<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/NCT03008642</url>
  </required_header>
  <id_info>
    <org_study_id>PI2016_843_0032</org_study_id>
    <nct_id>NCT03008642</nct_id>
  </id_info>
  <brief_title>CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia</brief_title>
  <acronym>Poly-CO</acronym>
  <official_title>CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia: a Multicentric Study. Co-Rebreathing for the Measurement of Total Red Cell Mass in Polycythemia.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire, Amiens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire, Amiens</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The optimized CO-Rebreathing is an efficient method to evaluate the red cell mass and has&#xD;
      been used in the vast majority of studies in sport medicine. However, this method has never&#xD;
      been evaluated on a large scale in the diagnosis of primitive or secondary polycythemia. The&#xD;
      standard procedure to evaluate the red cell mass is based on isotopic measurement using&#xD;
      Cr51-labelled red cells, but its lack of availability in many centers highlights the need for&#xD;
      a non-invasive and rapid alternative method. The purpose of this study is to evaluate and&#xD;
      validate the CO-Rebreathing method in this set of indications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The definition of a true polycythemia is stricto sensu an increased red cell mass (RCM) above&#xD;
      125% of the expected value depending on the size and the weight of the patient. However, this&#xD;
      measurement requires an isotopic labeling of red cells and is not available in most of the&#xD;
      hospitals. Therefore, the diagnosis of polycythemia, and particularly Polycythemia Vera (PV)&#xD;
      is based on routine red blood cells parameters, i.e. hemoglobin level and hematocrit. If&#xD;
      these parameters are efficient in marked polycythemia, discrepancies have been observed in&#xD;
      milder cases. Two situations where a RCM evaluation is particularly required can be&#xD;
      described:&#xD;
&#xD;
        -  In patients with a hematocrit level between 52 and 60% (men) or between 48 and 56%&#xD;
           (women) in order to limit invasive investigations to patients with a confirmed&#xD;
           polycythemia diagnosis&#xD;
&#xD;
        -  In JAK2V617F positive myeloproliferative neoplasms (MPN) with hematocrit and hemoglobin&#xD;
           levels under the PV cut-off in order to discriminate between masked PV and essential&#xD;
           thrombocythemia CO-Rebreathing is a fast, non invasive alternative method for RCM&#xD;
           evaluation. It is based on the high affinity of carbon monoxide (CO) for hemoglobin. The&#xD;
           decrease in the HbCO percentage after CO inhalation is dependent on the total hemoglobin&#xD;
           mass from which RCM can be obtained. The investigators propose a tri-centric study&#xD;
           evaluating CO-Rebreathing as an alternative tool to measure RCM in the diagnosis of&#xD;
           polycythemia in the two categories of patients described above.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Actual">May 1, 2020</completion_date>
  <primary_completion_date type="Actual">May 1, 2020</primary_completion_date>
  <phase>N/A</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>equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia</measure>
    <time_frame>1 month</time_frame>
    <description>The primary outcome is to prove the equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AE / SAE / EI</measure>
    <time_frame>1 month</time_frame>
    <description>Incidence, grade type according to NCI-CTCAE v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of thrombotic and hemorrhagic complications</measure>
    <time_frame>1 month</time_frame>
    <description>Cumulative incidence of thrombotic and hemorrhagic complications List according to PT1 protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Deaths and causes</measure>
    <time_frame>1 month</time_frame>
    <description>Deaths and causes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of the results of VGTCO and VGTi</measure>
    <time_frame>1 month</time_frame>
    <description>Analysis of the results of VGTCO and VGTi as a function of hemoglobin and hematocrit</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Polycythemia</condition>
  <arm_group>
    <arm_group_label>CO-Rebreathing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CO-Rebreathing technique at diagnosis of polycythemia</intervention_name>
    <description>The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.</description>
    <arm_group_label>CO-Rebreathing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patient&#xD;
&#xD;
          2. Informed consent obtained&#xD;
&#xD;
          3. Requirement of an isotopic red cell mass determination:&#xD;
&#xD;
             a - Hematocrit between 52 and 60% (men) or 48 and 56% (women) with no argument for a&#xD;
             PV (JAK2V617F negative, EPO level normal/high).&#xD;
&#xD;
             b - Patients with a JAK2V617F positive MPN and a hematocrit level between 46 and 50%&#xD;
             (women) or 48 and 52% for men.&#xD;
&#xD;
          4. No recent vascular event (&lt;6 mois)&#xD;
&#xD;
          5. No unstable coronaropathy&#xD;
&#xD;
          6. Non smoking since 24 hours.&#xD;
&#xD;
          7. ECOG &lt;2&#xD;
&#xD;
          8. Negativity of pregnancy test/effective contraception for childbearing age women,&#xD;
