<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/NCT03282019</url>
  </required_header>
  <id_info>
    <org_study_id>TRIRES1668</org_study_id>
    <secondary_id>UMIN000028581</secondary_id>
    <nct_id>NCT03282019</nct_id>
  </id_info>
  <brief_title>Study of Long-term HFNC for COPD Patients With HOT</brief_title>
  <acronym>FLOCOP</acronym>
  <official_title>Efficacy and Safety of Long-term High-flow Nasal Cannula Oxygen Therapy in Stable COPD Patients With Home Oxygen Therapy (HOT): a Multicenter, Prospective, Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kobe City Medical Center General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, randomized parallel study for evaluation of the efficacy and safety of&#xD;
      long-term nocturnal high-flow nasal cannula therapy (HFNC: with the myAIRVO2 as HFNC in this&#xD;
      study) in stable COPD patients with the global initiative for chronic obstructive lung&#xD;
      disease (GOLD) stage 2-4, PaCO2 &gt;= 45 Torr and hypercapnia who require home oxygen therapy&#xD;
      (HOT) using COPD exacerbation (Moderate or Severe).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An abroad study of the stable COPD patients was reported that HFNC usage decreased the&#xD;
      frequency of COPD exacerbation.&#xD;
&#xD;
      In addition, the result of the pilot study (NCT02545855) of the stable COPD patient in Japan&#xD;
      is indicated that HOT with HFNC improved their QOL and PaCO2 by comparing to HOT only.&#xD;
&#xD;
      Therefore, this study is planned to indicate the efficacy of HFNC which can increase the&#xD;
      ventilation efficiency and have the function of heated humidification, by comparing HOT with&#xD;
      HFNC to HOT only.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 6, 2017</start_date>
  <completion_date type="Actual">October 28, 2020</completion_date>
  <primary_completion_date type="Actual">October 28, 2020</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 (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency (the number of occurrences per year) of COPD exacerbation (Moderate or Severe)</measure>
    <time_frame>52weeks</time_frame>
    <description>COPD exacerbation will be assessed by the disease diary which is kept by each patient within the term of intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Term from enrollment to the date of first COPD exacerbation (Moderate or Severe)</measure>
    <time_frame>up to 52 weeks</time_frame>
    <description>The term from enrollment to the date of first COPD exacerbation is a duration from the start of intervention (Week0) to the date of first COPD exacerbation or death from any cause which ever comes first.&#xD;
The date of first COPD exacerbation will be assessed by the disease diary which is kept by each patient within the term of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Term from enrollment to death from any cause</measure>
    <time_frame>up to 52 weeks</time_frame>
    <description>Term from enrollment to death from any cause is a duration from the start of intervention (Week0) to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency (the number of occurrences per year) of COPD exacerbation (All Severity and Severe only)</measure>
    <time_frame>52weeks</time_frame>
    <description>COPD exacerbation will be assessed by the disease diary which is kept by each patient within the term of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total St. George's respiratory questionnaire (SGRQ-C) score, and each components score (symptom score, activity score, and impact score)</measure>
    <time_frame>at 0, 12, 24 and 52 weeks</time_frame>
    <description>SGRQ-C score will be assessed by Japanese version of the SGRQ-C value sets including each components score (symptom score, activity score, and impact score).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality-adjusted life year (QALY) by mapping the EQ-5D-5L utility scores</measure>
    <time_frame>at 0, 12, 24 and 52 weeks</time_frame>
    <description>Quality-adjusted life year (QALY) of the subjects will be assessed by Japanese version of the EQ-5D-5L value sets including assessment of changes from baseline in the EQ-5D-5L utility index scores and visual analogue scale scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total SRI (Severe Respiratory Insufficiency Questionnaire) score</measure>
    <time_frame>at 0, 12, 24 and 52 weeks</time_frame>
    <description>Total SRI score will be assessed by Japanese version of the SRI value sets.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total PSQI-J(Japanese version of the Pittsburgh Sleep Quality Index) score</measure>
    <time_frame>at 0, 12, 24 and 52 weeks</time_frame>
    <description>Total PSQI-J score will be assessed by Japanese version of the PSQI value sets.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspnea intensity: the modified medical research council (mMRC) score</measure>
    <time_frame>52weeks</time_frame>
    <description>Dyspnea intensity will be evaluated by the modified medical research council (mMRC) score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial blood gas analysis (ABG): pH, PaO2, PaCO2, HCO3-, BE</measure>
    <time_frame>52weeks</time_frame>
    <description>ABG will be evaluated by the blood gas analysis equipment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen Saturation (SpO2)</measure>
    <time_frame>52weeks</time_frame>
