<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/NCT03229499</url>
  </required_header>
  <id_info>
    <org_study_id>827486</org_study_id>
    <secondary_id>R01HL134905</secondary_id>
    <nct_id>NCT03229499</nct_id>
  </id_info>
  <brief_title>Pulmonary Hypertension and Anastrozole Trial</brief_title>
  <acronym>PHANTOM</acronym>
  <official_title>Pulmonary Hypertension and Anastrozole Trial (PHANTOM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objectives of this study are to determine whether the study drug, anastrozole may&#xD;
      improve six minute walk distance at six months compared to placebo and to assess safety and&#xD;
      side effects up to twelve months in pulmonary arterial hypertension (PAH).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2017</start_date>
  <completion_date type="Actual">July 22, 2022</completion_date>
  <primary_completion_date type="Actual">July 22, 2022</primary_completion_date>
  <phase>Phase 2</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>Difference in changes in distance walked in six minutes between anastrozole and placebo groups</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in distance walked in six minutes between anastrozole and placebo groups</measure>
    <time_frame>3 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in right ventricular function between anastrozole and placebo groups</measure>
    <time_frame>6 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in plasma NT-proBNP level between anastrozole and placebo groups</measure>
    <time_frame>3 months, 6months,12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in biomarkers between anastrozole and placebo groups</measure>
    <time_frame>3 months, 6months,12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in SF36 between anastrozole and placebo groups</measure>
    <time_frame>3 months, 6months,12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in emPHasis-10 between anastrozole and placebo groups</measure>
    <time_frame>3 months, 6months,12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in actigraphy-measured physical activity between anastrozole and placebo groups</measure>
    <time_frame>3 months, 6months,12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in time-to-clinical worsening (TTCW) between anastrozole and placebo groups</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in changes in bone mineral density between anastrozole and placebo groups</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in side effects between anastrozole and placebo groups at twelve months</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>Anastrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1mg (1 tablet)taken by mouth once a day for one year</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 tablet taken by mouth once a day for one year</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole</intervention_name>
    <description>Anastrozole is an aromatase inhibitor indicated for:&#xD;
adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer&#xD;
first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer&#xD;
treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.</description>
    <arm_group_label>Anastrozole</arm_group_label>
    <other_name>Arimidex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>matching placebo tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previous documentation of mean pulmonary artery pressure &gt; 25 mm Hg with a pulmonary&#xD;
             capillary wedge pressure (or left ventricular end-diastolic pressure) &lt; 16 mm Hg and&#xD;
             PVR &gt; 3 WU at any time before study entry.&#xD;
&#xD;
          -  Diagnosis of PAH which is idiopathic, heritable, drug- or toxin-induced, or associated&#xD;
             with connective tissue disease, congenital heart disease, portal hypertension, or HIV&#xD;
             infection and receiving treatment for PAH.&#xD;
&#xD;
          -  Most recent pulmonary function tests with FEV1/FVC &gt;50% AND either a) total lung&#xD;
             capacity &gt; 70% predicted or b) total lung capacity between 60% and 70% predicted with&#xD;
             no more than mild interstitial lung disease on computerized tomography scan of the&#xD;
             chest.&#xD;
&#xD;
          -  Ability to perform six minute walk testing without significant limitations in&#xD;
             musculoskeletal function or coordination.&#xD;
&#xD;
          -  If female, post-menopausal state, defined as:&#xD;
&#xD;
               -  &gt; 50 years old and a) have not menstruated during the preceding 12 months or b)&#xD;
                  have follicle-stimulating hormone (FSH) levels (&gt; 40 IU/L) or&#xD;
&#xD;
               -  &lt; 50 years and FSH (&gt; 40 IU/L) or&#xD;
&#xD;
               -  having had a bilateral oophorectomy.&#xD;
&#xD;
          -  Informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18.&#xD;
&#xD;
          -  Current treatment with estrogen, hormone therapy, or anti-hormone therapy (tamoxifen,&#xD;
             fulvestrant, etc.)&#xD;
&#xD;
          -  WHO Class IV functional status.&#xD;
