<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/NCT03262142</url>
  </required_header>
  <id_info>
    <org_study_id>coptrin2</org_study_id>
    <nct_id>NCT03262142</nct_id>
  </id_info>
  <brief_title>Targeted AntiBiotics for Chronic Pulmonary Diseases</brief_title>
  <acronym>Target-ABC</acronym>
  <official_title>Targeted AntiBiotics for Chronic Pulmonary Disease: Can Targeted Antibiotic Therapy Improve the Prognosis of Pseudomonas Aeruginosa Infected Patients With Chronic Pulmonary Obstructive Disease, Non-cystic Fibrosis Bronchiectasis and Asthma? A Multicenter, Randomized, Controlled, Open-label Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chronic Obstructive Pulmonary Disease Trial Network, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Center for Genomic Medicine, Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, randomized multi-center trial investigating the impact of lower airway&#xD;
      infection with P. aeruginosa in COPD patients. The aim of the study is to evaluate if&#xD;
      targeted antibiotic therapy against P. aeruginosa can improve the prognosis in patients with&#xD;
      COPD. non-CF bronchiectasis (BE) and asthma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      P. aeruginosa represents a potentially significant cause of acute exacerbation of chronic&#xD;
      pulmonary diseases and is possibly associated with significant morbidity and mortality.&#xD;
      Despite this, the role of P. aeruginosa in the course of COPD, non-CF BE and asthma is less&#xD;
      well characterized, and evidence based guidelines for management and treatment of the&#xD;
      bacteria are lacking.&#xD;
&#xD;
      P. aeruginosa is more likely to be isolated from patients with more advanced disease and&#xD;
      severely impaired lung function. It is, however, difficult to draw definitive conclusions&#xD;
      regarding the extent to which the bacteria contributes to adverse clinical outcomes since&#xD;
      severely reduced lung function by itself is a strong predictor of mortality in patients with&#xD;
      chronic pulmonary disease. Infection with P. aeruginosa might therefore be secondary to&#xD;
      damaged lung tissue and decreased lung function, and thereby have no independent impact on&#xD;
      the prognosis&#xD;
&#xD;
      So far, and to the investigators best knowledge, no randomized controlled trial has been&#xD;
      conducted to investigate whether specific antibiotic treatment of P. aeruginosa can reduce&#xD;
      the risk of new exacerbations and improve the long-term prognosis in patients with COPD,&#xD;
      non-CF BE and asthma.&#xD;
&#xD;
      In Denmark, the first choice of treatment for P. aeruginosa is usually a 10-14 day therapy of&#xD;
      intravenous combination treatment of P. aeruginosa active antibiotics&#xD;
      (piperacillin/tazobactam and ciprofloxacin).&#xD;
&#xD;
      The aim of the study is to investigate whether the intervention with targeted pseudomonas&#xD;
      active antibiotics can reduce the loss of lung function, reduce the frequency of&#xD;
      exacerbations and mortality.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">January 10, 2018</start_date>
  <completion_date type="Actual">March 1, 2023</completion_date>
  <primary_completion_date type="Actual">March 1, 2023</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>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to prednisolone and/or antibiotic requiring exacerbation or death, in primary or secondary health care sectors from day 20 to day 365 from randomization.</measure>
    <time_frame>day 20-365</time_frame>
    <description>Time alive and without exacerbation between day 20-365 from the date of recruitment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Days alive and without hospitalisation from day 20 to day 365 from randomization.</measure>
    <time_frame>day 20-365</time_frame>
    <description>Days alive and out of hospital between day 20-365 from the date of recruitment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of re-admissions with pulmonary exacerbation within 365 days from randomization.</measure>
    <time_frame>365 days</time_frame>
    <description>Number of re-admissions with pulmonary exacerbation within 365 days from randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death within 365 days from randomization.</measure>
    <time_frame>365 days</time_frame>
    <description>Death within 365 days from randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiological cure</measure>
    <time_frame>90 days</time_frame>
    <description>Microbiological cure = P. aeruginosa-negative sputum culture until day 90.&#xD;
Non-microbiological cure = positive sputum culture with same P.aeruginosa clone as baseline clone ≤ day 90.&#xD;
Re-infection = positive sputum culture with different P. aeruginosa clone compare to baseline clone ≤ day 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical cure</measure>
    <time_frame>14 days</time_frame>
    <description>Resolution or improvement of clinical symptoms related to P. aeruginosa within day 14.&#xD;
Clinical failure = persistent of worsened clinical symptoms related to P. aeruginosa within day 14.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.</measure>
    <time_frame>90 days</time_frame>
    <description>Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.</measure>
    <time_frame>90 days</time_frame>
    <description>Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decrease of ≥ 200 ml in FEV1 from randomization to day 365.</measure>
    <time_frame>365 days</time_frame>
