<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/NCT01717209</url>
  </required_header>
  <id_info>
    <org_study_id>25471</org_study_id>
    <nct_id>NCT01717209</nct_id>
  </id_info>
  <brief_title>Inhaled Nitric Oxide and Inhaled Prostacyclin After Cardiac Surgery for Heart Transplant or LVAD Placement</brief_title>
  <official_title>Combined Inhaled Nitric Oxide and Inhaled Prostacyclin After Cardiac Surgery for Heart Transplantation and for Left Ventricular Assist Device Placement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Research study evaluating the individual and combined effects of inhaled nitric oxide (iNO)&#xD;
      and inhaled prostacyclin (iPGI2), on the function of the right heart after surgery for either&#xD;
      heart transplant or for left ventricular assist device (LVAD) placement. The investigators&#xD;
      hope to learn if these two medications, when given together after surgery, improve right&#xD;
      heart function by lowering blood vessel pressures in the lungs. The investigators hope to&#xD;
      learn if the combined effects of these two medications are better than either medication used&#xD;
      alone. Participants were selected as a possible participant in this study because right heart&#xD;
      problems are common during and after surgery for heart transplant and for LVAD placement. In&#xD;
      addition, iNO is always given during and after these two types of surgeries at Stanford to&#xD;
      help improve how the right heart functions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will begin once the participant arrives in the cardiothoracic intensive care unit&#xD;
      (CTICU) after heart surgery for either heart transplant or LVAD placement. As is standard of&#xD;
      care after these types of surgeries, the participant will arrive in the CTICU with a&#xD;
      breathing tube already in place, receiving iNO, and connected to a breathing machine. The&#xD;
      participant will be receiving relaxing medication in an intravenous line provided by the&#xD;
      cardiac anesthesiologist and the CTICU physicians. The participant will be unaware of the&#xD;
      study period while the participant is sedated. Data will be collected from the monitor screen&#xD;
      connected to the participant's arterial and venous lines, and if placed, LVAD monitor. These&#xD;
      data are:&#xD;
&#xD;
      Central venous pressure (CVP) Mean arterial pressure (MAP) Mean pulmonary artery pressure&#xD;
      (MPAP) Cardiac Index (CI) Systemic vascular resistance (SVR) Pulmonary vascular resistance&#xD;
      (PVR) Right ventricular stroke work index (RVSWI) LVAD Flow LVAD Pulsatility Index (PI)&#xD;
&#xD;
      These data will be collected at five different time periods during the first eight hours&#xD;
      after surgery.&#xD;
&#xD;
        1. Time zero. Data will be collected after surgery upon your arrival to the CTICU while&#xD;
           receiving iNO.&#xD;
&#xD;
        2. After two hours of iNO treatment data will be collected. iPGI2 will then be combined&#xD;
           with the current iNO.&#xD;
&#xD;
        3. After two hours of combined iNO and iPGI2 treatment, data will be collected. iNO will&#xD;
           then be stopped.&#xD;
&#xD;
        4. After two hours of iPGI2 treatment data will be collected. iNO will be restarted.&#xD;
&#xD;
        5. After two hours of combined iNO and iPGI2 treatment, data will be collected. The study&#xD;
           ends after this data collection time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <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>Pulmonary Hypertension</measure>
    <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
    <description>Pulmonary hypertension was measured as mean of Mean Pulmonary Artery Pressure for initial 8 hours after admission to the Intensive Care Unit (ICU). MPAP value ≥25 mmHg (resting) indicates pulmonary hypertension state.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Right Heart Dysfunction</measure>
    <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
    <description>Right Heart Dysfunction was measured as mean of Right Ventricular Stroke Work Index (RVSWI) for the initial 8 hours after admission to the Intensive Care Unit (ICU). RVSWI is measured as the difference in mean pulmonary artery pressure (MPAP) and central venous pressure (CVP), divided by the cardiac index (CI): [(MPAP-CVP) / CI]. Normal range for RVSWI is 5-10 g/m.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic Vascular Resistance (SVR)</measure>
    <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
    <description>Systemic Vascular Resistance (SVR) was measured as mean of Systemic Vascular Resistance (SVR) for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for SVR is 800-1200 dynes/sec/cm5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central Venous Pressure (CVP)</measure>
    <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
    <description>Central Venous Pressure (CVP) was measured as mean of CVP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for CVP is 3-8 mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Arterial Pressure (MAP)</measure>
    <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
    <description>Mean Arterial Pressure (MAP) was measured as mean of MAP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for MAP is 70-110 mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
