<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/NCT04421508</url>
  </required_header>
  <id_info>
    <org_study_id>PULSE-CVD19-001</org_study_id>
    <nct_id>NCT04421508</nct_id>
  </id_info>
  <brief_title>A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19</brief_title>
  <acronym>COViNOX</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)</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>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of&#xD;
      pulsed inhaled iNO compared to placebo in subjects with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled study to assess the efficacy and&#xD;
      safety of pulsed iNO compared to placebo in subjects with COVID-19 who are hospitalized and&#xD;
      require supplemental oxygen without assisted ventilation. Subjects will be randomized to&#xD;
      receive placebo or iNO125 mcg/kg ideal body weight (IBW)/hour 24 hours daily up to 14 days or&#xD;
      until resolution or discharge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Futility&#xD;
  </why_stopped>
  <start_date type="Actual">July 12, 2020</start_date>
  <completion_date type="Actual">January 22, 2021</completion_date>
  <primary_completion_date type="Actual">December 28, 2020</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>The Number of Subjects Who Died or Had Respiratory Failure</measure>
    <time_frame>Through Day 28</time_frame>
    <description>The number of subjects who died or had respiratory failure through Day 28</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects to Recover</measure>
    <time_frame>Through Day 28</time_frame>
    <description>Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</measure>
    <time_frame>Day 7</time_frame>
    <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</measure>
    <time_frame>Day 14</time_frame>
    <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</measure>
    <time_frame>Day 28</time_frame>
    <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Discharged Alive From Hospital</measure>
    <time_frame>Through Day 28</time_frame>
    <description>Number of subjects discharged alive from hospital through Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospitalization</measure>
    <time_frame>Through Day 28</time_frame>
    <description>Duration of Hospitalization through Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Cause Mortality</measure>
    <time_frame>Through Day 28</time_frame>
    <description>All cause mortality through Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Proportion in RT-PCR Results at Discharge by Treatment Group</measure>
    <time_frame>Through Day 28</time_frame>
    <description>Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Subjects With Adverse Events Leading to Study Drug Discontinuation</measure>
    <time_frame>Through Day 28</time_frame>
    <description>Number of subjects with adverse events leading to study drug discontinuation through Day 28</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">191</enrollment>
  <condition>COVID-19</condition>
  <condition>Coronavirus</condition>
  <condition>Coronavirus Infection</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 125 mcg/kg IBW/hour</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Pulsed inhaled N2, 99.999% gas</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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  At least 18 years old&#xD;
&#xD;
          -  Subjects must be hospitalized and have the following:&#xD;
&#xD;
               -  proven or high suspicion of SARS-CoV-2 infection and,&#xD;
&#xD;
               -  requiring oxygen supplementation defined as:&#xD;
&#xD;
               -  SpO2 ≤ 92% regardless of supplemental oxygen (ie on room air or on oxygen), or&#xD;
&#xD;
               -  SpO2 ≥ 92% on supplemental O2 and in the opinion of the Investigator it is not&#xD;
                  safe to decrease or remove the supplemental oxygen&#xD;
&#xD;
               -  require supplemental oxygen of no more than 10 L/minute, and&#xD;
&#xD;
               -  radiologic suspected or proven COVID-19 pneumonitis (chest x-ray or CT scan)&#xD;
&#xD;
          -  Female subjects must have a negative pregnancy test&#xD;
&#xD;
          -  Willing and able to comply with the treatment schedule and study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participating in another clinical trial of an investigational treatment for COVID-19&#xD;
&#xD;
          -  Methemoglobin &gt; 3%&#xD;
&#xD;
          -  Evidence of severe multi organ failure&#xD;
&#xD;
          -  Use of assisted ventilation prior to initiation of iNO&#xD;
&#xD;
          -  Pregnancy or positive pregnancy test pre-dose&#xD;
&#xD;
          -  Open tracheostomy&#xD;
&#xD;
          -  Chronic use of a nitric oxide donor agent such as nitroglycerin or drugs known to&#xD;
             increase methemoglobin such as lidocaine, prilocaine, benzocaine, nitroprusside,&#xD;
             isosorbide, or dapsone at screening&#xD;
&#xD;
          -  History or clinical evidence of systolic heart failure, left ventricular dysfunction&#xD;
             (LVEF &lt;40%)&#xD;
&#xD;
          -  Subjects reporting massive hemoptysis associated with the current illness or with&#xD;
             radiologically proven pulmonary embolus&#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>Ashika Ahmed, MD</last_name>
    <role>Study Director</role>
    <affiliation>Bellerophon Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner University Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Zion Medical Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - San Diego Medical Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Health System</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Lung Research Center (St. Luke's)</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Hospital</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Health St. Vincent Medical Center</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INOVA</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Regional Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chippenham Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Mary's Hospital</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johnston-Willis Hospital</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <results_first_submitted>May 30, 2022</results_first_submitted>
