<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/NCT03748992</url>
  </required_header>
  <id_info>
    <org_study_id>Pro 00081838</org_study_id>
    <nct_id>NCT03748992</nct_id>
  </id_info>
  <brief_title>A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection</brief_title>
  <official_title>A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cystic Fibrosis Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of South Carolina</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>
      The purpose of this study is to evaluate the efficacy and safety of open-label exposure of&#xD;
      gNO in patients with NTM lung disease. Subjects will receive the study drug by inhaling&#xD;
      through a nasal mask. Subjects will be treated for 3 weeks (5 days per week) and followed&#xD;
      monthly for 3 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2019</start_date>
  <completion_date type="Actual">March 26, 2020</completion_date>
  <primary_completion_date type="Actual">March 26, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Patients With Negative Sputum Culture</measure>
    <time_frame>End of Treatment (Day 15)</time_frame>
    <description>Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)</measure>
    <time_frame>Treatment Day 1 through End of Treatment (3 Months)</time_frame>
    <description>Adverse Events will be assessed by patient reporting and routine lab work</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Reduction in Semiquantitative Cultures</measure>
    <time_frame>At day 15 from baseline</time_frame>
    <description>Semiquantitative Culture Score is an assessment of bacterial burden with a lower score suggesting a lesser bacterial burden. The Semiquantitative Culture Score at Day 15 was compared to baseline, and a reduction in the Semiquantitative Culture Score suggests a reduced bacterial burden with treatment.&#xD;
Cultures were reported as positive if growth occurs in broth medium only; growth on broth medium plus solid medium cultures with countable colonies will be reported as 0-49 colonies, 1+; solid medium growth with 50-99 colonies, 2+; solid medium growth with 100-199 colonies; 3+, solid medium growth with 200-299 colonies; and 4+, solid medium growth with at least 300 colonies. For data analysis, each culture was scored as follows: 0, no growth in broth or solid medium; 1, broth medium growth only; 2, countable colonies (&lt;50 colonies) on solid medium; and 3-6, 1+ to 4+ growth on solid medium, respectively.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Nontuberculous Mycobacterium Infection</condition>
  <arm_group>
    <arm_group_label>gNO</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be receiving nitric oxide every week day for 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gNO</intervention_name>
    <description>This is a proof-of-concept study in which all subjects will be treated with gNO (i.e. no control) to see if there can be a microbiological effect by conversion to negative sputum cultures and how long that effect can be sustained following treatment.&#xD;
Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.&#xD;
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.</description>
    <arm_group_label>gNO</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects are &gt;18 years of age and able to provide informed consent.&#xD;
&#xD;
        Subjects have NTM lung disease as defined by each of the following:&#xD;
&#xD;
        Sputum cultures positive for NTM (MAC or M abscessus) Radiologic studies that demonstrate&#xD;
        features consistent with disease such as nodular bronchiectasis and/or cavities Symptoms&#xD;
        consistent with disease including respiratory (e.g. cough, sputum production, hemoptysis,&#xD;
        chest pain) and constitutional (e.g. fevers, night sweats, fatigue, myalgias, arthralgias,&#xD;
        weight loss) Subjects are able to produce sputum for culture (either spontaneous or&#xD;
        induced).&#xD;
&#xD;
        Subjects have a history of persistently positive sputum cultures for NTM defined as &gt;4&#xD;
        number of cultures over 24 months with &gt;75% positive AND a positive culture in the last 3&#xD;
        months.&#xD;
&#xD;
        Clinically stable with no significant changes in health status within 14 days prior to&#xD;
        Screening or Day 1 Subjects are willing and able to perform requirements of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Smoking history in the prior 6 months Significant hemoptysis within 30 days prior to&#xD;
        screening (&gt;5 ml of blood in one coughing episode or &gt;30 ml of blood in a 24 hour period)&#xD;
        Forced expiratory volume at one second (FEV1) &lt;40% of predicted On supplemental oxygen or&#xD;
        SaO2 &lt;90% at screening or Day 1, or within 30 days prior to enrollment.&#xD;
&#xD;
        Known cardiac (left heart) insufficiency (defined as LVEF &lt;35%) prior to screening Known&#xD;
        pulmonary hypertension Known or suspected hemoglobinopathy Initiation of NTM treatment&#xD;
        regimen or a change in the regimen was made in the prior 6 months. Subjects on active&#xD;
        treatment can be enrolled if they have been on a stable anti-NTM regimen for at least 6&#xD;
        months.&#xD;
&#xD;