    <description>SpO2 will be evaluated by Pulse Oximeter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary functions: FVC, FEV1, FEV1%</measure>
    <time_frame>52weeks</time_frame>
    <description>Lung function of the subjects will be assessed by the pulmonary function tests in the following indicators: vital capacity (VC, %VC), forced vital capacity (FVC, %FVC), forced expiratory volume in 1 second (FEV1, ％FEV1), FEV1/FVC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-minute walk test (6MWT)</measure>
    <time_frame>at 0, 12, 24 and 52 weeks</time_frame>
    <description>6MWT for the respiration rehabilitation is defined as the functional exercise capacity which is assessed by the following indicators: the distance (m), changes in pre- and post-6MWT pulse oximeter (SpO2), and post-6MWT modified borg scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Term from enrollment to the date of long-term (more than 1month) NPPV(Noninvasive Positive Pressure Ventilation) usage</measure>
    <time_frame>52weeks</time_frame>
    <description>The term from the start of intervention (Week0) to the date of Long-term NPPV usage.&#xD;
Long-term NPPV usage is defined as more than 1month NPPV usage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flow rate(Oxygen / Total) (Arm A only)</measure>
    <time_frame>52weeks</time_frame>
    <description>Oxygen flow rate / Total flow rate will be confirmed by the record of numerical value displayed on the device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total hours of myAIRVO2-use (Arm A only)</measure>
    <time_frame>52weeks</time_frame>
    <description>Total hours of myAIRVO2-use will be confirmed by the record of numerical value displayed on the device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>52weeks</time_frame>
    <description>Adverse events will be determined by the latest version of MedDRA/J （Medical Dictionary for Regulatory Activities/J）at the time of Database lock.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Correlation between frequency of COPD exacerbation (All Severity and Severe only) and amount of ABG change</measure>
    <time_frame>52weeks</time_frame>
    <description>Amount of ABG change will be calculated by the ABG value at before and after the intervention.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation between frequency of COPD exacerbation (All Severity and Severe only) and amount of SpO2 change</measure>
    <time_frame>52weeks</time_frame>
    <description>Amount of SpO2 change will be calculated by the ABG value of before and after the intervention.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>Arm A(myAIRVO2® + HOT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive following protocol treatment; Home oxygen therapy (HOT) plus nocturnal high-flow nasal cannula therapy with the myAIRVO2 within 52weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B(HOT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects receive following protocol treatment; Home oxygen therapy (HOT) only within 52weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High-flow nasal cannula therapy</intervention_name>
    <description>Subjects will receive nocturnal high-flow nasal cannula therapy with the myAIRVO2®, in addition to their current Home oxygen therapy (HOT). The myAIRVO2® is used for at least 4 hours per day with flow rates in the range 30-40 L/min. The investigator can adjust the nocturnal oxygen flow rates to keep SpO2 88-92% stably. If the subjects report discomfort, the investigator can adjust the flow rates in the range at least 20 L/min.</description>
    <arm_group_label>Arm A(myAIRVO2® + HOT)</arm_group_label>
    <other_name>myAIRVO2®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Home oxygen therapy (HOT)</intervention_name>
    <description>All subjects will continue their current Home oxygen therapy (HOT) which kept original usage conditions at the time of enrollment throughout the entire duration of the study regardless of treatment arm assignment.</description>
    <arm_group_label>Arm A(myAIRVO2® + HOT)</arm_group_label>
    <arm_group_label>Arm B(HOT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients who are diagnosed with the global initiative on obstructive lung disease&#xD;
             (GOLD) stage 2-4 COPD.&#xD;
&#xD;
          2. Patients who have received nocturnal HOT 16 hours or more per day for 1 month or more&#xD;
             at the time of the informed consent.&#xD;
&#xD;
          3. Patients with PaCO2 &gt;= 45 Torr and pH &gt;= 7.35 at screening.&#xD;
&#xD;
          4. Patients with COPD exacerbation (Moderate or Severe; judged by the investigators)&#xD;
             within the past 1 year prior to the informed consent.&#xD;
&#xD;
          5. Patients who are more than 40 years old at the time of the informed consent.&#xD;
&#xD;
          6. Patients who agree to participate in the study with the written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with severe kidney, liver or cardiovascular disease.&#xD;
&#xD;
          2. Patients with active malignant tumor.&#xD;
&#xD;
          3. Patients with acute disease.&#xD;
&#xD;
          4. Patients who are diagnosed with asthma. (Excluding COPD patients with history of&#xD;
             asthma).&#xD;
&#xD;
          5. Patients who have any history of obstructive sleep apnea syndrome (OSAS) or are&#xD;
             highly-suspected cases in the clinical. (Excluding patients who are denied the&#xD;