    <description>Heart Rate was measured as mean of Heart Rate for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for heart rate is generally 60 to 100 beats per minutes in adults, but this can vary.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Combined nitric oxide and prostacyclin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitric Oxide</intervention_name>
    <description>inhaled nitric oxide</description>
    <arm_group_label>Combined nitric oxide and prostacyclin</arm_group_label>
    <other_name>INOmax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prostacyclin</intervention_name>
    <description>inhaled prostacyclin</description>
    <arm_group_label>Combined nitric oxide and prostacyclin</arm_group_label>
    <other_name>inhaled flolan</other_name>
    <other_name>epoprostenol</other_name>
    <other_name>inhaled PGI2</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult cardiac surgical patients scheduled to undergo either heart transplantation or&#xD;
             LVAD placement&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with prior documented allergic reactions or intolerance to either nitric&#xD;
             oxide or prostacyclin will be excluded. Patients not undergoing heart transplantation&#xD;
             or LVAD placement will be excluded.&#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>Andrew J Powers, MD</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <location>
    <facility>
      <name>Stanford Hospital and Clinics</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Khan TA, Schnickel G, Ross D, Bastani S, Laks H, Esmailian F, Marelli D, Beygui R, Shemin R, Watson L, Vartapetian I, Ardehali A. A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. J Thorac Cardiovasc Surg. 2009 Dec;138(6):1417-24. doi: 10.1016/j.jtcvs.2009.04.063.</citation>
    <PMID>19931670</PMID>
  </reference>
  <reference>
    <citation>De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg. 2004 Apr;127(4):1058-67. doi: 10.1016/j.jtcvs.2003.11.035.</citation>
    <PMID>15052203</PMID>
  </reference>
  <reference>
    <citation>Potapov E, Meyer D, Swaminathan M, Ramsay M, El Banayosy A, Diehl C, Veynovich B, Gregoric ID, Kukucka M, Gromann TW, Marczin N, Chittuluru K, Baldassarre JS, Zucker MJ, Hetzer R. Inhaled nitric oxide after left ventricular assist device implantation: a prospective, randomized, double-blind, multicenter, placebo-controlled trial. J Heart Lung Transplant. 2011 Aug;30(8):870-8. doi: 10.1016/j.healun.2011.03.005. Epub 2011 Apr 29.</citation>
    <PMID>21530317</PMID>
  </reference>
  <reference>
    <citation>Antoniou T, Prokakis C, Athanasopoulos G, Thanopoulos A, Rellia P, Zarkalis D, Kogerakis N, Koletsis EN, Bairaktaris A. Inhaled nitric oxide plus iloprost in the setting of post-left assist device right heart dysfunction. Ann Thorac Surg. 2012 Sep;94(3):792-8. doi: 10.1016/j.athoracsur.2012.04.046. Epub 2012 Jun 23.</citation>
    <PMID>22727248</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <results_first_submitted>August 29, 2017</results_first_submitted>
  <results_first_submitted_qc>October 5, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 9, 2017</results_first_posted>
  <last_update_submitted>October 5, 2017</last_update_submitted>
  <last_update_submitted_qc>October 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Charles Hill</investigator_full_name>
    <investigator_title>Clinical Associate Professor</investigator_title>
  </responsible_party>
  <keyword>heart failure</keyword>
  <keyword>hypertension, pulmonary</keyword>
  <keyword>heart failure, right-sided</keyword>
  <keyword>heart-assist devices</keyword>
  <keyword>Heart Transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epoprostenol</mesh_term>
    <mesh_term>Nitric Oxide</mesh_term>
    <mesh_term>Tezosentan</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Combined Nitric Oxide and Prostacyclin</title>
          <description>Inhaled nitric oxide (iNO; 20 ppm continuously) and inhaled prostacyclin (iPGI2; 0.05 micrograms/kg/min continuously)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </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>Combined Nitric Oxide and Prostacyclin</title>
          <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57" lower_limit="29" upper_limit="68"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pulmonary Hypertension</title>
        <description>Pulmonary hypertension was measured as mean of Mean Pulmonary Artery Pressure for initial 8 hours after admission to the Intensive Care Unit (ICU). MPAP value ≥25 mmHg (resting) indicates pulmonary hypertension state.</description>
        <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Nitric Oxide and Prostacyclin</title>
            <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
          </group>
        </group_list>
        <measure>
          <title>Pulmonary Hypertension</title>
          <description>Pulmonary hypertension was measured as mean of Mean Pulmonary Artery Pressure for initial 8 hours after admission to the Intensive Care Unit (ICU). MPAP value ≥25 mmHg (resting) indicates pulmonary hypertension state.</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Arrival in ICU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.4" lower_limit="20" upper_limit="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.1" lower_limit="16" upper_limit="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (1st)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.9" lower_limit="17" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iPGI2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.4" lower_limit="15" upper_limit="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (2nd)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.4" lower_limit="12" upper_limit="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Right Heart Dysfunction</title>
