<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/NCT03267108</url>
  </required_header>
  <id_info>
    <org_study_id>PULSE-PHPF-001</org_study_id>
    <nct_id>NCT03267108</nct_id>
  </id_info>
  <brief_title>A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension</brief_title>
  <acronym>REBUILD</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled Dose Escalation and Verification Clinical Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide (iNO) in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis on Long Term Oxygen Therapy (Part 1 and Part 2) - REBUILD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bellerophon Pulse Technologies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bellerophon</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, double-blind, placebo-controlled dose escalation and verification study to&#xD;
      assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for&#xD;
      pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1&#xD;
      and Part 2) - REBUILD&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 3, randomized, double-blind, placebo-controlled dose escalation and&#xD;
      verification clinical study to assess the safety and efficacy of pulsed inhaled nitric oxide&#xD;
      (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on&#xD;
      long term oxygen therapy (Part 1 and Part 2) - REBUILD&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The trial did not meet its primary endpoint, hence was terminated due to futility.&#xD;
  </why_stopped>
  <start_date type="Actual">December 14, 2020</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">June 9, 2023</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>Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 - Blinded Treatment Period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 2 - Open Label Extension (OLE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Overall Activity as Measured by Actigraphy</measure>
    <time_frame>Baseline to M4</time_frame>
    <description>Part 1 - Blinded Treatment Period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 Blinded Treatment Period: The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts &amp; Total</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 Blinded Treatment Period: SGRQ is a tool for assessing quality of life that has previously been validated for the use with patients with interstitial lung disease. It is a responsive tool that has three domains: symptoms, activity and impact (on daily life)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Worsening</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 - Blinded Treatment Period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Deterioration</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 Blinded Treatment Period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Clinical Improvement</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 Blinded Treatment Period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 6 Minute Walk Distance</measure>
    <time_frame>Baseline to Month 4</time_frame>
    <description>Part 1 Blinded Treatment Period</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">145</enrollment>
  <condition>Pulmonary Fibrosis</condition>
  <condition>Pulmonary Hypertension</condition>
  <arm_group>
    <arm_group_label>Inhaled Nitric Oxide (iNO)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pulsed inhaled iNO 45 mcg/kg Ideal Body Weight (IBW)/hour (hr)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Pulsed inhaled N2, 99.999% gas</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open Label Extension</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Pulsed inhaled iNO 45 mcg/kg IBW/hr</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>INOpulse®</intervention_name>
    <description>Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.</description>
    <arm_group_label>Inhaled Nitric Oxide (iNO)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Open Label Extension</intervention_name>
    <description>Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.</description>
    <arm_group_label>Open Label Extension</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  A high resolution CT scan performed in the 6 months prior to screening associated with&#xD;
             one of the following conditions and confirmed using guidelines, as per American&#xD;
             Thoracic Society (ATS) / European Respiratory Society (ERS) / Japanese Respiratory&#xD;
             Society (JRS) / Latin American Thoracic Association (ALAT):&#xD;
&#xD;
               -  Major IIPs (idiopathic interstitial pneumonias) diagnosis or suspected as one of&#xD;
                  the following:&#xD;
&#xD;
                    -  Idiopathic pulmonary fibrosis&#xD;
&#xD;
                    -  Idiopathic nonspecific interstitial pneumonia&#xD;
&#xD;
                    -  Respiratory bronchiolitis-interstitial lung disease&#xD;
&#xD;
                    -  Desquamative interstitial pneumonia&#xD;
&#xD;
                    -  Cryptogenic organizing pneumonia&#xD;
&#xD;
                    -  Acute interstitial pneumonia&#xD;
&#xD;
               -  Rare IIPs diagnosis by one of the following:&#xD;
&#xD;
                    -  Idiopathic lymphoid interstitial pneumonia&#xD;
&#xD;
                    -  Idiopathic pleuroparenchymal fibroelastosis&#xD;
&#xD;
               -  Unclassifiable idiopathic interstitial pneumonias&#xD;
&#xD;
                    -  Chronic hypersensitivity pneumonitis&#xD;
&#xD;
                    -  Occupational lung disease&#xD;
&#xD;
               -  Connective Tissue Disease associated with IPF (CTD-ILD)&#xD;
&#xD;
               -  Interstitial Pneumonia with Autoimmune Features (IPAF)&#xD;
&#xD;
          -  Have been using oxygen therapy by nasal cannula for at least 4 weeks (including use&#xD;
             limited to exertion)&#xD;
&#xD;
          -  6MWD ≥ 100 meters and ≤ 400 meters at screening and Baseline/Randomization visits.&#xD;
&#xD;
          -  World Health Organization (WHO) Functional Class II-IV&#xD;
&#xD;
          -  Forced Vital Capacity ≥ 40% predicted within the 60 day Screening period&#xD;
&#xD;
          -  Age between 18 and 80 years (inclusive) at screening&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  For women of child-bearing potential: Pregnant or breastfeeding females at Screening,&#xD;
             or planning to get pregnant, or unwilling to use appropriate contraception if sexually&#xD;
             active to avoid pregnancy during the study and for at least 30 days after&#xD;
             discontinuation of the study drug.&#xD;
&#xD;
          -  Heart failure with reduced ejection fraction (HFrEF; systolic heart failure) with an&#xD;
             ejection fraction of &lt; 40%; or severe HF with preserved EF (HFpEF; diastolic HF)&#xD;
&#xD;
          -  History of sarcoidosis&#xD;
&#xD;
          -  History of chronic thrombo-embolic pulmonary hypertension (CTEPH; WHO group 4 PH)&#xD;
&#xD;
          -  Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the&#xD;
             study&#xD;
&#xD;
          -  Body mass index (BMI) &gt;40 kg/m2 at screening&#xD;
&#xD;
          -  Intermittent uncontrolled atrial fibrillation, in the opinion of the Principal&#xD;
             Investigator&#xD;
&#xD;
          -  Known severe hepatic impairment, in the opinion of the Principal Investigator&#xD;
&#xD;
          -  Known severe renal impairment (Chronic Kidney Disease Epidemiology Collaboration&#xD;
             (CKDEPI) 2009 equation [Levy 2009] calculated creatinine clearance &lt;30 ml/min) at&#xD;