&#xD;
          -  History of invasive breast cancer.&#xD;
&#xD;
          -  Clinically significant untreated sleep apnea.&#xD;
&#xD;
          -  Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency&#xD;
             or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection&#xD;
             fraction &lt; 45% on most recent echocardiography (within 1 year).&#xD;
&#xD;
          -  Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists,&#xD;
             phosphodiesterase-5 inhibitors, riociguat, selexipag) within three months of&#xD;
             enrollment; the dose must be stable for at least three months prior to Baseline Visit.&#xD;
             PAH therapy which is stopped and then restarted or has dose changes which are not&#xD;
             related to initiation and uptitration will be allowed within 3 months prior to the&#xD;
             Baseline Visit.&#xD;
&#xD;
          -  Hospitalized or acutely ill.&#xD;
&#xD;
          -  Renal failure (creatinine ≥ 2.0).&#xD;
&#xD;
          -  Hypercalcemia.&#xD;
&#xD;
          -  Severe osteoporosis: T score -2.5 to -3.4 without bone modifying treatment OR T score&#xD;
             = - 3.5 or lower&#xD;
&#xD;
          -  Child-Pugh Class C cirrhosis.&#xD;
&#xD;
          -  Current or recent (&lt; 3 months) chronic heavy alcohol consumption.&#xD;
&#xD;
          -  Enrollment in a clinical trial or concurrent use of another investigational drug or&#xD;
             device within 30 days of screening visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven M Kawut, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado - Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>East Providence</city>
        <state>Rhode Island</state>
        <zip>02914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 18, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <disposition_first_submitted>June 28, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>August 9, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 31, 2023</disposition_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Randomized Controlled Trial</keyword>
  <keyword>clinical trial</keyword>
  <keyword>anastrozole</keyword>
  <keyword>pulmonary hypertension</keyword>
  <keyword>pulmonary arterial hypertension</keyword>
  <keyword>PAH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anastrozole</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03229499
org study id: 827486
secondary id: R01HL134905
nct id: NCT03229499
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The primary objectives of this study are to determine whether the study drug, anastrozole may
      improve six minute walk distance at six months compared to placebo and to assess safety and
      side effects up to twelve months in pulmonary arterial hypertension (PAH).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Difference in changes in distance walked in six minutes between anastrozole and placebo groups
time frame: 6 months
measure: Difference in changes in distance walked in six minutes between anastrozole and placebo groups
time frame: 3 months, 12 months
measure: Difference in right ventricular function between anastrozole and placebo groups
time frame: 6 months, 12 months
measure: Difference in changes in plasma NT-proBNP level between anastrozole and placebo groups
time frame: 3 months, 6months,12 months
measure: Difference in changes in biomarkers between anastrozole and placebo groups
time frame: 3 months, 6months,12 months
measure: Difference in changes in SF36 between anastrozole and placebo groups
time frame: 3 months, 6months,12 months
measure: Difference in changes in emPHasis-10 between anastrozole and placebo groups
time frame: 3 months, 6months,12 months
measure: Difference in changes in actigraphy-measured physical activity between anastrozole and placebo groups
time frame: 3 months, 6months,12 months
measure: Difference in time-to-clinical worsening (TTCW) between anastrozole and placebo groups
time frame: 12 months
measure: Difference in changes in bone mineral density between anastrozole and placebo groups
time frame: 12 months
measure: Difference in side effects between anastrozole and placebo groups at twelve months
time frame: 12 months
arm group label: Anastrozole
arm group type: Experimental
description: 1mg (1 tablet)taken by mouth once a day for one year
arm group label: Placebo
arm group type: Placebo Comparator
description: 1 tablet taken by mouth once a day for one year
intervention type: Drug
intervention name: Anastrozole
description: Anastrozole is an aromatase inhibitor indicated for:
adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer
first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer
treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.
arm group label: Anastrozole
other name: Arimidex
intervention type: Drug
intervention name: Placebo Oral Tablet
description: matching placebo tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven M Kawut, MD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Pulmonary Arterial Hypertension
mesh term: Hypertension
mesh term: Anastrozole