  <results_first_submitted_qc>January 5, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 1, 2023</results_first_posted>
  <last_update_submitted>February 17, 2023</last_update_submitted>
  <last_update_submitted_qc>February 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID</keyword>
  <keyword>Sars-CoV-2</keyword>
  <keyword>iNO</keyword>
  <keyword>INOpulse</keyword>
  <keyword>Severe Acute Respiratory Syndrome (SARS) Pneumonia</keyword>
  <keyword>Severe Acute Respiratory Syndrome Coronavirus 2</keyword>
  <keyword>SARS-CoV 2</keyword>
  <keyword>COViNOX</keyword>
  <keyword>pulsed inhaled nitric oxide</keyword>
  <keyword>inhaled nitric oxide</keyword>
  <keyword>portable pulsed inhaled nitric oxide</keyword>
  <keyword>nitric oxide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT04421508/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 26, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT04421508/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Inhaled Nitric Oxide (iNO)</title>
          <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="95"/>
                <participants group_id="P2" count="96"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="91"/>
                <participants group_id="P2" count="95"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All Randomized Analysis Set</population>
      <group_list>
        <group group_id="B1">
          <title>Inhaled Nitric Oxide (iNO)</title>
          <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</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="95"/>
            <count group_id="B2" value="96"/>
            <count group_id="B3" value="191"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>1 age value missing in Placebo group</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="95"/>
                    <count group_id="B3" value="190"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="121"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="69"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.0" spread="14.96"/>
                    <measurement group_id="B2" value="59.1" spread="13.72"/>
                    <measurement group_id="B3" value="58.6" spread="14.33"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="99"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="130"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>America Indian or Alaska Native</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </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>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                    <measurement group_id="B2" value="96"/>
                    <measurement group_id="B3" value="191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Number of Subjects Who Died or Had Respiratory Failure</title>
        <description>The number of subjects who died or had respiratory failure through Day 28</description>
        <time_frame>Through Day 28</time_frame>
        <population>All Randomized Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Subjects Who Died or Had Respiratory Failure</title>
          <description>The number of subjects who died or had respiratory failure through Day 28</description>
          <population>All Randomized Analysis Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6316</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4127</p_value>
            <p_value_desc>Odds ratio, 95% CI and p-value are from a logistic regression model modelling the response using the covariates treatment, age, number of co-morbidities and baseline oxygem level</p_value_desc>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.502</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.567</ci_lower_limit>
            <ci_upper_limit>3.977</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects to Recover</title>
        <description>Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.</description>
        <time_frame>Through Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects to Recover</title>
          <description>Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.</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="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Recovered</title>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Recovered</title>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                    <measurement group_id="O2" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</title>
        <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
        <time_frame>Day 7</time_frame>
        <population>All Randomized Analysis Set with NIAID scores at Day 7</population>
        <group_list>
          <group group_id="O1">
            <title>Pulsed Inhaled iNO 125 mcg/kg IBW/Hour</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo N2, 99.999% Gas</title>
            <description>Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</title>
          <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
          <population>All Randomized Analysis Set with NIAID scores at Day 7</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
                <count group_id="O2" value="85"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.28" spread="0.198"/>
                    <measurement group_id="O2" value="5.81" spread="0.192"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</title>
        <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
        <time_frame>Day 14</time_frame>
        <population>All Randomized Analysis Set with NIAID scores at Day 14</population>