             screening&#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>Ashika Ahmed</last_name>
    <role>Study Director</role>
    <affiliation>Bellerophon Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner - University Medical Center Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Pulmonary Specialists, Ltd.</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amicis Research</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Paloma Medical Group</name>
      <address>
        <city>Paloma</city>
        <state>California</state>
        <zip>92675</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Health</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Denver Anschutz Medical Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Sleep Allergy and Lung Institute</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Pulmonary Research Institute</name>
      <address>
        <city>Loxahatchee Groves</city>
        <state>Florida</state>
        <zip>33470</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avanza Medical Research Center</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northside Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Healthcare</name>
      <address>
        <city>Austell</city>
        <state>Georgia</state>
        <zip>30106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore University Hospital</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loyola University</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Illinois University</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702 / 62794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension St. Vincent Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Pulmonary Specialists</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Lung Research Center, LLC</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Creighton University</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Health Respiratory Institute</name>
      <address>
        <city>Summit</city>
        <state>New Jersey</state>
        <zip>07901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University Hospital</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of North Carolina at Chapel Hill Marsico Clinical Research Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27517</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonix, LLC/LeBauer Cone Health</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oregon Clinic</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Korman Respiratory Institute</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19017</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>Temple University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AnMed Health</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metroplex Pulmonary and Sleep</name>
      <address>
        <city>McKinney</city>
        <state>Texas</state>
        <zip>75069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Health Sciences</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Heart and Vascular Institute Advanced Lung Disease Clinic</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of British Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen's University/Hotel Dieu Hospital</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <zip>K7L 5G2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>K7L 2V6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://rebuildstudy.com/</url>
    <description>Study website link</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulmonary Fibrosis</keyword>
  <keyword>PF</keyword>
  <keyword>Pulmonary Hypertension</keyword>
  <keyword>Inhaled Nitric Oxide</keyword>
  <keyword>iNO</keyword>
  <keyword>Long Term Oxygen Therapy</keyword>
  <keyword>Oxygen</keyword>
  <keyword>REBUILD</keyword>
  <keyword>INOpulse</keyword>
  <keyword>pulsed inhaled nitric oxide</keyword>
  <keyword>fILD</keyword>
  <keyword>fibrotic interstitial lung disease</keyword>
  <keyword>portable pulsed inhaled nitric oxide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 29, 2023</submitted>
    <returned>August 23, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03267108
org study id: PULSE-PHPF-001
nct id: NCT03267108
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
A randomized, double-blind, placebo-controlled dose escalation and verification study to
      assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for
      pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1
      and Part 2) - REBUILD
This is a Phase 3, randomized, double-blind, placebo-controlled dose escalation and
      verification clinical study to assess the safety and efficacy of pulsed inhaled nitric oxide
      (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on
      long term oxygen therapy (Part 1 and Part 2) - REBUILD
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy
time frame: Baseline to Month 4
description: Part 1 - Blinded Treatment Period
measure: Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy
time frame: Baseline to Month 4
description: Part 2 - Open Label Extension (OLE)
measure: Change in Overall Activity as Measured by Actigraphy
time frame: Baseline to M4
description: Part 1 - Blinded Treatment Period
measure: Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)
time frame: Baseline to Month 4
description: Part 1 Blinded Treatment Period: The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome).
measure: Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total
time frame: Baseline to Month 4
description: Part 1 Blinded Treatment Period: SGRQ is a tool for assessing quality of life that has previously been validated for the use with patients with interstitial lung disease. It is a responsive tool that has three domains: symptoms, activity and impact (on daily life)
measure: Time to Clinical Worsening
time frame: Baseline to Month 4
description: Part 1 - Blinded Treatment Period
measure: Time to Clinical Deterioration
time frame: Baseline to Month 4
description: Part 1 Blinded Treatment Period
measure: Time to Clinical Improvement
time frame: Baseline to Month 4
description: Part 1 Blinded Treatment Period
measure: Change in 6 Minute Walk Distance
time frame: Baseline to Month 4
description: Part 1 Blinded Treatment Period
arm group label: Inhaled Nitric Oxide (iNO)
arm group type: Active Comparator
description: Pulsed inhaled iNO 45 mcg/kg Ideal Body Weight (IBW)/hour (hr)
arm group label: Placebo
arm group type: Placebo Comparator
description: Pulsed inhaled N2, 99.999% gas
arm group label: Open Label Extension
arm group type: Other
description: Pulsed inhaled iNO 45 mcg/kg IBW/hr
intervention type: Combination Product
intervention name: INOpulse®
description: Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
arm group label: Inhaled Nitric Oxide (iNO)
intervention type: Combination Product
intervention name: Placebo
description: Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
arm group label: Placebo
intervention type: Combination Product
intervention name: Open Label Extension
description: Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
arm group label: Open Label Extension
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ashika Ahmed
role: Study Director
affiliation: Bellerophon Therapeutics
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country: Canada
country: United States
url: https://rebuildstudy.com/
description: Study website link
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Pulmonary Fibrosis
mesh term: Hypertension
mesh term: Fibrosis
sharing ipd: No
submitted: July 29, 2023
returned: August 23, 2023