<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/NCT03009643</url>
  </required_header>
  <id_info>
    <org_study_id>STiNO</org_study_id>
    <nct_id>NCT03009643</nct_id>
  </id_info>
  <brief_title>Salvage Treatment of Inhaled Nitric Oxide in Patients With Refractory Hypoxemia After Aortic Surgery</brief_title>
  <official_title>Salvage Treatment of Inhaled Nitric Oxide in Patients With Refractory Hypoxemia After Aortic Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Zhongshan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Zhongshan Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypoxemia is a common complication after aortic surgery. As this complication has an adverse&#xD;
      effect on the postoperative course of the patient, early treatment is important; however, the&#xD;
      mechanism of hypoxemia after surgery for acute aortic dissection remains unclear. Recently,&#xD;
      the investigators found that inhaled Nitric Oxide can improve the oxygenation in some of&#xD;
      these patients. The investigators are trying to evaluate the effectiveness and safety of&#xD;
      inhaled Nitric Oxide in patients with refractory hypoxemia after aortic surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Several risk factors for severe hypoxemia after aortic surgery have been reported including&#xD;
      advanced age, obesity, smoking history, previous heart surgery,emergency surgery,reduced&#xD;
      cardiac function, advanced chronic obstructive pulmonary disease, excessive volume of blood&#xD;
      transfusion,and prolonged CPB time. The routine treatment includes lung protective mechanical&#xD;
      ventilation, recruitment maneuvers and glucocorticoids.&#xD;
&#xD;
      No previous clinical studies have reported the effectiveness and safety of inhaled Nitric&#xD;
      Oxide in patients with refractory hypoxemia after aortic surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mechanical ventilation time (days)</measure>
    <time_frame>During whole ICU stay. From date of randomization until the date of death or discharge from ICU, up to 6 months.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU mortality</measure>
    <time_frame>From date of randomization until the date of death or discharge from ICU, up to 6 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of hospital stay (days)</measure>
    <time_frame>From date of randomization until the date of death or discharge from hospital, up to 6 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of ICU stay (days)</measure>
    <time_frame>From date of randomization until the date of death or discharge from ICU, up to 6 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hospital mortality</measure>
    <time_frame>From date of randomization until the date of death or discharge from hospital, up to 6 months.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Nitric Oxide</condition>
  <condition>Hypoxemia</condition>
  <condition>Aortic Surgery</condition>
  <arm_group>
    <arm_group_label>iNO Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are treated with iNO at a concentration of 5-10 ppm for 3-5 days according to the clinical conditions</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients are treated without iNO.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled Nitric Oxide</intervention_name>
    <description>Patients are treated with iNO for 3-5 days.The concentration of inhaled Nitric Oxide is around 5-10ppm.</description>
    <arm_group_label>iNO Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>lung protective mechanical ventilation</intervention_name>
    <description>Mechanical ventilation in the SIMV mode (ventilators Evita 2 or 4,Dräger, Lübeck, Germany) with VT 6-8ml/kg</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>iNO Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Hemodynamic monitoring</intervention_name>
    <description>Flotrac/Vigileo (Edwards Lifesciences) are used to guide the fluid management.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>iNO Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients with refractory hypoxemia after aortic surgery;&#xD;
&#xD;
          2. Accepting invasive mechanical ventilation;&#xD;
&#xD;
          3. Chest X-ray and lung ultrasound to exclude the respiratory factors (eg. pulmonary&#xD;
             edema, obstructive atelectasis, pleural effusion, pneumothorax) and hemodynamic&#xD;
             factors (pericardial tamponade, acute pulmonary hypertension, intracardiac shunt);&#xD;
&#xD;
          4. The ventilator parameters: PEEP&gt;10cmH2O, VT 6-8ml/kg;&#xD;
&#xD;
          5. The PaO2/FiO2 &lt;= 100mmHg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt;18 years old;&#xD;
&#xD;
          2. Pregnant women;&#xD;
&#xD;
          3. Past medical history included COPD or mental illness;&#xD;
&#xD;
          4. The serious infection or sepsis patients;&#xD;
&#xD;
          5. Patients with pulmonary hypertension and right ventricular dysfunction&#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>Zhe Luo, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Critical Care Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Guo-wei Tu, MD</last_name>
    <phone>+8613501996995</phone>
    <email>tu.guowei@zs-hospital.sh.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Guo-guang Ma, MD</last_name>
    <phone>+8615021519979</phone>
    <email>ma.guoguang@zs-hospital.sh.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai Zhongshan Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guo-wei Tu, MD</last_name>
      <phone>+8613501996995</phone>