        <description>Right Heart Dysfunction was measured as mean of Right Ventricular Stroke Work Index (RVSWI) for the initial 8 hours after admission to the Intensive Care Unit (ICU). RVSWI is measured as the difference in mean pulmonary artery pressure (MPAP) and central venous pressure (CVP), divided by the cardiac index (CI): [(MPAP-CVP) / CI]. Normal range for RVSWI is 5-10 g/m.</description>
        <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Nitric Oxide and Prostacyclin</title>
            <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
          </group>
        </group_list>
        <measure>
          <title>Right Heart Dysfunction</title>
          <description>Right Heart Dysfunction was measured as mean of Right Ventricular Stroke Work Index (RVSWI) for the initial 8 hours after admission to the Intensive Care Unit (ICU). RVSWI is measured as the difference in mean pulmonary artery pressure (MPAP) and central venous pressure (CVP), divided by the cardiac index (CI): [(MPAP-CVP) / CI]. Normal range for RVSWI is 5-10 g/m.</description>
          <units>g/m</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Arrival in ICU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" lower_limit="2.64" upper_limit="11.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" lower_limit="1.45" upper_limit="9.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (1st)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" lower_limit="1.96" upper_limit="8.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iPGI2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" lower_limit="2.10" upper_limit="13.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (2nd)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" lower_limit="1.30" upper_limit="10.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systemic Vascular Resistance (SVR)</title>
        <description>Systemic Vascular Resistance (SVR) was measured as mean of Systemic Vascular Resistance (SVR) for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for SVR is 800-1200 dynes/sec/cm5.</description>
        <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Nitric Oxide and Prostacyclin</title>
            <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
          </group>
        </group_list>
        <measure>
          <title>Systemic Vascular Resistance (SVR)</title>
          <description>Systemic Vascular Resistance (SVR) was measured as mean of Systemic Vascular Resistance (SVR) for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for SVR is 800-1200 dynes/sec/cm5.</description>
          <units>dynes/sec/cm^5</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Arrival in ICU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1193.9" lower_limit="488.0" upper_limit="1542"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1169.7" lower_limit="898.0" upper_limit="1945"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (1st)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1070.6" lower_limit="736.0" upper_limit="1520"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iPGI2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1132.4" lower_limit="711.00" upper_limit="1640"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (2nd)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1145.9" lower_limit="783.0" upper_limit="1649"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Central Venous Pressure (CVP)</title>
        <description>Central Venous Pressure (CVP) was measured as mean of CVP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for CVP is 3-8 mmHg.</description>
        <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Nitric Oxide and Prostacyclin</title>
            <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
          </group>
        </group_list>
        <measure>
          <title>Central Venous Pressure (CVP)</title>
          <description>Central Venous Pressure (CVP) was measured as mean of CVP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for CVP is 3-8 mmHg.</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Arrival in ICU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" lower_limit="4" upper_limit="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" lower_limit="5" upper_limit="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (1st)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" lower_limit="6" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iPGI2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.1" lower_limit="2" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (2nd)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6" lower_limit="4" upper_limit="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Arterial Pressure (MAP)</title>
        <description>Mean Arterial Pressure (MAP) was measured as mean of MAP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for MAP is 70-110 mmHg.</description>
        <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Nitric Oxide and Prostacyclin</title>
            <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Arterial Pressure (MAP)</title>