             diagnosis of OSAS by the result of overnight polysomnography.)&#xD;
&#xD;
          6. Patients with diseases that affecting the efficacy endpoints (for example: active&#xD;
             pulmonary infection, clinically significant pulmonary fibrosis and bronchiectasis,&#xD;
             α-1-antitrypsin deficiency etc.,) and are regarded as inadequate for the study by the&#xD;
             investigators.&#xD;
&#xD;
          7. Patients who have experienced a COPD exacerbation (any Severity: judged by the&#xD;
             investigators) within the past 4 weeks prior to the informed consent.&#xD;
&#xD;
          8. Patients who are receiving nocturnal noninvasive positive pressure ventilation (NPPV),&#xD;
             or who had been received it within 4 weeks prior to the informed consent.&#xD;
&#xD;
          9. Patients who have used HFNC at home within the past 1 year prior to the informed&#xD;
             consent, or are using any HFNC. (Excluding patients who used HFNC during&#xD;
             hospitalization due to acute respiratory failure within 1 year prior to the informed&#xD;
             consent.)&#xD;
&#xD;
         10. Patients with history of tracheotomy, severe pharyngeal surgery or severe nasal cavity&#xD;
             surgery within the past 6 months prior to the informed consent.&#xD;
&#xD;
         11. Patients who are pregnant.&#xD;
&#xD;
         12. Patients with cognitive impairment or mental disorder who are regarded as inadequate&#xD;
             to evaluate for the study by the investigators.&#xD;
&#xD;
         13. Patients who are regarded as being unable to operate the myAIRVO2 adequately at home&#xD;
             by the investigators.&#xD;
&#xD;
         14. Patients who have participated in the other study at the time of the informed consent,&#xD;
             or will participate in the other study.&#xD;
&#xD;
         15. Any other cases who are regarded as inadequate for the study enrollment by the&#xD;
             investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Keisuke Tomii, MD, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kobe City Medical Center General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kobe City Medical Center General Hospital</name>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <zip>6500047</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>January 5, 2021</last_update_submitted>
  <last_update_submitted_qc>January 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>myAIRVO2</keyword>
  <keyword>high-flow nasal cannula therapy</keyword>
  <keyword>home oxygen therapy</keyword>
  <keyword>HOT</keyword>
  <keyword>COPD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03282019
org study id: TRIRES1668
secondary id: UMIN000028581
nct id: NCT03282019
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a prospective, randomized parallel study for evaluation of the efficacy and safety of
      long-term nocturnal high-flow nasal cannula therapy (HFNC: with the myAIRVO2 as HFNC in this
      study) in stable COPD patients with the global initiative for chronic obstructive lung
      disease (GOLD) stage 2-4, PaCO2 >= 45 Torr and hypercapnia who require home oxygen therapy
      (HOT) using COPD exacerbation (Moderate or Severe).
An abroad study of the stable COPD patients was reported that HFNC usage decreased the
      frequency of COPD exacerbation.

      In addition, the result of the pilot study (NCT02545855) of the stable COPD patient in Japan
      is indicated that HOT with HFNC improved their QOL and PaCO2 by comparing to HOT only.

      Therefore, this study is planned to indicate the efficacy of HFNC which can increase the
      ventilation efficiency and have the function of heated humidification, by comparing HOT with
      HFNC to HOT only.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Frequency (the number of occurrences per year) of COPD exacerbation (Moderate or Severe)
time frame: 52weeks
description: COPD exacerbation will be assessed by the disease diary which is kept by each patient within the term of intervention.
measure: Term from enrollment to the date of first COPD exacerbation (Moderate or Severe)
time frame: up to 52 weeks
description: The term from enrollment to the date of first COPD exacerbation is a duration from the start of intervention (Week0) to the date of first COPD exacerbation or death from any cause which ever comes first.
The date of first COPD exacerbation will be assessed by the disease diary which is kept by each patient within the term of intervention.
measure: Term from enrollment to death from any cause
time frame: up to 52 weeks
description: Term from enrollment to death from any cause is a duration from the start of intervention (Week0) to death from any cause.
measure: Frequency (the number of occurrences per year) of COPD exacerbation (All Severity and Severe only)
time frame: 52weeks
description: COPD exacerbation will be assessed by the disease diary which is kept by each patient within the term of intervention.
measure: Total St. George's respiratory questionnaire (SGRQ-C) score, and each components score (symptom score, activity score, and impact score)
time frame: at 0, 12, 24 and 52 weeks
description: SGRQ-C score will be assessed by Japanese version of the SGRQ-C value sets including each components score (symptom score, activity score, and impact score).
