<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/NCT04481555</url>
  </required_header>
  <id_info>
    <org_study_id>COPERNICOS_JUJCPR</org_study_id>
    <secondary_id>2020-003014-12</secondary_id>
    <nct_id>NCT04481555</nct_id>
  </id_info>
  <brief_title>Eosinophil-guided Reduction of Inhaled Corticosteroids</brief_title>
  <acronym>COPERNICOS</acronym>
  <official_title>Eosinophil-guided Reduction of Inhaled Corticosteroids</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chronic Obstructive Pulmonary Disease Trial Network, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chronic Obstructive Pulmonary Disease Trial Network, Denmark</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>
      Clinical trial on eosinophil-guided time-updated person-specific reduction of inhaled&#xD;
      corticosteroid (ICS) therapy and prophylactic azithromycin therapy in patients with severe or&#xD;
      very severe chronic obstructive pulmonary disease (COPD) receiving long-acting b-agonist&#xD;
      (LABA) / long-acting muscarinic receptor antagonists (LAMA) / ICS treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 28, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>4-arm facultative designed, randomized controlled, multicenter, parallel group, double-blinded (azithromycin), non-inferiority intervention study in patients with severe and very severe COPD study.&#xD;
Participants will be randomly allocated to one of four treatment groups.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Days alive</measure>
    <time_frame>365 days</time_frame>
    <description>Days alive and out of hospital within 365 days after recruitment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exacerbations, hospital</measure>
    <time_frame>365 days</time_frame>
    <description>Number of hospitalization-requiring exacerbations within 12 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AECOPD tendency</measure>
    <time_frame>365 dyas</time_frame>
    <description>Death or &quot;uncontrolled AECOPD tendency&quot; within 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of exacerbations</measure>
    <time_frame>365 days</time_frame>
    <description>Number of moderate/severe exacerbation within 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative ICS dose</measure>
    <time_frame>365 days</time_frame>
    <description>Cumulative dose of ICS within 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative OCS dose</measure>
    <time_frame>365 days</time_frame>
    <description>Cumulative dose of systemic corticosteroids within 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in FEV1</measure>
    <time_frame>365 days</time_frame>
    <description>Change in lung function (ΔFEV1) from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood eosinophils</measure>
    <time_frame>365 days</time_frame>
    <description>Change in blood eosinophils (eosinophilic trajectories)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetes mellitus</measure>
    <time_frame>365 days</time_frame>
    <description>New diagnosis of diabetes mellitus within 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>365 days</time_frame>
    <description>Change in HbA1c from baseline to 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of antibiotic requiring infections</measure>
    <time_frame>365 days</time_frame>
    <description>Antibiotic-requiring infections within 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiota</measure>
    <time_frame>180 days</time_frame>
    <description>Change in lunge microbiota abundance and diversity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CAT score</measure>
    <time_frame>365 days</time_frame>
    <description>Change in COPD Assessment Test from baseline to final visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in MRC dyspnoea score</measure>
    <time_frame>365 days</time_frame>
    <description>MRC-dyspnea score from &lt; 3 to 3 ≥, fron baseline, 3 ,6 ,9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of non-invasive ventilation (NIV) or intensive care admissions or death</measure>
    <time_frame>365 days</time_frame>
    <description>Number of admission-requiring NIV treatment or admissions to intensive care or death within 365 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>365 days</time_frame>
    <description>Death within 365 days</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">444</enrollment>
  <condition>COPD</condition>
  <condition>Inhaled Corticosteroid</condition>
  <condition>Azithromycin</condition>
  <condition>COPD Exacerbation</condition>
  <condition>Pneumonia</condition>
  <arm_group>
    <arm_group_label>Eosinophil_&quot;Control&quot;/Azithro_&quot;Control&quot;</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Azithromycin: patients are given placebo&#xD;
ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Eosinophil_&quot;Active&quot;/Azithro_&quot;Control&quot;:</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>a. Azithromycin: placebo b. ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months): i. If blood eosinophil ≥ 300 cells/μL, ICS in usual dose next 3 months. Blood eosinophils are measured every 3 months.&#xD;
