<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/NCT01715883</url>
  </required_header>
  <id_info>
    <org_study_id>PRO11030251</org_study_id>
    <nct_id>NCT01715883</nct_id>
  </id_info>
  <brief_title>Sodium Nitrite in Lung Transplant Patients to Minimize the Risk of Pulmonary Graft Dysfunction</brief_title>
  <official_title>Sodium Nitrite Administration at the Time of Lung Organ Procurement and Transplantation to Minimize the Risk of Pulmonary Graft Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gladwin, Mark, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2 observational nonrandomized pilot investigation to evaluate the safety and&#xD;
      efficacy of Sodium Nitrite administration for the reduction of Primary Graft Dysfunction&#xD;
      (PGD) in patients undergoing lung transplant. The study will enroll 8 subjects, undergoing&#xD;
      lung transplant at the University of Pittsburgh Medical Center (UPMC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      While increasing numbers of patients with advanced lung disease are candidates for lung&#xD;
      transplantation, the short- and long-term outcomes are severely compromised by graft&#xD;
      dysfunction, primarily in the form of organ rejection. The earliest manifestation of lung&#xD;
      allograft dysfunction, termed primary graft dysfunction (PGD), represents a form of&#xD;
      ischemia-reperfusion acute lung injury, and occurs in its severest form (Grade 3) in from 10&#xD;
      to 35% of lung transplant recipients 1-6. PGD is the primary cause of early morbidity and&#xD;
      mortality after transplantation and is strongly associated with the late development of&#xD;
      chronic lung rejection or Bronchiolitis Obliterans Syndrome (BOS. Early graft dysfunction&#xD;
      contributes significantly to the suboptimal outcomes of lung transplantation and to the&#xD;
      failure of lung transplant recipients to achieve five-year survival rates comparable to&#xD;
      patients who receive other solid organs such as the heart and liver. The risk of PGD further&#xD;
      limits the time that lungs can be stored ex-vivo, therefore restricting the pool of available&#xD;
      donors. A critical advance in the prevention of both early and late lung allograft&#xD;
      dysfunction will occur if PGD can be successfully prevented or minimized.&#xD;
&#xD;
      In this study, the investigators propose to test the hypothesis that administration of Sodium&#xD;
      Nitrite to donor lungs and lung transplant recipients at the time of transplantation will be&#xD;
      safe and will reduce the incidence of grades 2 and 3 PGD, thereby improving clinical outcomes&#xD;
      with minimal toxicity.&#xD;
&#xD;
      Sodium Nitrite will be obtained from a commercial preparation (Hope Pharmaceuticals) and the&#xD;
      UPMC Pharmacy will prepare the formulations, which will be infused at three time points.&#xD;
      First it will be infused into the preservation solution bag at the time of organ procurement&#xD;
      from the donor, then to the allograft at the time of transplantation, and finally as a direct&#xD;
      infusion into the organ recipient.&#xD;
&#xD;
      The investigators plan to enroll total of 8 subjects undergoing lung transplantation for this&#xD;
      Phase 2 observational non-randomized pilot investigation to evaluate the safety, efficacy,&#xD;
      and pharmacokinetics of Sodium Nitrite administration when administered to the procured lung&#xD;
      and lung transplant recipient, for the prevention of Primary Graft Dysfunction (PGD). It is&#xD;
      anticipated that positive results from this trial lead to a larger clinical investigation of&#xD;
      Sodium Nitrite administration directed at producing a reduction in PGD and perhaps secondary&#xD;
      obliterative bronchiolitis; and will potentially allow for extended organ storage, extended&#xD;
      use of more marginal organs, and more effective use of Donation after Cardiac Death (DCD)&#xD;
      organs which undergo combination of warm and cold ischemia for organ procurement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of support staff&#xD;
  </why_stopped>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of Sodium Nitrite Administration Measured by Methemoglobin Levels</measure>
    <time_frame>150 minutes post infusion</time_frame>
    <description>The safety of Sodium Nitrite administration will be assessed by methemoglobin levels during and 150 minutes after the nitrite infusion in the transplant recipient.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety of Sodium Nitrite Administration - Number of Participants With Fall in Patient's Mean Arterial Pressure Greater Than 20%</measure>
    <time_frame>Baseline and 1 hour post infusion</time_frame>
    <description>The safety of Sodium Nitrite administration will be assessed by the incidence of fall in patient's Mean Arterial Pressure greater than 20% from recorded baseline requiring discontinuation of drug infusion during and after the nitrite infusion in the transplant recipient. Mean Arterial Pressure will be monitored at 1 minute intervals during study drug infusion followed by 15 minute intervals for 1 hour.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Primary Graft Dysfunction Grades 2+3</measure>
