<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/NCT02217683</url>
  </required_header>
  <id_info>
    <org_study_id>BloodiNO</org_study_id>
    <nct_id>NCT02217683</nct_id>
  </id_info>
  <brief_title>Use of Inhaled Nitric Oxide to Prevent Pulmonary Hypertension Associated to Stored Blood Transfusion</brief_title>
  <official_title>Pulmonary Hemodynamic Effects of Stored Red Blood Cell Transfusion in Post-Operative Cardiac Surgical Patients: Influence of Breathing Nitric Oxide. A Randomized Controlled Trial in the Cardiac-Intensive Care Unit.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to assess if prolonged storage time of a packed red blood cell&#xD;
      unit may cause pulmonary vasoconstriction after transfusion, in a susceptible population such&#xD;
      as cardiac surgery patients. The investigators will also evaluate the potential reversal&#xD;
      effect of Inhaled Nitric Oxide on pulmonary vasoconstriction induced by stored blood&#xD;
      transfusions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be randomized into one of the three groups:&#xD;
&#xD;
      I. Blood transfusion stored for less than 10 days II. Blood transfusion stored for more than&#xD;
      30 days III. Blood transfusion stored for more than 30 days days plus inhalation of Nitric&#xD;
      Oxide at 80 part per million for an hour during blood transfusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    This trial never started due to lack of funding.&#xD;
  </why_stopped>
  <start_date>March 2016</start_date>
  <completion_date type="Anticipated">April 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary vascular resistance index</measure>
    <time_frame>During and after blood transfusion- average time of observation 6 hours</time_frame>
    <description>Parameters to calculate pulmonary vascular resistance index will be measured during and after blood transfusion for about 6 hours. The following parameters will be recorded: height, weight, systemic pressure, pulmonary pressure, wedge pressure, central venous pressure, cardiac output) of each subjects will be recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemolysis</measure>
    <time_frame>During and after blood transfusion- average time of observation 6 hours</time_frame>
    <description>Hemolytic markers will be measured such as: haptoglobin, plasma free hemoglobin, hemopexin, and iron metabolites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nitric oxide metabolites</measure>
    <time_frame>During and after blood transfusion- average time of observation 6 hours</time_frame>
    <description>Plasma nitric oxide consumption, plasma and red blood cell levels of circulating nitrate, nitrite, nitric will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation</measure>
    <time_frame>During and after blood transfusion- average time of observation 6 hours</time_frame>
    <description>Inflammation will be assessed by changes of the plasma concentration of cytokines, such as IL-6, IL-8, IL-10, IL-12, TNF, IFN-γ</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hypertension, Pulmonary</condition>
  <condition>Hemolysis</condition>
  <arm_group>
    <arm_group_label>Young blood transfusion</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The first group of patients (n=30) will be randomized to receive leukoreduced blood transfusion stored for less than 10 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Old blood transfusion</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Old blood transfusion and Nitric Oxide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days while breathing nitric oxide (80 part per million) and oxygen</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitric Oxide</intervention_name>
    <description>Nitric oxide at 80 part per million will be administrated by inhalation for approximately 1 hour during the blood transfusion</description>
    <arm_group_label>Old blood transfusion and Nitric Oxide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide written informed consent&#xD;
&#xD;
          2. Elective cardiac or aortic surgery&#xD;
&#xD;
          3. One or more blood transfusions scheduled for clinical reasons&#xD;
&#xD;
          4. Presence of an arterial catheter and pulmonary arterial catheter&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Emergent cardiac surgery.&#xD;
&#xD;
          2. Patients requiring irradiated or washed blood transfusions.&#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>Lorenzo Berra, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Berra L, Pinciroli R, Stowell CP, Wang L, Yu B, Fernandez BO, Feelisch M, Mietto C, Hod EA, Chipman D, Scherrer-Crosbie M, Bloch KD, Zapol WM. Autologous transfusion of stored red blood cells increases pulmonary artery pressure. Am J Respir Crit Care Med. 2014 Oct 1;190(7):800-7. doi: 10.1164/rccm.201405-0850OC.</citation>
    <PMID>25162920</PMID>
  </reference>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>March 16, 2016</last_update_submitted>
  <last_update_submitted_qc>March 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 18, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Lorenzo Berra, MD</investigator_full_name>
    <investigator_title>Staff anesthesiologist</investigator_title>
  </responsible_party>
  <keyword>Catheterization, Swan-Ganz</keyword>
  <keyword>Cardiac Surgical Procedures</keyword>
  <keyword>Blood Transfusion</keyword>
  <keyword>Nitric Oxide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Hemolysis</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>
  <!-- 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/NCT02217683
org study id: BloodiNO
nct id: NCT02217683
lead sponsor: 
has dmc: Yes
The objective of this study is to assess if prolonged storage time of a packed red blood cell
      unit may cause pulmonary vasoconstriction after transfusion, in a susceptible population such
      as cardiac surgery patients. The investigators will also evaluate the potential reversal
      effect of Inhaled Nitric Oxide on pulmonary vasoconstriction induced by stored blood
      transfusions.
Patients will be randomized into one of the three groups:

      I. Blood transfusion stored for less than 10 days II. Blood transfusion stored for more than
      30 days III. Blood transfusion stored for more than 30 days days plus inhalation of Nitric
      Oxide at 80 part per million for an hour during blood transfusion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Pulmonary vascular resistance index
time frame: During and after blood transfusion- average time of observation 6 hours
description: Parameters to calculate pulmonary vascular resistance index will be measured during and after blood transfusion for about 6 hours. The following parameters will be recorded: height, weight, systemic pressure, pulmonary pressure, wedge pressure, central venous pressure, cardiac output) of each subjects will be recorded.
measure: Hemolysis
time frame: During and after blood transfusion- average time of observation 6 hours
description: Hemolytic markers will be measured such as: haptoglobin, plasma free hemoglobin, hemopexin, and iron metabolites.
measure: Nitric oxide metabolites
time frame: During and after blood transfusion- average time of observation 6 hours
description: Plasma nitric oxide consumption, plasma and red blood cell levels of circulating nitrate, nitrite, nitric will be measured
measure: Inflammation
time frame: During and after blood transfusion- average time of observation 6 hours
description: Inflammation will be assessed by changes of the plasma concentration of cytokines, such as IL-6, IL-8, IL-10, IL-12, TNF, IFN-γ
arm group label: Young blood transfusion
arm group type: No Intervention
description: The first group of patients (n=30) will be randomized to receive leukoreduced blood transfusion stored for less than 10 days
arm group label: Old blood transfusion
arm group type: No Intervention
description: This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days
arm group label: Old blood transfusion and Nitric Oxide
arm group type: Active Comparator
description: This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days while breathing nitric oxide (80 part per million) and oxygen
intervention type: Drug
intervention name: Nitric Oxide
description: Nitric oxide at 80 part per million will be administrated by inhalation for approximately 1 hour during the blood transfusion
arm group label: Old blood transfusion and Nitric Oxide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lorenzo Berra, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
citation: Berra L, Pinciroli R, Stowell CP, Wang L, Yu B, Fernandez BO, Feelisch M, Mietto C, Hod EA, Chipman D, Scherrer-Crosbie M, Bloch KD, Zapol WM. Autologous transfusion of stored red blood cells increases pulmonary artery pressure. Am J Respir Crit Care Med. 2014 Oct 1;190(7):800-7. doi: 10.1164/rccm.201405-0850OC.
PMID: 25162920
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Lorenzo Berra, MD
investigator title: Staff anesthesiologist
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Hemolysis
mesh term: Nitric Oxide