        Initiation of new chronic therapy within 4 weeks prior to screening Use of drugs known to&#xD;
        increase methemoglobin (see 12.2.7) at screening&#xD;
&#xD;
        Any of the following abnormal lab values at screening:&#xD;
&#xD;
        6-GPD deficiency Hemoglobin &lt;10g/dl Platelet count &lt;100,000/mm3 Prothrombin time&#xD;
        international ratio (INR) &gt;1.5 Abnormal liver function defined as any two of the following&#xD;
        ALT &gt;3x ULN AST &gt;3x ULN ALP &gt;3x ULN GGT &gt;3x ULN&#xD;
&#xD;
        Abnormal renal function defined as:&#xD;
&#xD;
        Calculated Creatinine Clearance &lt;50 ml (as calculated by Cockcroft/Gault)&#xD;
&#xD;
        For women of child bearing potential:&#xD;
&#xD;
        Positive pregnancy test at screening or Lactating or Unwilling to practice a medically&#xD;
        acceptable form of contraception from screening to Day 15 (acceptable forms of&#xD;
        contraception: abstinence, hormonal birth control, intrauterine device, or barrier method&#xD;
        plus a spermicidal agent) Use of an investigational drug within 30 days prior to screening&#xD;
        Intravenous or oral steroids (&gt;10 mg/d prednisone equivalent) in the 14 days prior to&#xD;
        screening Any condition that the Investigator believes would interfere with the intent of&#xD;
        this study or would make participation not in the best interest of the subject.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick Flume</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <results_first_submitted>March 25, 2021</results_first_submitted>
  <results_first_submitted_qc>May 17, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 18, 2021</results_first_posted>
  <last_update_submitted>May 17, 2021</last_update_submitted>
  <last_update_submitted_qc>May 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Mycobacterium Infections</mesh_term>
    <mesh_term>Mycobacterium Infections, Nontuberculous</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03748992/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Inhaled Nitric Oxide (gNO)</title>
          <description>Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.&#xD;
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Inhaled Nitric Oxide (gNO)</title>
          <description>Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.&#xD;
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47.7" spread="24.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Patients With Negative Sputum Culture</title>
        <description>Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.</description>
        <time_frame>End of Treatment (Day 15)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (gNO)</title>
            <description>Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.&#xD;
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Patients With Negative Sputum Culture</title>
          <description>Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>This was a single arm trial. there is no comparator group.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since no hypothesis testing was planned, no power analysis was required</non_inferiority_desc>
            <other_analysis_desc>The overall response rates were calculated, and exact binomial confidence intervals was constructed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)</title>
        <description>Adverse Events will be assessed by patient reporting and routine lab work</description>
        <time_frame>Treatment Day 1 through End of Treatment (3 Months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (gNO)</title>
            <description>Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.&#xD;
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)</title>
          <description>Adverse Events will be assessed by patient reporting and routine lab work</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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Reduction in Semiquantitative Cultures</title>
        <description>Semiquantitative Culture Score is an assessment of bacterial burden with a lower score suggesting a lesser bacterial burden. The Semiquantitative Culture Score at Day 15 was compared to baseline, and a reduction in the Semiquantitative Culture Score suggests a reduced bacterial burden with treatment.&#xD;
Cultures were reported as positive if growth occurs in broth medium only; growth on broth medium plus solid medium cultures with countable colonies will be reported as 0-49 colonies, 1+; solid medium growth with 50-99 colonies, 2+; solid medium growth with 100-199 colonies; 3+, solid medium growth with 200-299 colonies; and 4+, solid medium growth with at least 300 colonies. For data analysis, each culture was scored as follows: 0, no growth in broth or solid medium; 1, broth medium growth only; 2, countable colonies (&lt;50 colonies) on solid medium; and 3-6, 1+ to 4+ growth on solid medium, respectively.</description>
        <time_frame>At day 15 from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Nitric Oxide (gNO)</title>
            <description>Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.&#xD;
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Reduction in Semiquantitative Cultures</title>
