<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/NCT02262078</url>
  </required_header>
  <id_info>
    <org_study_id>14-005091</org_study_id>
    <secondary_id>R01HL128526</secondary_id>
    <secondary_id>U10HL110262</secondary_id>
    <nct_id>NCT02262078</nct_id>
  </id_info>
  <brief_title>Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction</brief_title>
  <official_title>Acute Effects of Inhaled Sodium Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aires Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that&#xD;
      has no proven effective treatment. This study will assess the effects of nebulized inhaled&#xD;
      nitrite administration on resting and exercise hemodynamics in patients with HFpEF referred&#xD;
      to the catheterization lab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients referred to the cardiac catheterization laboratory for invasive exercise stress&#xD;
      testing will be prospectively recruited. Standard right heart catheterization using high&#xD;
      fidelity micromanometers (Millar Instruments) will be performed at rest and during supine&#xD;
      exercise with simultaneous expired gas analysis (Medgraphics) as is the investigator's&#xD;
      current practice. The protocol is rest-passive leg elevation--20 Watts exercise x 5 minutes,&#xD;
      and then graded workload increases in 10Watt increments (3 minute stages) to exhaustion.&#xD;
      Hemodynamic, arterial and mixed venous blood gas and expired gas data are acquired at rest,&#xD;
      during each exercise stage and at peak exercise. Venous blood samples will be obtained at&#xD;
      rest and at peak exercise. Perceived symptoms of dyspnea and fatigue will be quantified using&#xD;
      the Borg dyspnea and effort scores at each stage of exercise.&#xD;
&#xD;
      After the initial exercise study and hemodynamics have returned to baseline, previously&#xD;
      prepared study drug (normal saline placebo or Sodium Nitrite Inhalation Solution (AIR001)&#xD;
      90mg placed into the medication chamber) will be nebulized utilizing the Aerogen&#xD;
      Solo-Idehaler over 10-15 minutes. After a 15 minute observation period post completion of&#xD;
      nebulization, resting hemodynamic and expired gas data will be acquired exactly as in the&#xD;
      initial run. Subjects will then repeat the leg elevation-20 Watt x 5 minutes exercise phase.&#xD;
      Blood samples will be again obtained at rest and with exercise. Subjects will repeat exercise&#xD;
      only at the 20 Watt stage, rather repeating the entire study. This is done to increase the&#xD;
      feasibility and shorten the time of the case. The investigators have previously observed that&#xD;
      the vast majority (&gt;85%) of the elevation in cardiac filling pressures and reduction in&#xD;
      venous oxygen content in people with HFpEF occurs at the low 20 Watt workload, so repeating&#xD;
      exercise hemodynamic assessment at this load should be sufficient to detect any clinically&#xD;
      meaningful treatment effect.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Pulmonary Capillary Wedge Pressure During Exercise</measure>
    <time_frame>Baseline, after study drug dosing, approximately 4 minutes after starting exercise</time_frame>
    <description>Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Placebo (Saline)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sodium Nitrite</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Nitrite Inhalation Solution</intervention_name>
    <description>90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.</description>
    <arm_group_label>Sodium Nitrite</arm_group_label>
    <other_name>AIR001, NaNO2, Sodium Nitrite</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Normal saline will be administered (by inhalation) to participants prior to exercise.</description>
    <arm_group_label>Placebo (Saline)</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Heart Failure with preserved Ejection Fraction (HFpEF) is defined by clinical symptoms&#xD;
             of dyspnea and fatigue&#xD;
&#xD;
          -  Normal left ventricular ejection fraction (&gt;/=50%)&#xD;
&#xD;
          -  And elevated Left Ventricular (LV) filling pressure at cardiac catheterization&#xD;
             (defined as resting Pulmonary Capillary Wedge Pressure (PCWP)&gt;15 mmHg and/or PCWP&#xD;
             &gt;/=25 mmHg during exercise).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Systolic Blood Pressure &lt;120 mmHg (during catheterization)&#xD;
&#xD;
          -  Prior nitrate therapy (within previous 2 weeks)&#xD;
&#xD;
          -  Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency&#xD;
&#xD;
          -  Other &quot;non-HFpEF&quot; specific causes of heart failure such as significant valvular&#xD;
             disease (&gt;moderate left-sided regurgitation, &gt;mild stenosis)&#xD;
&#xD;
          -  Severe pulmonary disease&#xD;
&#xD;
          -  Unstable coronary disease or coronary spasm&#xD;
&#xD;
          -  Primary renal or hepatic disease (end stage renal failure/on dialysis or clinical&#xD;
             diagnosis of hepatitis or hepatic cirrhosis)&#xD;
&#xD;
          -  Constrictive pericarditis, or infiltrative, restrictive, or hypertrophic&#xD;
             cardiomyopathies&#xD;
&#xD;
          -  Pregnant&#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>Barry Borlaug, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Borlaug BA, Melenovsky V, Koepp KE. Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Circ Res. 2016 Sep 16;119(7):880-6. doi: 10.1161/CIRCRESAHA.116.309184. Epub 2016 Jul 25.</citation>
