<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/NCT02205242</url>
  </required_header>
  <id_info>
    <org_study_id>s55829 - PROactive Substudy</org_study_id>
    <nct_id>NCT02205242</nct_id>
  </id_info>
  <brief_title>BACE Trial Substudy 1 - PROactive Substudy</brief_title>
  <acronym>PROactive</acronym>
  <official_title>BACE Trial - Physical Activity as a Crucial Patient Reported Outcome in COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wim Janssens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pro-Active Medical Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>KU Leuven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A first sub-analysis of the BACE trial will address physical activity levels in a subgroup of&#xD;
      the intervention study with portable validated activity monitors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Physical activity is strongly reduced with exacerbations and failure to increase physical&#xD;
      activity is associated with relapse. In addition, physical inactivity is known to be&#xD;
      associated with cardiovascular and metabolic morbidity and is one of the strongest predictors&#xD;
      of mortality in COPD. Apart from potential direct effects of the intervention on treatment&#xD;
      failure and symptoms, positive effects on physical activity may offer considerable benefits&#xD;
      in the long run.&#xD;
&#xD;
      Randomized patients that are willing to participate in the sub-study will be monitored for&#xD;
      activity by validated and easy-to-wear portable devices (Dynaport®). This activity monitor&#xD;
      was recently thoroughly validated for use in COPD by the Pro-Active consortium and will be&#xD;
      used at the baseline, 3 months and 9 months visit. We hypothesize that with a positive&#xD;
      medical intervention, differences in recovery of physical activity will be appreciated.&#xD;
&#xD;
      Patients will follow the standard protocol but will also wear the activity monitor for 7 days&#xD;
      post discharge from hospital (at investigator discretion), at day 90 (end of treatment) and&#xD;
      at day 270 (end of follow-up). This device is not only registering physical activity for 7&#xD;
      days but is also coupled to a standardized and patient-validated questionnaire on physical&#xD;
      activities which needs to be filled out at day 8 to cover a recall period of 7 (monitored)&#xD;
      days.&#xD;
&#xD;
      Patient will have to give informed consent for the additional measures that are related to&#xD;
      the activity sub-study. However, individual patients can still opt out for these tests&#xD;
      (sub-study) and only participate in the medical intervention study (main study).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">April 2020</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <phase>Phase 3</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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in Physical Activity (total amount of steps) registered by the Dynaport® during 7 days between discharge from hospital (0 months) and 3 months after randomisation</measure>
    <time_frame>At discharge from hospital (0 months) and 3 months after start study drug intake</time_frame>
    <description>Physical activity will be quantified as Total amount of steps</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Key secondary endpoint: Different change in physical activity (total amount of steps) at 3 months between placebo and azithromycin arm</measure>
    <time_frame>0 and 3 months</time_frame>
    <description>Difference between placebo and azithromycin arm in physical activity changes registered by the Dynaport® during 7 days at discharge from hospital (0 months) and at 3 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Different change in physical activity (total amount of steps) at 9 months between placebo and azithromycin arm</measure>
    <time_frame>at baseline and 9 months</time_frame>
    <description>Difference between placebo and azithromycin arm in physical activity changes registered by the Dynaport® during 7 days at discharge from hospital (0 months) and at 9 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Physical Activity (TSMVA) registered by the Dynaport® during 7 days between discharge from hospital (0 months) and 9 months, or between 3 months and 9 months after randomisation</measure>
    <time_frame>baseline, 3 and 9 months</time_frame>
    <description>Physical activity will be specified for:&#xD;
Total amount of steps&#xD;
Total time spent in moderate to intense physical activity&#xD;
Sedentary Time (Lying-Sitting) and Time Active (Standing-Locomotion-Shuffeling)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Physical Activity (TSMVA) registered by the Dynaport® during 7 days between discharge from hospital (0 months) and 3 months after randomisation</measure>
    <time_frame>At discharge from hospital (0 months) and 3 months after start study drug intake</time_frame>
    <description>Physical activity will be specified for:&#xD;
Total time spent in moderate to intense physical activity&#xD;
Sedentary Time (Lying-Sitting) and Time Active (Standing-Locomotion-Shuffeling)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory endpoint: sensitivity analysis of primary and secondary endpoints in subgroups</measure>
    <time_frame>at 0, 3 and 9 months</time_frame>
    <description>Male vs female&#xD;
Smoker vs ex-smoker (stopped smoking &gt; 6 months)&#xD;
GOLD A, B vs GOLD C vs GOLD D&#xD;
Former GOLD I, II vs III vs IV&#xD;
High CRP (&gt; 50 mg/dL) vs low CRP (&lt; 50 mg/dL)&#xD;
Age &lt; 60 years vs age 60 - 70 years vs age &gt; 70 years&#xD;
Anthonissen I vs Anthonissen II vs Anthonissen III at admission&#xD;