    <time_frame>First 72 hours post organ reperfusion.</time_frame>
    <description>The primary study endpoint is the incidence of grades 2+3 Primary Graft Dysfunction (PGD) based upon the worst PGD grade during the first 72 hours post organ reperfusion. The severity of PGD is graded 0-3 based on the presence or absence of diffuse opacities on chest radiograph and the ratio of arterial oxygen pressure to inspired oxygen concentration. The grading system predicts post-lung transplant outcomes with Grade 3 being the worst.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Acute Rejection</measure>
    <time_frame>Up to 12 months post lung transplant</time_frame>
    <description>To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of acute rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Chronic Rejection</measure>
    <time_frame>Up to 12 months post lung transplant</time_frame>
    <description>To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of chronic rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Ventilator Free Days (VFD)</measure>
    <time_frame>Baseline through Day 30 post transplantation.</time_frame>
    <description>Defined as the number of days off mechanical ventilation at baseline through Day 30 post transplantation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of ICU Free Days (IFD)</measure>
    <time_frame>Day 30 post transplantation.</time_frame>
    <description>Defined as the number of days outside the ICU through Day 30 post transplantation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Primary Graft Dysfunction</condition>
  <arm_group>
    <arm_group_label>Sodium Nitrite</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8 liter bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the portal vein (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Nitrite</intervention_name>
    <description>Same as the details in Arm Description.</description>
    <arm_group_label>Sodium Nitrite</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects undergoing lung transplantation.&#xD;
&#xD;
          -  Subjects in the age range of 18-70 years&#xD;
&#xD;
          -  Ability to understand and provide consent. Proxy consent will not be accepted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Donor exclusion criteria&#xD;
&#xD;
          -  Age &gt; 55 years.&#xD;
&#xD;
          -  Mechanical ventilation &gt; 5 days prior to procurement&#xD;
&#xD;
          -  Significant chest trauma or lung contusion&#xD;
&#xD;
          -  Smoking history &gt; 20 pack-year&#xD;
&#xD;
          -  Ratio of arterial oxygen partial pressure to fractional inspired oxygen &lt; 300&#xD;
&#xD;
          -  Donor radiograph with 2 quadrant infiltrates&#xD;
&#xD;
          -  Donor that are determined single lung donors prior to transplant will be excluded.&#xD;
&#xD;
        Recipient exclusion criteria&#xD;
&#xD;
          -  Recipient age &gt; 70 years.&#xD;
&#xD;
          -  Recipient history of pulmonary hypertension (idiopathic pulmonary arterial&#xD;
             hypertension, or secondary pulmonary arterial hypertension with mean arterial pressure&#xD;
             &gt; 30 mm Hg)&#xD;
&#xD;
          -  Recipient history of abnormal cardiac function defined as prior coronary artery bypass&#xD;
             graft (CABG) or left ventricular ejection fraction (LVEF) &lt; 45 %&#xD;
&#xD;
          -  Recipient history of open thoracotomy/prior pleurodesis as exclusion criteria. However&#xD;
             patients who have had limited video-assisted thoracic surgery procedures for biopsies&#xD;
             would NOT be excluded from the study.&#xD;
&#xD;
          -  Recipient history of cirrhosis&#xD;
&#xD;
          -  Recipient history of mechanical ventilation or extracorporeal support pre-operatively&#xD;
&#xD;
          -  Recipient pre-operative hypotension defined by a systolic blood pressure less than 90&#xD;
             mm Hg not responsive to intravenous fluids or requirement for vasoactive medications&#xD;
&#xD;
          -  Recipient preoperative history of renal insufficiency, dialysis or estimated&#xD;
             glomerular filtration rate &lt;30 ml/min/1.73 m2 body surface area&#xD;
&#xD;
          -  Patients undergoing retransplantation&#xD;
&#xD;
          -  Recipient history of significant coronary artery disease that is flow limiting and&#xD;
             unable to be corrected by further percutaneous coronary artery interventions.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew Morrell, MD</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>
  <reference>
    <citation>Bobadilla JL, Love RB, Jankowska-Gan E, Xu Q, Haynes LD, Braun RK, Hayney MS, Munoz del Rio A, Meyer K, Greenspan DS, Torrealba J, Heidler KM, Cummings OW, Iwata T, Brand D, Presson R, Burlingham WJ, Wilkes DS. Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med. 2008 Mar 15;177(6):660-8. doi: 10.1164/rccm.200612-1901OC. Epub 2008 Jan 3.</citation>
    <PMID>18174545</PMID>
  </reference>
  <reference>
    <citation>Christie JD, Van Raemdonck D, de Perrot M, Barr M, Keshavjee S, Arcasoy S, Orens J; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part I: introduction and methods. J Heart Lung Transplant. 2005 Oct;24(10):1451-3. doi: 10.1016/j.healun.2005.03.004. No abstract available.</citation>
    <PMID>16210115</PMID>