    <description>Decrease of ≥ 200 ml in FEV1 from randomization to day 365.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in COPD Assessment Test (CAT) from randomization to day 90.</measure>
    <time_frame>90 days</time_frame>
    <description>Change in COPD Assessment Test (CAT) from randomization to day 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body mass index (BMI) from randomization to day 90.</measure>
    <time_frame>90 days</time_frame>
    <description>Change in body mass index (BMI) from randomization to day 90.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>COPD</condition>
  <condition>Respiratory Tract Infections</condition>
  <condition>Pseudomonas Aeruginosa</condition>
  <condition>Bronchiectasis</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Standard antibiotic treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous Piperacillin/tazobactam + oral Ciprofloxacin for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antibiotic-free treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No antibiotic treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Piperacillin/tazobactam</intervention_name>
    <description>Intravenous Piperacillin/tazobactam four times daily</description>
    <arm_group_label>Standard antibiotic treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ciprofloxacin</intervention_name>
    <description>Oral Ciprofloxacin twice daily</description>
    <arm_group_label>Standard antibiotic treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  P. aeruginosa-positive lower respiratory tract sample.&#xD;
&#xD;
          -  COPD, non-CF bronchiectasis, or asthma verified by a respiratory specialist based on&#xD;
             clinical assessment and additional tests: COPD: spirometry; Asthma: reversibility;&#xD;
             Non-CF bronchiectasis: high-resolution computed tomography scan.&#xD;
&#xD;
          -  Minimum of two previous exacerbations, or one previous hospitalization-requiring or&#xD;
             emergency room-demanding exacerbation, with the treatment of systemic prednisolone&#xD;
             and/or antibiotics within the last 12 months.&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Immune-modulating therapy (except ≤ 10 mg prednisolone/day)&#xD;
&#xD;
          -  Men &lt; 40 years&#xD;
&#xD;
          -  Women &lt;= 55 years&#xD;
&#xD;
          -  Non- menopausal women &gt; 55 years&#xD;
&#xD;
          -  Life expectancy &lt; 90 days&#xD;
&#xD;
          -  Severe mental illness&#xD;
&#xD;
          -  Severe language difficulties or inability to provide informed consent&#xD;
&#xD;
          -  Known drug allergy to 1) Fluoroquinolones and 2) both Piperacillin/tazobactam,&#xD;
             Cephalosporins and Carbapenems&#xD;
&#xD;
          -  Attempted eradication of P. aeruginosa x 2 within the last 12months, or completed&#xD;
             eradication therapy within the last 14 days&#xD;
&#xD;
          -  The investigator 's opinion is that the participant requires antibiotic treatment.&#xD;
             This exclusion criterion must be discussed with the coordinating investigator before&#xD;
             the final decision on exclusion is taken.&#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>Jens-Ulrik Jensen, MD, Consultant, Phd</last_name>
    <role>Study Director</role>
    <affiliation>Chronic Obstructive Pulmonary Disease Trial Network, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Herlev and Gentofte Hospital</name>
      <address>
        <city>Hellerup</city>
        <state>Copenhagen</state>
        <zip>2900</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>http://coptrin.dk/</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Eklof J, Alispahic IA, Sivapalan P, Wilcke T, Seersholm N, Armbruster K, Kjaergaard JL, Saeed MI, Nielsen TL, Browatzki A, Overgaard RH, Fenlev CS, Harboe ZB, Andreassen HF, Lapperre TS, Pedersen L, Johnsen S, Ulrik CS, Janner J, Moberg M, Heidemann M, Weinreich UM, Vijdea R, Linde H, Titlestad I, Johansson SL, Rosenvinge FS, Ostergaard C, Ghathian KSA, Gundersen L, Christensen CW, Bangsborg J, Jensen TT, Sorensen VM, Ellingsgaard T, Datcu R, Coia JE, Bodtger U, Jensen JUS. Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial. Trials. 2022 Sep 27;23(1):817. doi: 10.1186/s13063-022-06720-z.</citation>
    <PMID>36167555</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>May 24, 2023</last_update_submitted>
  <last_update_submitted_qc>May 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chronic Obstructive Pulmonary Disease Trial Network, Denmark</investigator_affiliation>
    <investigator_full_name>Josefin Eklöf</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>chronic pulmonary disease</keyword>
  <keyword>Pseudomonas Aeruginosa</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>Pseudomonas Infections</mesh_term>
    <mesh_term>Asthma</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Bronchiectasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciprofloxacin</mesh_term>
    <mesh_term>Tazobactam</mesh_term>
    <mesh_term>Piperacillin</mesh_term>
    <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT03262142
org study id: coptrin2
nct id: NCT03262142
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, randomized multi-center trial investigating the impact of lower airway
      infection with P. aeruginosa in COPD patients. The aim of the study is to evaluate if
      targeted antibiotic therapy against P. aeruginosa can improve the prognosis in patients with
      COPD. non-CF bronchiectasis (BE) and asthma.