ICS use vs no ICS use</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Azithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>N = 250 From day 1 up to and including day 3: 500 mg azithromycin PO once a day From day 4 up to and including day 90: 250 mg azithromycin PO once every 2 days&#xD;
N= 30 During 7 days post discharge from hospital (0 months), 3 months and 9 months, the patient will wear the Dynaport® which will register the patient's physical activity</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>N = 250 From day 1 up to and including day 3: 500 mg placebo PO once a day From day 4 up to and including day 90: 250 mg placebo PO once every 2 days&#xD;
N= 30 During 7 days post discharge from hospital (0 months), 3 months and 9 months, the patient will wear the Dynaport® which will register the patient's physical activity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azithromycin</intervention_name>
    <description>From day 1 up to and including day 3: 500 mg azithromycin or placebo PO once a day From day 4 up to and including day 90: 250 mg azithromycin or placebo PO once every 2 days</description>
    <arm_group_label>Azithromycin</arm_group_label>
    <other_name>Azitromcyine CF</other_name>
    <other_name>ATC code: J01FA10</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dynaport®</intervention_name>
    <description>Registering physical activity during 7 days post discharge from hospital (0 months), 3 months and 9 months</description>
    <arm_group_label>Azithromycin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Activity monitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Inactive substance</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Established diagnosis of COPD by medical doctor (based on clinical history OR&#xD;
             pulmonary function test)&#xD;
&#xD;
          -  Smoking history of at least 10 pack-years (10 pack-years are defined as 20 cigarettes&#xD;
             a day for 10 years, or 10 cigarettes a day for 20 years, etc.)&#xD;
&#xD;
          -  Current hospitalization for potential infectious AECOPD treated with standard therapy&#xD;
&#xD;
          -  History of at least one exacerbation during the last year (prior to the current&#xD;
             hospital admission) for which systemic steroids and/or antibiotics were taken&#xD;
&#xD;
          -  ECG at admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Mechanical or non-invasive ventilation at moment of randomization (D1)&#xD;
&#xD;
          -  Long QT interval on ECG (QTc &gt; 450msec for males or &gt; 470msec for females)&#xD;
&#xD;
          -  History of life-threatening arrhythmias&#xD;
&#xD;
          -  Myocardial infarction (NSTEMI or STEMI) less than 6 weeks before start of study drug&#xD;
&#xD;
          -  Unstable angina pectoris or acute myocardial infarction (NSTEMI or STEMI) at admission&#xD;
&#xD;
          -  Drugs with high risk for long QT interval and torsade de pointes (amiodarone,&#xD;
             flecainide, procainamide, sotalol, droperidol, haldol, citalopram, other macrolides)&#xD;
&#xD;
          -  Documented uncorrected severe hypokalemia (K+ &lt; 3.0 mmol/L) or hypomagnesemia (Mg2+ &lt;&#xD;
             0.5 mmol/L)&#xD;
&#xD;
          -  Chronic systemic steroids (&gt; 4 mg methylprednisolone /day for ≥ 2 months)&#xD;
&#xD;
          -  Actual use of macrolides for at least 2 weeks&#xD;
&#xD;
          -  Allergy to macrolides&#xD;
&#xD;
          -  Active cancer treatment&#xD;
&#xD;
          -  Life expectancy &lt; 3 months&#xD;
&#xD;
          -  Pregnant or breast-feeding subjects. Woman of childbearing potential must have a&#xD;
             pregnancy test performed and a negative result must be documented before start of&#xD;
             treatment&#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>Wim Janssens, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>KU Leuven</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Pieterziekenhuis</name>
      <address>
        <city>Brussel</city>
        <state>Brussels Hoofdstedelijk Gewest</state>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZNA Middelheim</name>
      <address>
        <city>Antwerpen</city>
        <state>Vlaanderen</state>
        <zip>2020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imelda Ziekenhuis</name>
      <address>
        <city>Bonheiden</city>
        <state>Vlaanderen</state>
        <zip>2820</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <state>Vlaanderen</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jessa Ziekenhuis</name>
      <address>
        <city>Hasselt</city>
        <state>Vlaanderen</state>
        <zip>3500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <state>Vlaanderen</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>April 7, 2020</last_update_submitted>
  <last_update_submitted_qc>April 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>KU Leuven</investigator_affiliation>
    <investigator_full_name>Wim Janssens</investigator_full_name>
    <investigator_title>MD. Phd.</investigator_title>
  </responsible_party>
  <keyword>AECOPD</keyword>
  <keyword>Chronic Obstructive Pulmonary Disease</keyword>
  <keyword>Acute exacerbation</keyword>
  <keyword>Hospitalization</keyword>
  <keyword>Azithromycin</keyword>
  <keyword>Macrolides</keyword>
  <keyword>Randomized Controlled Trial</keyword>
  <keyword>Placebo</keyword>
  <keyword>Physical Activity</keyword>
  <keyword>PRO-Active</keyword>
  <keyword>Activity Monitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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>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/NCT02205242
org study id: s55829 - PROactive Substudy
nct id: NCT02205242
lead sponsor: 
collaborator: 
has dmc: No
A first sub-analysis of the BACE trial will address physical activity levels in a subgroup of
      the intervention study with portable validated activity monitors.