  </reference>
  <reference>
    <citation>Huang HJ, Yusen RD, Meyers BF, Walter MJ, Mohanakumar T, Patterson GA, Trulock EP, Hachem RR. Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome. Am J Transplant. 2008 Nov;8(11):2454-62. doi: 10.1111/j.1600-6143.2008.02389.x. Epub 2008 Sep 10.</citation>
    <PMID>18785961</PMID>
  </reference>
  <reference>
    <citation>Kuntz CL, Hadjiliadis D, Ahya VN, Kotloff RM, Pochettino A, Lewis J, Christie JD. Risk factors for early primary graft dysfunction after lung transplantation: a registry study. Clin Transplant. 2009 Nov-Dec;23(6):819-30. doi: 10.1111/j.1399-0012.2008.00951.x. Epub 2009 Feb 20.</citation>
    <PMID>19239481</PMID>
  </reference>
  <reference>
    <citation>Prekker ME, Nath DS, Walker AR, Johnson AC, Hertz MI, Herrington CS, Radosevich DM, Dahlberg PS. Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation. J Heart Lung Transplant. 2006 Apr;25(4):371-8. doi: 10.1016/j.healun.2005.11.436. Epub 2006 Feb 28.</citation>
    <PMID>16563963</PMID>
  </reference>
  <reference>
    <citation>Lee JC, Christie JD. Primary graft dysfunction. Proc Am Thorac Soc. 2009 Jan 15;6(1):39-46. doi: 10.1513/pats.200808-082GO.</citation>
    <PMID>19131529</PMID>
  </reference>
  <reference>
    <citation>Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005 Oct;24(10):1454-9. doi: 10.1016/j.healun.2004.11.049. Epub 2005 Jun 4. No abstract available.</citation>
    <PMID>16210116</PMID>
  </reference>
  <reference>
    <citation>de Perrot M, Bonser RS, Dark J, Kelly RF, McGiffin D, Menza R, Pajaro O, Schueler S, Verleden GM; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005 Oct;24(10):1460-7. doi: 10.1016/j.healun.2005.02.017. Epub 2005 Aug 8. No abstract available.</citation>
    <PMID>16210117</PMID>
  </reference>
  <reference>
    <citation>Thabut G, Vinatier I, Stern JB, Leseche G, Loirat P, Fournier M, Mal H. Primary graft failure following lung transplantation: predictive factors of mortality. Chest. 2002 Jun;121(6):1876-82. doi: 10.1378/chest.121.6.1876.</citation>
    <PMID>12065352</PMID>
  </reference>
  <reference>
    <citation>Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO 3rd, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007 Oct 16;116(16):1821-31. doi: 10.1161/CIRCULATIONAHA.107.712133. Epub 2007 Sep 24.</citation>
    <PMID>17893272</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <results_first_submitted>May 31, 2018</results_first_submitted>
  <results_first_submitted_qc>July 5, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 1, 2018</results_first_posted>
  <last_update_submitted>July 5, 2018</last_update_submitted>
  <last_update_submitted_qc>July 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Matthew Morrell</investigator_full_name>
    <investigator_title>Assistant Professor, Department of Medicine, Division of Pulmonary, Allergy and Critical care medicine</investigator_title>
  </responsible_party>
  <keyword>Lung transplant</keyword>
  <keyword>Pulmonary Graft Dysfunction</keyword>
  <keyword>Sodium Nitrite</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primary Graft Dysfunction</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 3, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT01715883/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sodium Nitrite</title>
          <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8 Liter bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the portal vein (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sodium Nitrite</title>
          <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8 Liter bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the portal vein (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety of Sodium Nitrite Administration Measured by Methemoglobin Levels</title>
        <description>The safety of Sodium Nitrite administration will be assessed by methemoglobin levels during and 150 minutes after the nitrite infusion in the transplant recipient.</description>
        <time_frame>150 minutes post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety of Sodium Nitrite Administration Measured by Methemoglobin Levels</title>
          <description>The safety of Sodium Nitrite administration will be assessed by methemoglobin levels during and 150 minutes after the nitrite infusion in the transplant recipient.</description>
          <units>percentage of methemoglobin</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.45" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety of Sodium Nitrite Administration - Number of Participants With Fall in Patient's Mean Arterial Pressure Greater Than 20%</title>
        <description>The safety of Sodium Nitrite administration will be assessed by the incidence of fall in patient's Mean Arterial Pressure greater than 20% from recorded baseline requiring discontinuation of drug infusion during and after the nitrite infusion in the transplant recipient. Mean Arterial Pressure will be monitored at 1 minute intervals during study drug infusion followed by 15 minute intervals for 1 hour.</description>
        <time_frame>Baseline and 1 hour post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety of Sodium Nitrite Administration - Number of Participants With Fall in Patient's Mean Arterial Pressure Greater Than 20%</title>
