<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/NCT03015402</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY20010014</org_study_id>
    <secondary_id>5P01HL103455</secondary_id>
    <nct_id>NCT03015402</nct_id>
  </id_info>
  <brief_title>Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction</brief_title>
  <acronym>PH-HFpEF</acronym>
  <official_title>Phase II Clinical Investigation of Oral Nitrite in Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (PH-HFpEF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gladwin, Mark, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</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 main objective of this study is to determine the clinical efficacy of oral inorganic&#xD;
      nitrite verses placebo and the therapeutic response with regards to exercise tolerance in&#xD;
      patients with pulmonary hypertension and heart failure with preserved ejection fraction&#xD;
      (PH-HFpEF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, 22-week double-blind, randomized placebo-controlled cross-over trial&#xD;
      of oral nitrite on exercise capacity and hemodynamic measurements in subjects with PH-HFpEF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">January 25, 2023</completion_date>
  <primary_completion_date type="Actual">January 25, 2023</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and nitrite</measure>
    <time_frame>10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite).</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in 6-minute walk test</measure>
    <time_frame>10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)</time_frame>
    <description>Assessed using Borg dyspnea scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in right heart catheterization (RHC) hemodynamics</measure>
    <time_frame>10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)</time_frame>
    <description>RHC hemodynamic measures will be aggregated to determine if overall hemodynamic are improved over the course of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in severity of heart failure</measure>
    <time_frame>10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)</time_frame>
    <description>Determined by NT-proBNP plasma levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in endurance exercise time</measure>
    <time_frame>10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in severity of heart failure</measure>
    <time_frame>10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)</time_frame>
    <description>Determined by NYHA functional classification changes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Pulmonary Hypertension Secondary</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Sodium Nitrite</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Nitrite</intervention_name>
    <description>40 mg PO (by mouth) TID (three times each day) for 10 weeks</description>
    <arm_group_label>Sodium Nitrite</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Placebo capsule that is of identical size, shape, and color to experimental drug capsule PO (by mouth) TID (three times each day) for 10 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age 18 years and older&#xD;
&#xD;
        PH-HFpEF confirmed diagnosis by RHC:&#xD;
&#xD;
          -  Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mmHg AND&#xD;
&#xD;
          -  Pulmonary capillary wedge pressure (PWCP) ≥ 15 mmHg AND&#xD;
&#xD;
          -  Transpulmonary Gradient (TPG) ≥ 12 mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18 years;&#xD;
&#xD;
          -  SBP &gt; 170 or &lt; 110 mmHg&#xD;
&#xD;
          -  DBP &gt;95 or &lt; 60 mmHg&#xD;
&#xD;
          -  Hemoglobin A1C &gt; 10&#xD;
&#xD;
          -  Positive urine pregnancy test or breastfeeding;&#xD;
&#xD;
          -  Ejection Fraction (EF) &lt; 40%;&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  End-stage malignancy&#xD;
&#xD;
          -  Major cardiovascular event or procedure within 6 weeks prior to enrollment&#xD;
&#xD;
          -  Severe valvular disease&#xD;
&#xD;
          -  Known chronic psychiatric or medical conditions that may increase the risk associated&#xD;
             with study participation in the judgment of the investigator, would make the subject&#xD;
             inappropriate for entry into this study;&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Hemoglobin &lt;9 g/dL&#xD;
&#xD;
          -  Serum creatinine &gt; 3.0 mg/dL&#xD;
&#xD;
          -  Receipt of an investigational product or device, or participation in a drug research&#xD;
             study within a period of 15 days; RHC &lt; 2 weeks from study screening RHC unless&#xD;
             clinically indicated&#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>Michael Risbano, MD, MA</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>April 7, 2023</last_update_submitted>
  <last_update_submitted_qc>April 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Michael Risbano</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03015402
org study id: STUDY20010014
secondary id: 5P01HL103455
nct id: NCT03015402
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main objective of this study is to determine the clinical efficacy of oral inorganic
      nitrite verses placebo and the therapeutic response with regards to exercise tolerance in
      patients with pulmonary hypertension and heart failure with preserved ejection fraction
      (PH-HFpEF).
This is a single-center, 22-week double-blind, randomized placebo-controlled cross-over trial
      of oral nitrite on exercise capacity and hemodynamic measurements in subjects with PH-HFpEF.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and nitrite
time frame: 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite).
measure: Difference in 6-minute walk test
time frame: 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
description: Assessed using Borg dyspnea scale
measure: Change in right heart catheterization (RHC) hemodynamics
time frame: 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
description: RHC hemodynamic measures will be aggregated to determine if overall hemodynamic are improved over the course of treatment
measure: Change in severity of heart failure
time frame: 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
description: Determined by NT-proBNP plasma levels
measure: Change in endurance exercise time
time frame: 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
measure: Change in severity of heart failure
time frame: 10 weeks (i.e. the 10th week of placebo vs 10th week of nitrite)
description: Determined by NYHA functional classification changes
arm group label: Sodium Nitrite
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Sodium Nitrite
description: 40 mg PO (by mouth) TID (three times each day) for 10 weeks
arm group label: Sodium Nitrite
intervention type: Drug
intervention name: Placebo Oral Capsule
description: Placebo capsule that is of identical size, shape, and color to experimental drug capsule PO (by mouth) TID (three times each day) for 10 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Risbano, MD, MA
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Michael Risbano
investigator title: Assistant Professor of Medicine
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Heart Failure