    <PMID>27458234</PMID>
  </results_reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <results_first_submitted>November 21, 2016</results_first_submitted>
  <results_first_submitted_qc>November 21, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 19, 2017</results_first_posted>
  <last_update_submitted>July 31, 2017</last_update_submitted>
  <last_update_submitted_qc>July 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Barry Borlaug</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Preserved Ejection Fraction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were referred to the Rochester, Minnesota Mayo Clinic cardiac catheterization laboratory for invasive hemodynamic exercise stress testing between December 2014 and December 2015.</recruitment_details>
      <pre_assignment_details>Of 70 patients screened, 32 were excluded based upon entry criteria and 12 were excluded based on hemodynamic criteria for Heart Failure with preserved Ejection Fraction (HFpEF) (n=10) or because arterial pressures were too low (n=2).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo (Saline)</title>
          <description>Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Placebo: Normal saline will be administered (by inhalation) to participants prior to exercise.</description>
        </group>
        <group group_id="P2">
          <title>Sodium Nitrite</title>
          <description>Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Sodium Nitrite Inhalation Solution: 90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo (Saline)</title>
          <description>Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Placebo: Normal saline will be administered (by inhalation) to participants prior to exercise.</description>
        </group>
        <group group_id="B2">
          <title>Sodium Nitrite</title>
          <description>Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Sodium Nitrite Inhalation Solution: 90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.</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="13"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="26"/>
          </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="72" spread="10"/>
                    <measurement group_id="B2" value="67" spread="9"/>
                    <measurement group_id="B3" value="70" spread="10"/>
                  </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="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_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="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Pulmonary Capillary Wedge Pressure During Exercise</title>
        <description>Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)</description>
        <time_frame>Baseline, after study drug dosing, approximately 4 minutes after starting exercise</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Saline)</title>
            <description>Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Placebo: Normal saline will be administered (by inhalation) to participants prior to exercise.</description>
          </group>
          <group group_id="O2">
            <title>Sodium Nitrite</title>
            <description>Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Sodium Nitrite Inhalation Solution: 90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pulmonary Capillary Wedge Pressure During Exercise</title>
          <description>Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)</description>
          <units>millimeters of mercury</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1" spread="2"/>
                    <measurement group_id="O2" value="-4" spread="3"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.002</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From baseline to X hours following treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo (Saline)</title>
          <description>Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Placebo: Normal saline will be administered (by inhalation) to participants prior to exercise.</description>
        </group>
        <group group_id="E2">
          <title>Sodium Nitrite</title>
          <description>Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer&#xD;
Sodium Nitrite Inhalation Solution: 90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Vasovagal syncope</sub_title>
                <description>One episode of vasovagal syncope 4 hours after completing study</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Taste perversion</sub_title>
                <description>Salty taste following the nebulizer treatment</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </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>
    <limitations_and_caveats>Patients with symptoms that might independently cause symptoms were excluded, including severe valvular or coronary heart disease and advanced lung, liver or kidney disease. Cannot determine if results would apply to these co-morbidities.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Barry A. Borlaug, MD</name_or_title>
      <organization>Mayo Clinic</organization>
      <email>Borlaug.Barry@mayo.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/NCT02262078
org study id: 14-005091
secondary id: R01HL128526
secondary id: U10HL110262
nct id: NCT02262078
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that
      has no proven effective treatment. This study will assess the effects of nebulized inhaled
      nitrite administration on resting and exercise hemodynamics in patients with HFpEF referred
      to the catheterization lab.