          <description>The safety of Sodium Nitrite administration will be assessed by the incidence of fall in patient's Mean Arterial Pressure greater than 20% from recorded baseline requiring discontinuation of drug infusion during and after the nitrite infusion in the transplant recipient. Mean Arterial Pressure will be monitored at 1 minute intervals during study drug infusion followed by 15 minute intervals for 1 hour.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Primary Graft Dysfunction Grades 2+3</title>
        <description>The primary study endpoint is the incidence of grades 2+3 Primary Graft Dysfunction (PGD) based upon the worst PGD grade during the first 72 hours post organ reperfusion. The severity of PGD is graded 0-3 based on the presence or absence of diffuse opacities on chest radiograph and the ratio of arterial oxygen pressure to inspired oxygen concentration. The grading system predicts post-lung transplant outcomes with Grade 3 being the worst.</description>
        <time_frame>First 72 hours post organ reperfusion.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Primary Graft Dysfunction Grades 2+3</title>
          <description>The primary study endpoint is the incidence of grades 2+3 Primary Graft Dysfunction (PGD) based upon the worst PGD grade during the first 72 hours post organ reperfusion. The severity of PGD is graded 0-3 based on the presence or absence of diffuse opacities on chest radiograph and the ratio of arterial oxygen pressure to inspired oxygen concentration. The grading system predicts post-lung transplant outcomes with Grade 3 being the worst.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Acute Rejection</title>
        <description>To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of acute rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.</description>
        <time_frame>Up to 12 months post lung transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Acute Rejection</title>
          <description>To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of acute rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Chronic Rejection</title>
        <description>To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of chronic rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.</description>
        <time_frame>Up to 12 months post lung transplant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Chronic Rejection</title>
          <description>To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of chronic rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Ventilator Free Days (VFD)</title>
        <description>Defined as the number of days off mechanical ventilation at baseline through Day 30 post transplantation.</description>
        <time_frame>Baseline through Day 30 post transplantation.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Ventilator Free Days (VFD)</title>
          <description>Defined as the number of days off mechanical ventilation at baseline through Day 30 post transplantation.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" spread="15.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of ICU Free Days (IFD)</title>
        <description>Defined as the number of days outside the ICU through Day 30 post transplantation.</description>
        <time_frame>Day 30 post transplantation.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sodium Nitrite</title>
            <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of ICU Free Days (IFD)</title>
          <description>Defined as the number of days outside the ICU through Day 30 post transplantation.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.7" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From study enrollment to 72 hours after the last dose of study drug, an average of 1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sodium Nitrite</title>
          <description>Sodium Nitrite will be administered at three time points:&#xD;
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs.&#xD;
At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.&#xD;
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.&#xD;
Sodium Nitrite: Same as the details in Arm Description.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atypical appearance of the lungs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </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>The clinical trial was terminated early due to lack of funding support, difficulty in recruiting patients and lack of support staff. Early termination leading to small numbers of subjects analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Matthew Morrell, MD</name_or_title>
      <organization>University of Pittsburgh</organization>
      <phone>412-647-8477</phone>
      <email>morrellmr@upmc.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/NCT01715883
org study id: PRO11030251
nct id: NCT01715883
lead sponsor: 
has dmc: Yes
This is a Phase 2 observational nonrandomized pilot investigation to evaluate the safety and
      efficacy of Sodium Nitrite administration for the reduction of Primary Graft Dysfunction
      (PGD) in patients undergoing lung transplant. The study will enroll 8 subjects, undergoing
      lung transplant at the University of Pittsburgh Medical Center (UPMC).