measure: Quality-adjusted life year (QALY) by mapping the EQ-5D-5L utility scores
time frame: at 0, 12, 24 and 52 weeks
description: Quality-adjusted life year (QALY) of the subjects will be assessed by Japanese version of the EQ-5D-5L value sets including assessment of changes from baseline in the EQ-5D-5L utility index scores and visual analogue scale scores.
measure: Total SRI (Severe Respiratory Insufficiency Questionnaire) score
time frame: at 0, 12, 24 and 52 weeks
description: Total SRI score will be assessed by Japanese version of the SRI value sets.
measure: Total PSQI-J(Japanese version of the Pittsburgh Sleep Quality Index) score
time frame: at 0, 12, 24 and 52 weeks
description: Total PSQI-J score will be assessed by Japanese version of the PSQI value sets.
measure: Dyspnea intensity: the modified medical research council (mMRC) score
time frame: 52weeks
description: Dyspnea intensity will be evaluated by the modified medical research council (mMRC) score.
measure: Arterial blood gas analysis (ABG): pH, PaO2, PaCO2, HCO3-, BE
time frame: 52weeks
description: ABG will be evaluated by the blood gas analysis equipment.
measure: Oxygen Saturation (SpO2)
time frame: 52weeks
description: SpO2 will be evaluated by Pulse Oximeter.
measure: Pulmonary functions: FVC, FEV1, FEV1%
time frame: 52weeks
description: Lung function of the subjects will be assessed by the pulmonary function tests in the following indicators: vital capacity (VC, %VC), forced vital capacity (FVC, %FVC), forced expiratory volume in 1 second (FEV1, ％FEV1), FEV1/FVC.
measure: 6-minute walk test (6MWT)
time frame: at 0, 12, 24 and 52 weeks
description: 6MWT for the respiration rehabilitation is defined as the functional exercise capacity which is assessed by the following indicators: the distance (m), changes in pre- and post-6MWT pulse oximeter (SpO2), and post-6MWT modified borg scale.
measure: Term from enrollment to the date of long-term (more than 1month) NPPV(Noninvasive Positive Pressure Ventilation) usage
time frame: 52weeks
description: The term from the start of intervention (Week0) to the date of Long-term NPPV usage.
Long-term NPPV usage is defined as more than 1month NPPV usage.
measure: Flow rate(Oxygen / Total) (Arm A only)
time frame: 52weeks
description: Oxygen flow rate / Total flow rate will be confirmed by the record of numerical value displayed on the device.
measure: Total hours of myAIRVO2-use (Arm A only)
time frame: 52weeks
description: Total hours of myAIRVO2-use will be confirmed by the record of numerical value displayed on the device.
measure: Adverse events
time frame: 52weeks
description: Adverse events will be determined by the latest version of MedDRA/J （Medical Dictionary for Regulatory Activities/J）at the time of Database lock.
measure: Correlation between frequency of COPD exacerbation (All Severity and Severe only) and amount of ABG change
time frame: 52weeks
description: Amount of ABG change will be calculated by the ABG value at before and after the intervention.
measure: Correlation between frequency of COPD exacerbation (All Severity and Severe only) and amount of SpO2 change
time frame: 52weeks
description: Amount of SpO2 change will be calculated by the ABG value of before and after the intervention.
arm group label: Arm A(myAIRVO2® + HOT)
arm group type: Experimental
description: Subjects receive following protocol treatment; Home oxygen therapy (HOT) plus nocturnal high-flow nasal cannula therapy with the myAIRVO2 within 52weeks.
arm group label: Arm B(HOT)
arm group type: Active Comparator
description: Subjects receive following protocol treatment; Home oxygen therapy (HOT) only within 52weeks.
intervention type: Device
intervention name: High-flow nasal cannula therapy
description: Subjects will receive nocturnal high-flow nasal cannula therapy with the myAIRVO2®, in addition to their current Home oxygen therapy (HOT). The myAIRVO2® is used for at least 4 hours per day with flow rates in the range 30-40 L/min. The investigator can adjust the nocturnal oxygen flow rates to keep SpO2 88-92% stably. If the subjects report discomfort, the investigator can adjust the flow rates in the range at least 20 L/min.
arm group label: Arm A(myAIRVO2® + HOT)
other name: myAIRVO2®
intervention type: Device
intervention name: Home oxygen therapy (HOT)
description: All subjects will continue their current Home oxygen therapy (HOT) which kept original usage conditions at the time of enrollment throughout the entire duration of the study regardless of treatment arm assignment.
arm group label: Arm A(myAIRVO2® + HOT)
arm group label: Arm B(HOT)
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Keisuke Tomii, MD, Ph.D.
role: Principal Investigator
affiliation: Kobe City Medical Center General Hospital
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: Undecided