        <group_list>
          <group group_id="O1">
            <title>Pulsed Inhaled iNO 125 mcg/kg IBW/Hour</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo N2, 99.999% Gas</title>
            <description>Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</title>
          <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
          <population>All Randomized Analysis Set with NIAID scores at Day 14</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.22" spread="0.208"/>
                    <measurement group_id="O2" value="6.38" spread="0.202"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</title>
        <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
        <time_frame>Day 28</time_frame>
        <population>All Randomized Analysis Set with NIAID scores at Day 28</population>
        <group_list>
          <group group_id="O1">
            <title>Pulsed Inhaled iNO 125 mcg/kg IBW/Hour</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo N2, 99.999% Gas</title>
            <description>Pulsed inhaled N2, 99.999% gas Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale</title>
          <description>The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.</description>
          <population>All Randomized Analysis Set with NIAID scores at Day 28</population>
          <units>score on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.56" spread="0.193"/>
                    <measurement group_id="O2" value="6.87" spread="0.186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects Discharged Alive From Hospital</title>
        <description>Number of subjects discharged alive from hospital through Day 28</description>
        <time_frame>Through Day 28</time_frame>
        <population>(1) Discharged is defined as discharged alive from hospital through day 28. (2) For patients who were randomized but not treated, the date of randomization is used in place of the treatment start date.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Discharged Alive From Hospital</title>
          <description>Number of subjects discharged alive from hospital through Day 28</description>
          <population>(1) Discharged is defined as discharged alive from hospital through day 28. (2) For patients who were randomized but not treated, the date of randomization is used in place of the treatment start date.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Discharged</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89"/>
                    <measurement group_id="O2" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Discharged</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing Data</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospitalization</title>
        <description>Duration of Hospitalization through Day 28</description>
        <time_frame>Through Day 28</time_frame>
        <population>(1) Subject hospital duration will be defined as the time from Day 1 (start of study treatment) to the day of hospital discharge or Day 28 of treatment for patients who are still hospitalized. If a patient has expired on or before Day 27 of treatment, they will be assigned a value of 28 days. (2) For patients who were randomized but not treated, the date of randomization is used in place of the treatment start date.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospitalization</title>
          <description>Duration of Hospitalization through Day 28</description>
          <population>(1) Subject hospital duration will be defined as the time from Day 1 (start of study treatment) to the day of hospital discharge or Day 28 of treatment for patients who are still hospitalized. If a patient has expired on or before Day 27 of treatment, they will be assigned a value of 28 days. (2) For patients who were randomized but not treated, the date of randomization is used in place of the treatment start date.</population>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.9" spread="6.58"/>
                    <measurement group_id="O2" value="8.1" spread="6.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>All Cause Mortality</title>
        <description>All cause mortality through Day 28</description>
        <time_frame>Through Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>All Cause Mortality</title>
          <description>All cause mortality through Day 28</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="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Difference in Proportion in RT-PCR Results at Discharge by Treatment Group</title>
        <description>Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.</description>
        <time_frame>Through Day 28</time_frame>
        <population>Difference in converted RT-PCR Results at Discharge by Treatment Group. Only participants with a positive RT-PCR result at baseline are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in Proportion in RT-PCR Results at Discharge by Treatment Group</title>
          <description>Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.</description>
          <population>Difference in converted RT-PCR Results at Discharge by Treatment Group. Only participants with a positive RT-PCR result at baseline are included in the analysis.</population>
          <units>Proportion Converted</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Positive RT-PCR Result</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.841" lower_limit="0.751" upper_limit="0.932"/>
                    <measurement group_id="O2" value="0.812" lower_limit="0.719" upper_limit="0.904"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative RT-PCR Result</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.159" lower_limit="0.068" upper_limit="0.249"/>
                    <measurement group_id="O2" value="0.188" lower_limit="0.096" upper_limit="0.281"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6635</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Subjects With Adverse Events Leading to Study Drug Discontinuation</title>