While increasing numbers of patients with advanced lung disease are candidates for lung
      transplantation, the short- and long-term outcomes are severely compromised by graft
      dysfunction, primarily in the form of organ rejection. The earliest manifestation of lung
      allograft dysfunction, termed primary graft dysfunction (PGD), represents a form of
      ischemia-reperfusion acute lung injury, and occurs in its severest form (Grade 3) in from 10
      to 35% of lung transplant recipients 1-6. PGD is the primary cause of early morbidity and
      mortality after transplantation and is strongly associated with the late development of
      chronic lung rejection or Bronchiolitis Obliterans Syndrome (BOS. Early graft dysfunction
      contributes significantly to the suboptimal outcomes of lung transplantation and to the
      failure of lung transplant recipients to achieve five-year survival rates comparable to
      patients who receive other solid organs such as the heart and liver. The risk of PGD further
      limits the time that lungs can be stored ex-vivo, therefore restricting the pool of available
      donors. A critical advance in the prevention of both early and late lung allograft
      dysfunction will occur if PGD can be successfully prevented or minimized.

      In this study, the investigators propose to test the hypothesis that administration of Sodium
      Nitrite to donor lungs and lung transplant recipients at the time of transplantation will be
      safe and will reduce the incidence of grades 2 and 3 PGD, thereby improving clinical outcomes
      with minimal toxicity.

      Sodium Nitrite will be obtained from a commercial preparation (Hope Pharmaceuticals) and the
      UPMC Pharmacy will prepare the formulations, which will be infused at three time points.
      First it will be infused into the preservation solution bag at the time of organ procurement
      from the donor, then to the allograft at the time of transplantation, and finally as a direct
      infusion into the organ recipient.

      The investigators plan to enroll total of 8 subjects undergoing lung transplantation for this
      Phase 2 observational non-randomized pilot investigation to evaluate the safety, efficacy,
      and pharmacokinetics of Sodium Nitrite administration when administered to the procured lung
      and lung transplant recipient, for the prevention of Primary Graft Dysfunction (PGD). It is
      anticipated that positive results from this trial lead to a larger clinical investigation of
      Sodium Nitrite administration directed at producing a reduction in PGD and perhaps secondary
      obliterative bronchiolitis; and will potentially allow for extended organ storage, extended
      use of more marginal organs, and more effective use of Donation after Cardiac Death (DCD)
      organs which undergo combination of warm and cold ischemia for organ procurement.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Safety of Sodium Nitrite Administration Measured by Methemoglobin Levels
time frame: 150 minutes post infusion
description: The safety of Sodium Nitrite administration will be assessed by methemoglobin levels during and 150 minutes after the nitrite infusion in the transplant recipient.
measure: Safety of Sodium Nitrite Administration - Number of Participants With Fall in Patient's Mean Arterial Pressure Greater Than 20%
time frame: Baseline and 1 hour post infusion
description: The safety of Sodium Nitrite administration will be assessed by the incidence of fall in patient's Mean Arterial Pressure greater than 20% from recorded baseline requiring discontinuation of drug infusion during and after the nitrite infusion in the transplant recipient. Mean Arterial Pressure will be monitored at 1 minute intervals during study drug infusion followed by 15 minute intervals for 1 hour.
measure: Number of Participants With Primary Graft Dysfunction Grades 2+3
time frame: First 72 hours post organ reperfusion.
description: The primary study endpoint is the incidence of grades 2+3 Primary Graft Dysfunction (PGD) based upon the worst PGD grade during the first 72 hours post organ reperfusion. The severity of PGD is graded 0-3 based on the presence or absence of diffuse opacities on chest radiograph and the ratio of arterial oxygen pressure to inspired oxygen concentration. The grading system predicts post-lung transplant outcomes with Grade 3 being the worst.
measure: Number of Participants With Acute Rejection
time frame: Up to 12 months post lung transplant
description: To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of acute rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.