Physical activity is strongly reduced with exacerbations and failure to increase physical
      activity is associated with relapse. In addition, physical inactivity is known to be
      associated with cardiovascular and metabolic morbidity and is one of the strongest predictors
      of mortality in COPD. Apart from potential direct effects of the intervention on treatment
      failure and symptoms, positive effects on physical activity may offer considerable benefits
      in the long run.

      Randomized patients that are willing to participate in the sub-study will be monitored for
      activity by validated and easy-to-wear portable devices (Dynaport®). This activity monitor
      was recently thoroughly validated for use in COPD by the Pro-Active consortium and will be
      used at the baseline, 3 months and 9 months visit. We hypothesize that with a positive
      medical intervention, differences in recovery of physical activity will be appreciated.

      Patients will follow the standard protocol but will also wear the activity monitor for 7 days
      post discharge from hospital (at investigator discretion), at day 90 (end of treatment) and
      at day 270 (end of follow-up). This device is not only registering physical activity for 7
      days but is also coupled to a standardized and patient-validated questionnaire on physical
      activities which needs to be filled out at day 8 to cover a recall period of 7 (monitored)
      days.

      Patient will have to give informed consent for the additional measures that are related to
      the activity sub-study. However, individual patients can still opt out for these tests
      (sub-study) and only participate in the medical intervention study (main study).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Difference in Physical Activity (total amount of steps) registered by the Dynaport® during 7 days between discharge from hospital (0 months) and 3 months after randomisation
time frame: At discharge from hospital (0 months) and 3 months after start study drug intake
description: Physical activity will be quantified as Total amount of steps
measure: Key secondary endpoint: Different change in physical activity (total amount of steps) at 3 months between placebo and azithromycin arm
time frame: 0 and 3 months
description: Difference between placebo and azithromycin arm in physical activity changes registered by the Dynaport® during 7 days at discharge from hospital (0 months) and at 3 months
measure: Different change in physical activity (total amount of steps) at 9 months between placebo and azithromycin arm
time frame: at baseline and 9 months
description: Difference between placebo and azithromycin arm in physical activity changes registered by the Dynaport® during 7 days at discharge from hospital (0 months) and at 9 months
measure: Difference in Physical Activity (TSMVA) registered by the Dynaport® during 7 days between discharge from hospital (0 months) and 9 months, or between 3 months and 9 months after randomisation
time frame: baseline, 3 and 9 months
description: Physical activity will be specified for:
Total amount of steps
Total time spent in moderate to intense physical activity
Sedentary Time (Lying-Sitting) and Time Active (Standing-Locomotion-Shuffeling)
measure: Difference in Physical Activity (TSMVA) registered by the Dynaport® during 7 days between discharge from hospital (0 months) and 3 months after randomisation
time frame: At discharge from hospital (0 months) and 3 months after start study drug intake
description: Physical activity will be specified for:
Total time spent in moderate to intense physical activity
Sedentary Time (Lying-Sitting) and Time Active (Standing-Locomotion-Shuffeling)
measure: Exploratory endpoint: sensitivity analysis of primary and secondary endpoints in subgroups
time frame: at 0, 3 and 9 months
description: Male vs female
Smoker vs ex-smoker (stopped smoking > 6 months)
GOLD A, B vs GOLD C vs GOLD D
Former GOLD I, II vs III vs IV
High CRP (> 50 mg/dL) vs low CRP (< 50 mg/dL)
Age < 60 years vs age 60 - 70 years vs age > 70 years
Anthonissen I vs Anthonissen II vs Anthonissen III at admission
ICS use vs no ICS use
arm group label: Azithromycin
arm group type: Experimental
description: N = 250 From day 1 up to and including day 3: 500 mg azithromycin PO once a day From day 4 up to and including day 90: 250 mg azithromycin PO once every 2 days
N= 30 During 7 days post discharge from hospital (0 months), 3 months and 9 months, the patient will wear the Dynaport® which will register the patient's physical activity
arm group label: Placebo
arm group type: Placebo Comparator
description: N = 250 From day 1 up to and including day 3: 500 mg placebo PO once a day From day 4 up to and including day 90: 250 mg placebo PO once every 2 days
N= 30 During 7 days post discharge from hospital (0 months), 3 months and 9 months, the patient will wear the Dynaport® which will register the patient's physical activity
intervention type: Drug
intervention name: Azithromycin
description: From day 1 up to and including day 3: 500 mg azithromycin or placebo PO once a day From day 4 up to and including day 90: 250 mg azithromycin or placebo PO once every 2 days
arm group label: Azithromycin
other name: Azitromcyine CF
other name: ATC code: J01FA10
intervention type: Device
intervention name: Dynaport®
description: Registering physical activity during 7 days post discharge from hospital (0 months), 3 months and 9 months
arm group label: Azithromycin
arm group label: Placebo
other name: Activity monitor
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
other name: Inactive substance
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wim Janssens, MD PhD
role: Principal Investigator
affiliation: KU Leuven
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
responsible party type: Sponsor-Investigator
investigator affiliation: KU Leuven
investigator full name: Wim Janssens
investigator title: MD. Phd.
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Azithromycin
sharing ipd: No