          <description>Semiquantitative Culture Score is an assessment of bacterial burden with a lower score suggesting a lesser bacterial burden. The Semiquantitative Culture Score at Day 15 was compared to baseline, and a reduction in the Semiquantitative Culture Score suggests a reduced bacterial burden with treatment.&#xD;
Cultures were reported as positive if growth occurs in broth medium only; growth on broth medium plus solid medium cultures with countable colonies will be reported as 0-49 colonies, 1+; solid medium growth with 50-99 colonies, 2+; solid medium growth with 100-199 colonies; 3+, solid medium growth with 200-299 colonies; and 4+, solid medium growth with at least 300 colonies. For data analysis, each culture was scored as follows: 0, no growth in broth or solid medium; 1, broth medium growth only; 2, countable colonies (&lt;50 colonies) on solid medium; and 3-6, 1+ to 4+ growth on solid medium, respectively.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>This was a single arm trial. there is no comparator group.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since no hypothesis testing was planned, no power analysis was required</non_inferiority_desc>
            <other_analysis_desc>The overall response rates were calculated, and exact binomial confidence intervals was constructed.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients were assessed for AE's throughout the duration of the study, approximately 3 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Inhaled Nitric Oxide (gNO)</title>
          <description>evaluate the efficacy and safety of open-label exposure of gNO in patients with NTM lung disease&#xD;
gNO: This is a proof-of-concept study in which all subjects will be treated with gNO (i.e. no control) to see if there can be a microbiological effect by conversion to negative sputum cultures and how long that effect can be sustained following treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <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="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Transient Ischemic Attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest tightness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hematochezia</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Night sweats</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Shingles</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pain/pleurisy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hemoptysis</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Sputum increased</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Patrick Flume, MD</name_or_title>
      <organization>Medical University of South Carolina</organization>
      <phone>843-792-3167</phone>
      <email>flumepa@musc.edu</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/NCT03748992
org study id: Pro 00081838
nct id: NCT03748992
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of open-label exposure of
      gNO in patients with NTM lung disease. Subjects will receive the study drug by inhaling
      through a nasal mask. Subjects will be treated for 3 weeks (5 days per week) and followed
      monthly for 3 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Patients With Negative Sputum Culture
time frame: End of Treatment (Day 15)
description: Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.
measure: Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)
time frame: Treatment Day 1 through End of Treatment (3 Months)
description: Adverse Events will be assessed by patient reporting and routine lab work
measure: Number of Participants With a Reduction in Semiquantitative Cultures
time frame: At day 15 from baseline
description: Semiquantitative Culture Score is an assessment of bacterial burden with a lower score suggesting a lesser bacterial burden. The Semiquantitative Culture Score at Day 15 was compared to baseline, and a reduction in the Semiquantitative Culture Score suggests a reduced bacterial burden with treatment.
Cultures were reported as positive if growth occurs in broth medium only; growth on broth medium plus solid medium cultures with countable colonies will be reported as 0-49 colonies, 1+; solid medium growth with 50-99 colonies, 2+; solid medium growth with 100-199 colonies; 3+, solid medium growth with 200-299 colonies; and 4+, solid medium growth with at least 300 colonies. For data analysis, each culture was scored as follows: 0, no growth in broth or solid medium; 1, broth medium growth only; 2, countable colonies (<50 colonies) on solid medium; and 3-6, 1+ to 4+ growth on solid medium, respectively.
arm group label: gNO
arm group type: Experimental
description: Subjects will be receiving nitric oxide every week day for 3 weeks.
intervention type: Drug
intervention name: gNO
description: This is a proof-of-concept study in which all subjects will be treated with gNO (i.e. no control) to see if there can be a microbiological effect by conversion to negative sputum cultures and how long that effect can be sustained following treatment.
Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.
arm group label: gNO
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Patrick Flume
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Mycobacterium Infections
mesh term: Mycobacterium Infections, Nontuberculous
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 