ii. If blood eosinophil &lt;300 cells/μL, ICS is discontinued.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Eosinophil_&quot;Control&quot;/Azithro_&quot;Active&quot; group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azithromycin: 250 mg azithromycin three times weekly. b. ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose, where the medical treatment for severe COPD is unchanged throughout the entire project period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Eosinophil_&quot;Active&quot;/Azithro_&quot;Active&quot;:</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azithromycin: 250 mg azithromycin three times weekly.&#xD;
ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months):</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azithromycin</intervention_name>
    <description>Prophylactic azithromycin treatment 250 mg three times weekly vs placebo</description>
    <arm_group_label>Eosinophil_&quot;Active&quot;/Azithro_&quot;Active&quot;:</arm_group_label>
    <arm_group_label>Eosinophil_&quot;Control&quot;/Azithro_&quot;Active&quot; group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ICS</intervention_name>
    <description>All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months) vs continued LABA/LAMA/ICS treatment</description>
    <arm_group_label>Eosinophil_&quot;Active&quot;/Azithro_&quot;Active&quot;:</arm_group_label>
    <arm_group_label>Eosinophil_&quot;Active&quot;/Azithro_&quot;Control&quot;:</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD (verified by a specialist in respiratory medicine + spirometry)&#xD;
&#xD;
          -  GOLD risk class C/D anytime within the last 2 years (corresponding to 2 ≥ AECOPD&#xD;
             and/or ≥1 AECOPD leading to hospitalization during a 12 months period within the last&#xD;
             2 years) and/or FEV1&lt;30%.&#xD;
&#xD;
          -  Must receive at least during last 4 weeks: LAMA, LABA and ICS&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known asthma.&#xD;
&#xD;
          -  Male &lt; 40 years.&#xD;
&#xD;
          -  Female &lt;40 years, if non-menopausal (had menstruation within the last 12 months)&#xD;
             conditioned by a negative urine HCG test&#xD;
&#xD;
          -  Severe mental illness which considerably complicates co-operation.&#xD;
&#xD;
          -  Language problems that considerably complicate co-operation.&#xD;
&#xD;
          -  Current treatment with systemic corticosteroids corresponding to &gt; 5 mg prednisolone&#xD;
             per day.&#xD;
&#xD;
          -  Systemic antibiotic treatment or systemic corticosteroid treatment within 14 days&#xD;
             (also prophylactic Azithromycin).&#xD;
&#xD;
          -  Contra-indication to treat with Azithromycin (as listed by the producer).&#xD;
&#xD;
          -  Non-bacterial exacerbation per investigator judgement in the last 3 months.&#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_contact>
    <last_name>Jens-Ulrik Jensen</last_name>
    <phone>38673057</phone>
    <phone_ext>45</phone_ext>
    <email>jens.ulrik.jensen@regionh.dk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Elisabeth Bendstrup, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hvidovre Hospital</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Charlotte Ulrik</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sydvestjysk Sygehus Esbjerg</name>
      <address>
        <city>Esbjerg</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Torben Jensen</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gentofte Hospital</name>
      <address>
        <city>Hellerup</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Rønn</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nordsjællands Hospital</name>
      <address>
        <city>Hillerød</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Browatzki</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Næstved-Slagelse-Ringsted Sygehus</name>
      <address>
        <city>Næstved</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Uffe Bødtger</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Odense University Hospital</name>
      <address>
        <city>Odense</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Sofie L Johansson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Roskilde Sygehus</name>
      <address>
        <city>Roskilde</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Meyer</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>August 28, 2023</last_update_submitted>
  <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azithromycin</mesh_term>
  </intervention_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/NCT04481555
org study id: COPERNICOS_JUJCPR
secondary id: 2020-003014-12
nct id: NCT04481555
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Clinical trial on eosinophil-guided time-updated person-specific reduction of inhaled
      corticosteroid (ICS) therapy and prophylactic azithromycin therapy in patients with severe or
      very severe chronic obstructive pulmonary disease (COPD) receiving long-acting b-agonist
      (LABA) / long-acting muscarinic receptor antagonists (LAMA) / ICS treatment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 4-arm facultative designed, randomized controlled, multicenter, parallel group, double-blinded (azithromycin), non-inferiority intervention study in patients with severe and very severe COPD study.