      <email>tu.guowei@zs-hospital.sh.cn</email>
    </contact>
    <contact_backup>
      <last_name>Zhe Luo, PhD</last_name>
      <phone>+13916127028</phone>
      <email>luo.zhe@zs-hospital.sh.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Guang-wei Hao, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Guo-guang Ma, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://link.springer.com/article/10.1007%2Fs00595-006-3226-5</url>
    <description>Springer</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649943/</url>
    <description>biomed central</description>
  </link>
  <link>
    <url>http://www.nature.com/nature/journal/v327/n6122/abs/327524a0.html</url>
    <description>Nature Publishing Group</description>
  </link>
  <reference>
    <citation>Garcia-Delgado M, Navarrete-Sanchez I, Colmenero M. Preventing and managing perioperative pulmonary complications following cardiac surgery. Curr Opin Anaesthesiol. 2014 Apr;27(2):146-52. doi: 10.1097/ACO.0000000000000059.</citation>
    <PMID>24514031</PMID>
  </reference>
  <reference>
    <citation>Ball L, Battaglini D, Pelosi P. Postoperative respiratory disorders. Curr Opin Crit Care. 2016 Aug;22(4):379-85. doi: 10.1097/MCC.0000000000000312.</citation>
    <PMID>27168252</PMID>
  </reference>
  <reference>
    <citation>Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. 2005 Dec 22;353(25):2683-95. doi: 10.1056/NEJMra051884. No abstract available.</citation>
    <PMID>16371634</PMID>
  </reference>
  <results_reference>
    <citation>Nakajima T, Kawazoe K, Izumoto H, Kataoka T, Niinuma H, Shirahashi N. Risk factors for hypoxemia after surgery for acute type A aortic dissection. Surg Today. 2006;36(8):680-5. doi: 10.1007/s00595-006-3226-5.</citation>
    <PMID>16865510</PMID>
  </results_reference>
  <results_reference>
    <citation>Wang Y, Xue S, Zhu H. Risk factors for postoperative hypoxemia in patients undergoing Stanford A aortic dissection surgery. J Cardiothorac Surg. 2013 Apr 30;8:118. doi: 10.1186/1749-8090-8-118.</citation>
    <PMID>23631417</PMID>
  </results_reference>
  <results_reference>
    <citation>Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6. doi: 10.1038/327524a0.</citation>
    <PMID>3495737</PMID>
  </results_reference>
  <results_reference>
    <citation>Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation. 1991 Jun;83(6):2038-47. doi: 10.1161/01.cir.83.6.2038. Erratum In: Circulation 1991 Nov;84(5):2212.</citation>
    <PMID>2040056</PMID>
  </results_reference>
  <results_reference>
    <citation>Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology. 1993 Mar;78(3):427-35. doi: 10.1097/00000542-199303000-00005.</citation>
    <PMID>8457043</PMID>
  </results_reference>
  <results_reference>
    <citation>Benedetto M, Romano R, Baca G, Sarridou D, Fischer A, Simon A, Marczin N. Inhaled nitric oxide in cardiac surgery: Evidence or tradition? Nitric Oxide. 2015 Sep 15;49:67-79. doi: 10.1016/j.niox.2015.06.002. Epub 2015 Jul 14.</citation>
    <PMID>26186889</PMID>
  </results_reference>
  <results_reference>
    <citation>Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, Roy BJ, Keszler M, Kinsella JP. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med. 2000 Feb 17;342(7):469-74. doi: 10.1056/NEJM200002173420704.</citation>
    <PMID>10675427</PMID>
  </results_reference>
  <results_reference>
    <citation>Cornfield DN, Maynard RC, deRegnier RA, Guiang SF 3rd, Barbato JE, Milla CE. Randomized, controlled trial of low-dose inhaled nitric oxide in the treatment of term and near-term infants with respiratory failure and pulmonary hypertension. Pediatrics. 1999 Nov;104(5 Pt 1):1089-94. doi: 10.1542/peds.104.5.1089.</citation>
    <PMID>10545552</PMID>
  </results_reference>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>December 26, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <last_update_submitted>February 1, 2018</last_update_submitted>
  <last_update_submitted_qc>February 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Zhongshan Hospital</investigator_affiliation>
    <investigator_full_name>Guowei Tu</investigator_full_name>
    <investigator_title>Attending doctor, Department of cardiac surgery intensive care unit, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Nitric Oxide</keyword>
  <keyword>hypoxemia</keyword>
  <keyword>aortic surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoxia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nitric Oxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03009643
org study id: STiNO
nct id: NCT03009643
lead sponsor: 
has dmc: No
Hypoxemia is a common complication after aortic surgery. As this complication has an adverse
      effect on the postoperative course of the patient, early treatment is important; however, the
      mechanism of hypoxemia after surgery for acute aortic dissection remains unclear. Recently,
      the investigators found that inhaled Nitric Oxide can improve the oxygenation in some of
      these patients. The investigators are trying to evaluate the effectiveness and safety of
      inhaled Nitric Oxide in patients with refractory hypoxemia after aortic surgery.
Several risk factors for severe hypoxemia after aortic surgery have been reported including
      advanced age, obesity, smoking history, previous heart surgery,emergency surgery,reduced
      cardiac function, advanced chronic obstructive pulmonary disease, excessive volume of blood
      transfusion,and prolonged CPB time. The routine treatment includes lung protective mechanical
      ventilation, recruitment maneuvers and glucocorticoids.