          <description>Mean Arterial Pressure (MAP) was measured as mean of MAP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for MAP is 70-110 mmHg.</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Arrival in ICU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.29" lower_limit="68" upper_limit="102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.86" lower_limit="62" upper_limit="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (1st)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.00" lower_limit="67" upper_limit="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iPGI2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.43" lower_limit="63" upper_limit="91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (2nd)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.86" lower_limit="61" upper_limit="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Heart Rate</title>
        <description>Heart Rate was measured as mean of Heart Rate for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for heart rate is generally 60 to 100 beats per minutes in adults, but this can vary.</description>
        <time_frame>8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Nitric Oxide and Prostacyclin</title>
            <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate</title>
          <description>Heart Rate was measured as mean of Heart Rate for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for heart rate is generally 60 to 100 beats per minutes in adults, but this can vary.</description>
          <units>beats/minute</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Arrival in ICU</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.1" lower_limit="75" upper_limit="152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112.5" lower_limit="71" upper_limit="166"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (1st)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.4" lower_limit="73" upper_limit="161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iPGI2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.0" lower_limit="67" upper_limit="134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Following iNO+iPGI2 (2nd)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.6" lower_limit="73" upper_limit="119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Combined Nitric Oxide and Prostacyclin</title>
          <description>iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)</description>
        </group>
      </group_list>
      <serious_events>
        <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="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
              </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>
    <limitations_and_caveats>Analyses are underpowered due low enrollment.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Charles Hill</name_or_title>
      <organization>Stanford University</organization>
      <phone>(650) 725-1930</phone>
      <email>chill1@stanford.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/NCT01717209
org study id: 25471
nct id: NCT01717209
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Research study evaluating the individual and combined effects of inhaled nitric oxide (iNO)
      and inhaled prostacyclin (iPGI2), on the function of the right heart after surgery for either
      heart transplant or for left ventricular assist device (LVAD) placement. The investigators
      hope to learn if these two medications, when given together after surgery, improve right
      heart function by lowering blood vessel pressures in the lungs. The investigators hope to
      learn if the combined effects of these two medications are better than either medication used
      alone. Participants were selected as a possible participant in this study because right heart
      problems are common during and after surgery for heart transplant and for LVAD placement. In
      addition, iNO is always given during and after these two types of surgeries at Stanford to
      help improve how the right heart functions.
The study will begin once the participant arrives in the cardiothoracic intensive care unit
      (CTICU) after heart surgery for either heart transplant or LVAD placement. As is standard of
      care after these types of surgeries, the participant will arrive in the CTICU with a
      breathing tube already in place, receiving iNO, and connected to a breathing machine. The
      participant will be receiving relaxing medication in an intravenous line provided by the
      cardiac anesthesiologist and the CTICU physicians. The participant will be unaware of the
      study period while the participant is sedated. Data will be collected from the monitor screen
      connected to the participant's arterial and venous lines, and if placed, LVAD monitor. These
      data are:

      Central venous pressure (CVP) Mean arterial pressure (MAP) Mean pulmonary artery pressure
      (MPAP) Cardiac Index (CI) Systemic vascular resistance (SVR) Pulmonary vascular resistance
      (PVR) Right ventricular stroke work index (RVSWI) LVAD Flow LVAD Pulsatility Index (PI)

      These data will be collected at five different time periods during the first eight hours
      after surgery.

        1. Time zero. Data will be collected after surgery upon your arrival to the CTICU while
           receiving iNO.

        2. After two hours of iNO treatment data will be collected. iPGI2 will then be combined
           with the current iNO.

        3. After two hours of combined iNO and iPGI2 treatment, data will be collected. iNO will
           then be stopped.