Participants will be randomly allocated to one of four treatment groups.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Days alive
time frame: 365 days
description: Days alive and out of hospital within 365 days after recruitment
measure: Exacerbations, hospital
time frame: 365 days
description: Number of hospitalization-requiring exacerbations within 12 months
measure: AECOPD tendency
time frame: 365 dyas
description: Death or "uncontrolled AECOPD tendency" within 365 days
measure: Number of exacerbations
time frame: 365 days
description: Number of moderate/severe exacerbation within 12 months
measure: Cumulative ICS dose
time frame: 365 days
description: Cumulative dose of ICS within 365 days
measure: Cumulative OCS dose
time frame: 365 days
description: Cumulative dose of systemic corticosteroids within 365 days
measure: Change in FEV1
time frame: 365 days
description: Change in lung function (ΔFEV1) from baseline
measure: Change in blood eosinophils
time frame: 365 days
description: Change in blood eosinophils (eosinophilic trajectories)
measure: Diabetes mellitus
time frame: 365 days
description: New diagnosis of diabetes mellitus within 365 days
measure: Change in HbA1c
time frame: 365 days
description: Change in HbA1c from baseline to 365 days
measure: Number of antibiotic requiring infections
time frame: 365 days
description: Antibiotic-requiring infections within 365 days
measure: Microbiota
time frame: 180 days
description: Change in lunge microbiota abundance and diversity
measure: Change in CAT score
time frame: 365 days
description: Change in COPD Assessment Test from baseline to final visit
measure: Change in MRC dyspnoea score
time frame: 365 days
description: MRC-dyspnea score from < 3 to 3 ≥, fron baseline, 3 ,6 ,9 and 12 months
measure: Number of non-invasive ventilation (NIV) or intensive care admissions or death
time frame: 365 days
description: Number of admission-requiring NIV treatment or admissions to intensive care or death within 365 days
measure: Mortality
time frame: 365 days
description: Death within 365 days
arm group label: Eosinophil_"Control"/Azithro_"Control"
arm group type: No Intervention
description: Azithromycin: patients are given placebo
ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose.
arm group label: Eosinophil_"Active"/Azithro_"Control":
arm group type: Experimental
description: a. Azithromycin: placebo b. ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months): i. If blood eosinophil ≥ 300 cells/μL, ICS in usual dose next 3 months. Blood eosinophils are measured every 3 months.
ii. If blood eosinophil <300 cells/μL, ICS is discontinued.
arm group label: Eosinophil_"Control"/Azithro_"Active" group
arm group type: Experimental
description: Azithromycin: 250 mg azithromycin three times weekly. b. ICS: The patients are given the usual LAMA/LABA/ICS product in the usual dose, where the medical treatment for severe COPD is unchanged throughout the entire project period
arm group label: Eosinophil_"Active"/Azithro_"Active":
arm group type: Experimental
description: Azithromycin: 250 mg azithromycin three times weekly.
ICS: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months):
intervention type: Drug
intervention name: Azithromycin
description: Prophylactic azithromycin treatment 250 mg three times weekly vs placebo
arm group label: Eosinophil_"Active"/Azithro_"Active":
arm group label: Eosinophil_"Control"/Azithro_"Active" group
intervention type: Drug
intervention name: ICS
description: All patients will receive LABA/LAMA medication. The ICS medication will be switched on/off according to the most recent blood eosinophil count (at inclusion + every 3 months) vs continued LABA/LAMA/ICS treatment
arm group label: Eosinophil_"Active"/Azithro_"Active":
arm group label: Eosinophil_"Active"/Azithro_"Control":
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Jens-Ulrik Jensen
phone: 38673057
phone ext: 45
email: jens.ulrik.jensen@regionh.dk
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
contact: 
country: Denmark
responsible party type: Sponsor
mesh term: Respiratory Aspiration
mesh term: Azithromycin
sharing ipd: Undecided