Patients referred to the cardiac catheterization laboratory for invasive exercise stress
      testing will be prospectively recruited. Standard right heart catheterization using high
      fidelity micromanometers (Millar Instruments) will be performed at rest and during supine
      exercise with simultaneous expired gas analysis (Medgraphics) as is the investigator's
      current practice. The protocol is rest-passive leg elevation--20 Watts exercise x 5 minutes,
      and then graded workload increases in 10Watt increments (3 minute stages) to exhaustion.
      Hemodynamic, arterial and mixed venous blood gas and expired gas data are acquired at rest,
      during each exercise stage and at peak exercise. Venous blood samples will be obtained at
      rest and at peak exercise. Perceived symptoms of dyspnea and fatigue will be quantified using
      the Borg dyspnea and effort scores at each stage of exercise.

      After the initial exercise study and hemodynamics have returned to baseline, previously
      prepared study drug (normal saline placebo or Sodium Nitrite Inhalation Solution (AIR001)
      90mg placed into the medication chamber) will be nebulized utilizing the Aerogen
      Solo-Idehaler over 10-15 minutes. After a 15 minute observation period post completion of
      nebulization, resting hemodynamic and expired gas data will be acquired exactly as in the
      initial run. Subjects will then repeat the leg elevation-20 Watt x 5 minutes exercise phase.
      Blood samples will be again obtained at rest and with exercise. Subjects will repeat exercise
      only at the 20 Watt stage, rather repeating the entire study. This is done to increase the
      feasibility and shorten the time of the case. The investigators have previously observed that
      the vast majority (>85%) of the elevation in cardiac filling pressures and reduction in
      venous oxygen content in people with HFpEF occurs at the low 20 Watt workload, so repeating
      exercise hemodynamic assessment at this load should be sufficient to detect any clinically
      meaningful treatment effect.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Pulmonary Capillary Wedge Pressure During Exercise
time frame: Baseline, after study drug dosing, approximately 4 minutes after starting exercise
description: Pulmonary capillary wedge pressure is a measure of cardiac filling pressure, measured in millimeters of mercury (mmHg)
arm group label: Placebo (Saline)
arm group type: Placebo Comparator
description: Participants receive normal saline, administered by inhalation over 10-15 minutes, using a nebulizer
arm group label: Sodium Nitrite
arm group type: Experimental
description: Participants receive Sodium Nitrite inhalation solution, administered by inhalation over 10-15 minutes, using a nebulizer
intervention type: Drug
intervention name: Sodium Nitrite Inhalation Solution
description: 90mg of (nebulized) inhaled sodium nitrite will be administered (by inhalation) to participants prior to exercise.
arm group label: Sodium Nitrite
other name: AIR001, NaNO2, Sodium Nitrite
intervention type: Other
intervention name: Placebo
description: Normal saline will be administered (by inhalation) to participants prior to exercise.
arm group label: Placebo (Saline)
other name: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Barry Borlaug, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
citation: Borlaug BA, Melenovsky V, Koepp KE. Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction. Circ Res. 2016 Sep 16;119(7):880-6. doi: 10.1161/CIRCRESAHA.116.309184. Epub 2016 Jul 25.
PMID: 27458234
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Barry Borlaug
investigator title: Principal Investigator
mesh term: Heart Failure
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Patients with symptoms that might independently cause symptoms were excluded, including severe valvular or coronary heart disease and advanced lung, liver or kidney disease. Cannot determine if results would apply to these co-morbidities.
point of contact: 