        <description>Number of subjects with adverse events leading to study drug discontinuation through Day 28</description>
        <time_frame>Through Day 28</time_frame>
        <population>Full Safety Set</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (iNO)</title>
            <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Adverse Events Leading to Study Drug Discontinuation</title>
          <description>Number of subjects with adverse events leading to study drug discontinuation through Day 28</description>
          <population>Full Safety Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="91"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Collected during the study duration that includes 14 days within randomization to 30 days post last day of treatment (up to 28 days of blinded treatment)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Inhaled Nitric Oxide (iNO)</title>
          <description>Pulsed inhaled iNO 125 mcg/kg IBW/hour&#xD;
INOpulse: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Pulsed inhaled N2, 99.999% gas&#xD;
Placebo: Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (23.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Septic Shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Enterococcal bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Transfusion reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hemianopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="91"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (23.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="91"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hypercoagulation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual impariment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Eye swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>SARS-CoV-2 sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Vulvovaginal mycotic infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Transfusion reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Heart rate decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Vitamin D decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Cerebellar infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucination, visual</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Nasal discomfort</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="91"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Plural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Pneumomediastinum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Increased bronchial secretion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Nasal dryness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Rales</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Sputum discolored</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="91"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="95"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Bobae Kim</name_or_title>
      <organization>Bellerophon Therapeutics</organization>
      <phone>(917) 675-2254</phone>
      <email>bobae.kim@bellerophon.com</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/NCT04421508
org study id: PULSE-CVD19-001
nct id: NCT04421508
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of
      pulsed inhaled iNO compared to placebo in subjects with COVID-19.
This is a randomized, double-blind, placebo-controlled study to assess the efficacy and
      safety of pulsed iNO compared to placebo in subjects with COVID-19 who are hospitalized and
      require supplemental oxygen without assisted ventilation. Subjects will be randomized to
      receive placebo or iNO125 mcg/kg ideal body weight (IBW)/hour 24 hours daily up to 14 days or
      until resolution or discharge.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The Number of Subjects Who Died or Had Respiratory Failure
time frame: Through Day 28
description: The number of subjects who died or had respiratory failure through Day 28
measure: Number of Subjects to Recover
time frame: Through Day 28
description: Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.
measure: Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
time frame: Day 7
description: The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
measure: Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
time frame: Day 14
description: The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
measure: Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
time frame: Day 28
description: The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
measure: Number of Subjects Discharged Alive From Hospital
time frame: Through Day 28
description: Number of subjects discharged alive from hospital through Day 28
measure: Duration of Hospitalization
time frame: Through Day 28
description: Duration of Hospitalization through Day 28
measure: All Cause Mortality
time frame: Through Day 28
description: All cause mortality through Day 28
measure: Difference in Proportion in RT-PCR Results at Discharge by Treatment Group
time frame: Through Day 28
description: Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.
measure: Number of Subjects With Adverse Events Leading to Study Drug Discontinuation
time frame: Through Day 28
description: Number of subjects with adverse events leading to study drug discontinuation through Day 28
arm group label: Inhaled Nitric Oxide (iNO)
arm group type: Active Comparator
description: Pulsed inhaled iNO 125 mcg/kg IBW/hour
arm group label: Placebo
arm group type: Sham Comparator
description: Pulsed inhaled N2, 99.999% gas
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
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ashika Ahmed, MD
role: Study Director
affiliation: Bellerophon Therapeutics
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country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 