        4. After two hours of iPGI2 treatment data will be collected. iNO will be restarted.

        5. After two hours of combined iNO and iPGI2 treatment, data will be collected. The study
           ends after this data collection time.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pulmonary Hypertension
time frame: 8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))
description: Pulmonary hypertension was measured as mean of Mean Pulmonary Artery Pressure for initial 8 hours after admission to the Intensive Care Unit (ICU). MPAP value ≥25 mmHg (resting) indicates pulmonary hypertension state.
measure: Right Heart Dysfunction
time frame: 8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))
description: Right Heart Dysfunction was measured as mean of Right Ventricular Stroke Work Index (RVSWI) for the initial 8 hours after admission to the Intensive Care Unit (ICU). RVSWI is measured as the difference in mean pulmonary artery pressure (MPAP) and central venous pressure (CVP), divided by the cardiac index (CI): [(MPAP-CVP) / CI]. Normal range for RVSWI is 5-10 g/m.
measure: Systemic Vascular Resistance (SVR)
time frame: 8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))
description: Systemic Vascular Resistance (SVR) was measured as mean of Systemic Vascular Resistance (SVR) for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for SVR is 800-1200 dynes/sec/cm5.
measure: Central Venous Pressure (CVP)
time frame: 8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))
description: Central Venous Pressure (CVP) was measured as mean of CVP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for CVP is 3-8 mmHg.
measure: Mean Arterial Pressure (MAP)
time frame: 8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))
description: Mean Arterial Pressure (MAP) was measured as mean of MAP for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for MAP is 70-110 mmHg.
measure: Heart Rate
time frame: 8 hours (upon arrival at ICU, and after 4 successive 2 hour treatments with 1. iNO only, 2. iNO+iPGI2 (1st), 3. iPGI2 only, and 4. iNO+iPGI2 (2nd))
description: Heart Rate was measured as mean of Heart Rate for the initial 8 hours after admission to the Intensive Care Unit (ICU). Normal range for heart rate is generally 60 to 100 beats per minutes in adults, but this can vary.
arm group label: Combined nitric oxide and prostacyclin
arm group type: Experimental
description: iNO (20 ppm continuously) and iPGI2 (0.05 micrograms/kg/min continuously)
intervention type: Drug
intervention name: Nitric Oxide
description: inhaled nitric oxide
arm group label: Combined nitric oxide and prostacyclin
other name: INOmax
intervention type: Drug
intervention name: Prostacyclin
description: inhaled prostacyclin
arm group label: Combined nitric oxide and prostacyclin
other name: inhaled flolan
other name: epoprostenol
other name: inhaled PGI2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew J Powers, MD
role: Principal Investigator
facility: 
country: United States
citation: Khan TA, Schnickel G, Ross D, Bastani S, Laks H, Esmailian F, Marelli D, Beygui R, Shemin R, Watson L, Vartapetian I, Ardehali A. A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. J Thorac Cardiovasc Surg. 2009 Dec;138(6):1417-24. doi: 10.1016/j.jtcvs.2009.04.063.
PMID: 19931670
citation: De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg. 2004 Apr;127(4):1058-67. doi: 10.1016/j.jtcvs.2003.11.035.
PMID: 15052203
citation: Potapov E, Meyer D, Swaminathan M, Ramsay M, El Banayosy A, Diehl C, Veynovich B, Gregoric ID, Kukucka M, Gromann TW, Marczin N, Chittuluru K, Baldassarre JS, Zucker MJ, Hetzer R. Inhaled nitric oxide after left ventricular assist device implantation: a prospective, randomized, double-blind, multicenter, placebo-controlled trial. J Heart Lung Transplant. 2011 Aug;30(8):870-8. doi: 10.1016/j.healun.2011.03.005. Epub 2011 Apr 29.
PMID: 21530317
citation: Antoniou T, Prokakis C, Athanasopoulos G, Thanopoulos A, Rellia P, Zarkalis D, Kogerakis N, Koletsis EN, Bairaktaris A. Inhaled nitric oxide plus iloprost in the setting of post-left assist device right heart dysfunction. Ann Thorac Surg. 2012 Sep;94(3):792-8. doi: 10.1016/j.athoracsur.2012.04.046. Epub 2012 Jun 23.
PMID: 22727248
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Charles Hill
investigator title: Clinical Associate Professor
mesh term: Heart Failure
mesh term: Epoprostenol
mesh term: Nitric Oxide
mesh term: Tezosentan
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Analyses are underpowered due low enrollment.
point of contact: 