Wall Thickness
time frame: baseline and 6 months
description: Change in intima-media thickness
arm group label: Bosentan
arm group type: Experimental
description: 62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months
intervention type: Drug
intervention name: Bosentan
description: 62.5 mg Bosentan twice a day for 1 month 125 mg Bosentan twice a day for 5 months
arm group label: Bosentan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: David S Celermajer, MBBS, PhD, DSc
role: Principal Investigator
affiliation: Royal Prince Alfred Hospital, Sydney, Australia
responsible party type: Sponsor-Investigator
investigator affiliation: Royal Prince Alfred Hospital, Sydney, Australia
investigator full name: Prof David S Celermajer
investigator title: Scandrett Professor of Cardiology
mesh term: Pulmonary Arterial Hypertension
mesh term: Bosentan
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 