measure: Number of Participants With Chronic Rejection
time frame: Up to 12 months post lung transplant
description: To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of chronic rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.
measure: Number of Ventilator Free Days (VFD)
time frame: Baseline through Day 30 post transplantation.
description: Defined as the number of days off mechanical ventilation at baseline through Day 30 post transplantation.
measure: Number of ICU Free Days (IFD)
time frame: Day 30 post transplantation.
description: Defined as the number of days outside the ICU through Day 30 post transplantation.
arm group label: Sodium Nitrite
arm group type: Experimental
description: Sodium Nitrite will be administered at three time points:
At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8 liter bags of Perfadex solution to flush the donor lungs.
At the time of transplant just prior to reperfusion of lungs, the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the portal vein (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes.
Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min.
intervention type: Drug
intervention name: Sodium Nitrite
description: Same as the details in Arm Description.
arm group label: Sodium Nitrite
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Matthew Morrell, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
citation: Bobadilla JL, Love RB, Jankowska-Gan E, Xu Q, Haynes LD, Braun RK, Hayney MS, Munoz del Rio A, Meyer K, Greenspan DS, Torrealba J, Heidler KM, Cummings OW, Iwata T, Brand D, Presson R, Burlingham WJ, Wilkes DS. Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med. 2008 Mar 15;177(6):660-8. doi: 10.1164/rccm.200612-1901OC. Epub 2008 Jan 3.
PMID: 18174545
citation: Christie JD, Van Raemdonck D, de Perrot M, Barr M, Keshavjee S, Arcasoy S, Orens J; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part I: introduction and methods. J Heart Lung Transplant. 2005 Oct;24(10):1451-3. doi: 10.1016/j.healun.2005.03.004. No abstract available.
PMID: 16210115
citation: Huang HJ, Yusen RD, Meyers BF, Walter MJ, Mohanakumar T, Patterson GA, Trulock EP, Hachem RR. Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome. Am J Transplant. 2008 Nov;8(11):2454-62. doi: 10.1111/j.1600-6143.2008.02389.x. Epub 2008 Sep 10.
PMID: 18785961
citation: Kuntz CL, Hadjiliadis D, Ahya VN, Kotloff RM, Pochettino A, Lewis J, Christie JD. Risk factors for early primary graft dysfunction after lung transplantation: a registry study. Clin Transplant. 2009 Nov-Dec;23(6):819-30. doi: 10.1111/j.1399-0012.2008.00951.x. Epub 2009 Feb 20.
PMID: 19239481
citation: Prekker ME, Nath DS, Walker AR, Johnson AC, Hertz MI, Herrington CS, Radosevich DM, Dahlberg PS. Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation. J Heart Lung Transplant. 2006 Apr;25(4):371-8. doi: 10.1016/j.healun.2005.11.436. Epub 2006 Feb 28.
PMID: 16563963
citation: Lee JC, Christie JD. Primary graft dysfunction. Proc Am Thorac Soc. 2009 Jan 15;6(1):39-46. doi: 10.1513/pats.200808-082GO.
PMID: 19131529
citation: Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005 Oct;24(10):1454-9. doi: 10.1016/j.healun.2004.11.049. Epub 2005 Jun 4. No abstract available.
PMID: 16210116
citation: de Perrot M, Bonser RS, Dark J, Kelly RF, McGiffin D, Menza R, Pajaro O, Schueler S, Verleden GM; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005 Oct;24(10):1460-7. doi: 10.1016/j.healun.2005.02.017. Epub 2005 Aug 8. No abstract available.
PMID: 16210117
citation: Thabut G, Vinatier I, Stern JB, Leseche G, Loirat P, Fournier M, Mal H. Primary graft failure following lung transplantation: predictive factors of mortality. Chest. 2002 Jun;121(6):1876-82. doi: 10.1378/chest.121.6.1876.
PMID: 12065352
citation: Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO 3rd, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007 Oct 16;116(16):1821-31. doi: 10.1161/CIRCULATIONAHA.107.712133. Epub 2007 Sep 24.
PMID: 17893272
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Matthew Morrell
investigator title: Assistant Professor, Department of Medicine, Division of Pulmonary, Allergy and Critical care medicine
mesh term: Primary Graft Dysfunction
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The clinical trial was terminated early due to lack of funding support, difficulty in recruiting patients and lack of support staff. Early termination leading to small numbers of subjects analyzed.
point of contact: 