      No previous clinical studies have reported the effectiveness and safety of inhaled Nitric
      Oxide in patients with refractory hypoxemia after aortic surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Mechanical ventilation time (days)
time frame: During whole ICU stay. From date of randomization until the date of death or discharge from ICU, up to 6 months.
measure: ICU mortality
time frame: From date of randomization until the date of death or discharge from ICU, up to 6 months.
measure: length of hospital stay (days)
time frame: From date of randomization until the date of death or discharge from hospital, up to 6 months.
measure: length of ICU stay (days)
time frame: From date of randomization until the date of death or discharge from ICU, up to 6 months.
measure: hospital mortality
time frame: From date of randomization until the date of death or discharge from hospital, up to 6 months.
arm group label: iNO Group
arm group type: Experimental
description: Patients are treated with iNO at a concentration of 5-10 ppm for 3-5 days according to the clinical conditions
arm group label: Control
arm group type: Other
description: Patients are treated without iNO.
intervention type: Drug
intervention name: Inhaled Nitric Oxide
description: Patients are treated with iNO for 3-5 days.The concentration of inhaled Nitric Oxide is around 5-10ppm.
arm group label: iNO Group
intervention type: Device
intervention name: lung protective mechanical ventilation
description: Mechanical ventilation in the SIMV mode (ventilators Evita 2 or 4,Dräger, Lübeck, Germany) with VT 6-8ml/kg
arm group label: Control
arm group label: iNO Group
intervention type: Device
intervention name: Hemodynamic monitoring
description: Flotrac/Vigileo (Edwards Lifesciences) are used to guide the fluid management.
arm group label: Control
arm group label: iNO Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zhe Luo, PhD
role: Study Director
affiliation: Department of Critical Care Medicine
last name: Guo-wei Tu, MD
phone: +8613501996995
email: tu.guowei@zs-hospital.sh.cn
last name: Guo-guang Ma, MD
phone: +8615021519979
email: ma.guoguang@zs-hospital.sh.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: China
url: http://link.springer.com/article/10.1007%2Fs00595-006-3226-5
description: Springer
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649943/
description: biomed central
url: http://www.nature.com/nature/journal/v327/n6122/abs/327524a0.html
description: Nature Publishing Group
citation: Garcia-Delgado M, Navarrete-Sanchez I, Colmenero M. Preventing and managing perioperative pulmonary complications following cardiac surgery. Curr Opin Anaesthesiol. 2014 Apr;27(2):146-52. doi: 10.1097/ACO.0000000000000059.
PMID: 24514031
citation: Ball L, Battaglini D, Pelosi P. Postoperative respiratory disorders. Curr Opin Crit Care. 2016 Aug;22(4):379-85. doi: 10.1097/MCC.0000000000000312.
PMID: 27168252
citation: Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. 2005 Dec 22;353(25):2683-95. doi: 10.1056/NEJMra051884. No abstract available.
PMID: 16371634
citation: Nakajima T, Kawazoe K, Izumoto H, Kataoka T, Niinuma H, Shirahashi N. Risk factors for hypoxemia after surgery for acute type A aortic dissection. Surg Today. 2006;36(8):680-5. doi: 10.1007/s00595-006-3226-5.
PMID: 16865510
citation: Wang Y, Xue S, Zhu H. Risk factors for postoperative hypoxemia in patients undergoing Stanford A aortic dissection surgery. J Cardiothorac Surg. 2013 Apr 30;8:118. doi: 10.1186/1749-8090-8-118.
PMID: 23631417
citation: Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6. doi: 10.1038/327524a0.
PMID: 3495737
citation: Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation. 1991 Jun;83(6):2038-47. doi: 10.1161/01.cir.83.6.2038. Erratum In: Circulation 1991 Nov;84(5):2212.
PMID: 2040056
citation: Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology. 1993 Mar;78(3):427-35. doi: 10.1097/00000542-199303000-00005.
PMID: 8457043
citation: Benedetto M, Romano R, Baca G, Sarridou D, Fischer A, Simon A, Marczin N. Inhaled nitric oxide in cardiac surgery: Evidence or tradition? Nitric Oxide. 2015 Sep 15;49:67-79. doi: 10.1016/j.niox.2015.06.002. Epub 2015 Jul 14.
PMID: 26186889
citation: Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, Roy BJ, Keszler M, Kinsella JP. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med. 2000 Feb 17;342(7):469-74. doi: 10.1056/NEJM200002173420704.
PMID: 10675427
citation: Cornfield DN, Maynard RC, deRegnier RA, Guiang SF 3rd, Barbato JE, Milla CE. Randomized, controlled trial of low-dose inhaled nitric oxide in the treatment of term and near-term infants with respiratory failure and pulmonary hypertension. Pediatrics. 1999 Nov;104(5 Pt 1):1089-94. doi: 10.1542/peds.104.5.1089.
PMID: 10545552
responsible party type: Principal Investigator
investigator affiliation: Shanghai Zhongshan Hospital
investigator full name: Guowei Tu
investigator title: Attending doctor, Department of cardiac surgery intensive care unit, Principal Investigator
mesh term: Hypoxia
mesh term: Nitric Oxide
sharing ipd: No