&#xD;
          9. Health insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Recent venous event &lt;1 months, cerebral stroke &lt; 6 mois)&#xD;
&#xD;
          2. Evolutive cardiopathy (&lt; 6 months)&#xD;
&#xD;
          3. Chronic Respiratory failure&#xD;
&#xD;
          4. Smokers with no withdrawal in the last 24 hours before CO-Rebreathing&#xD;
&#xD;
          5. Basal HbCO&gt;7% the day of CO-Rebreathing&#xD;
&#xD;
          6. Pregnant or breast feeding women&#xD;
&#xD;
          7. Patient enable to give an informed consent&#xD;
&#xD;
          8. Inclusion in an interventional clinical trial in the last three months.&#xD;
&#xD;
          9. Any contraindication to lung function testing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Loïc GARCON, professor</last_name>
    <role>Study Director</role>
    <affiliation>CHU Amiens-Picardie</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lydia ROY, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Henri Mondor, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marjolaine GEORGES, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Universitaire Dijon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Amiens Picardie</name>
      <address>
        <city>Amiens</city>
        <state>Picardie</state>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Polycythemia</keyword>
  <keyword>CO-Rebreathing</keyword>
  <keyword>red cell mass determination</keyword>
  <keyword>myeloproliferative neoplasms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycythemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03008642
org study id: PI2016_843_0032
nct id: NCT03008642
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The optimized CO-Rebreathing is an efficient method to evaluate the red cell mass and has
      been used in the vast majority of studies in sport medicine. However, this method has never
      been evaluated on a large scale in the diagnosis of primitive or secondary polycythemia. The
      standard procedure to evaluate the red cell mass is based on isotopic measurement using
      Cr51-labelled red cells, but its lack of availability in many centers highlights the need for
      a non-invasive and rapid alternative method. The purpose of this study is to evaluate and
      validate the CO-Rebreathing method in this set of indications.
The definition of a true polycythemia is stricto sensu an increased red cell mass (RCM) above
      125% of the expected value depending on the size and the weight of the patient. However, this
      measurement requires an isotopic labeling of red cells and is not available in most of the
      hospitals. Therefore, the diagnosis of polycythemia, and particularly Polycythemia Vera (PV)
      is based on routine red blood cells parameters, i.e. hemoglobin level and hematocrit. If
      these parameters are efficient in marked polycythemia, discrepancies have been observed in
      milder cases. Two situations where a RCM evaluation is particularly required can be
      described:

        -  In patients with a hematocrit level between 52 and 60% (men) or between 48 and 56%
           (women) in order to limit invasive investigations to patients with a confirmed
           polycythemia diagnosis

        -  In JAK2V617F positive myeloproliferative neoplasms (MPN) with hematocrit and hemoglobin
           levels under the PV cut-off in order to discriminate between masked PV and essential
           thrombocythemia CO-Rebreathing is a fast, non invasive alternative method for RCM
           evaluation. It is based on the high affinity of carbon monoxide (CO) for hemoglobin. The
           decrease in the HbCO percentage after CO inhalation is dependent on the total hemoglobin
           mass from which RCM can be obtained. The investigators propose a tri-centric study
           evaluating CO-Rebreathing as an alternative tool to measure RCM in the diagnosis of
           polycythemia in the two categories of patients described above.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia
time frame: 1 month
description: The primary outcome is to prove the equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia.
measure: AE / SAE / EI
time frame: 1 month
description: Incidence, grade type according to NCI-CTCAE v4.0
measure: Cumulative incidence of thrombotic and hemorrhagic complications
time frame: 1 month
description: Cumulative incidence of thrombotic and hemorrhagic complications List according to PT1 protocol.
measure: Deaths and causes
time frame: 1 month
description: Deaths and causes
measure: Analysis of the results of VGTCO and VGTi
time frame: 1 month
description: Analysis of the results of VGTCO and VGTi as a function of hemoglobin and hematocrit
arm group label: CO-Rebreathing
arm group type: Experimental
description: The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.
intervention type: Other
intervention name: CO-Rebreathing technique at diagnosis of polycythemia
description: The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.
arm group label: CO-Rebreathing
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Loïc GARCON, professor
role: Study Director
affiliation: CHU Amiens-Picardie
last name: Lydia ROY, Doctor
role: Principal Investigator
affiliation: CHU Henri Mondor, France
last name: Marjolaine GEORGES, Doctor
role: Principal Investigator
affiliation: Centre Hospitalier Universitaire Dijon
facility: 
country: France
responsible party type: Sponsor
mesh term: Polycythemia