P. aeruginosa represents a potentially significant cause of acute exacerbation of chronic
      pulmonary diseases and is possibly associated with significant morbidity and mortality.
      Despite this, the role of P. aeruginosa in the course of COPD, non-CF BE and asthma is less
      well characterized, and evidence based guidelines for management and treatment of the
      bacteria are lacking.

      P. aeruginosa is more likely to be isolated from patients with more advanced disease and
      severely impaired lung function. It is, however, difficult to draw definitive conclusions
      regarding the extent to which the bacteria contributes to adverse clinical outcomes since
      severely reduced lung function by itself is a strong predictor of mortality in patients with
      chronic pulmonary disease. Infection with P. aeruginosa might therefore be secondary to
      damaged lung tissue and decreased lung function, and thereby have no independent impact on
      the prognosis

      So far, and to the investigators best knowledge, no randomized controlled trial has been
      conducted to investigate whether specific antibiotic treatment of P. aeruginosa can reduce
      the risk of new exacerbations and improve the long-term prognosis in patients with COPD,
      non-CF BE and asthma.

      In Denmark, the first choice of treatment for P. aeruginosa is usually a 10-14 day therapy of
      intravenous combination treatment of P. aeruginosa active antibiotics
      (piperacillin/tazobactam and ciprofloxacin).

      The aim of the study is to investigate whether the intervention with targeted pseudomonas
      active antibiotics can reduce the loss of lung function, reduce the frequency of
      exacerbations and mortality.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Time to prednisolone and/or antibiotic requiring exacerbation or death, in primary or secondary health care sectors from day 20 to day 365 from randomization.
time frame: day 20-365
description: Time alive and without exacerbation between day 20-365 from the date of recruitment.
measure: Days alive and without hospitalisation from day 20 to day 365 from randomization.
time frame: day 20-365
description: Days alive and out of hospital between day 20-365 from the date of recruitment.
measure: Number of re-admissions with pulmonary exacerbation within 365 days from randomization.
time frame: 365 days
description: Number of re-admissions with pulmonary exacerbation within 365 days from randomization.
measure: Death within 365 days from randomization.
time frame: 365 days
description: Death within 365 days from randomization.
measure: Microbiological cure
time frame: 90 days
description: Microbiological cure = P. aeruginosa-negative sputum culture until day 90.
Non-microbiological cure = positive sputum culture with same P.aeruginosa clone as baseline clone ≤ day 90.
Re-infection = positive sputum culture with different P. aeruginosa clone compare to baseline clone ≤ day 90.
measure: Clinical cure
time frame: 14 days
description: Resolution or improvement of clinical symptoms related to P. aeruginosa within day 14.
Clinical failure = persistent of worsened clinical symptoms related to P. aeruginosa within day 14.
measure: Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.
time frame: 90 days
description: Number of days with non-invasive ventilation or invasive ventilation within 90 days from randomization.
measure: Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.
time frame: 90 days
description: Change in forced expiratory volume in the first second (FEV1) from randomization to day 90.
measure: Decrease of ≥ 200 ml in FEV1 from randomization to day 365.
time frame: 365 days
description: Decrease of ≥ 200 ml in FEV1 from randomization to day 365.
measure: Change in COPD Assessment Test (CAT) from randomization to day 90.
time frame: 90 days
description: Change in COPD Assessment Test (CAT) from randomization to day 90.
measure: Change in body mass index (BMI) from randomization to day 90.
time frame: 90 days
description: Change in body mass index (BMI) from randomization to day 90.
arm group label: Standard antibiotic treatment
arm group type: Active Comparator
description: Intravenous Piperacillin/tazobactam + oral Ciprofloxacin for 14 days
arm group label: Antibiotic-free treatment
arm group type: No Intervention
description: No antibiotic treatment
intervention type: Drug
intervention name: Piperacillin/tazobactam
description: Intravenous Piperacillin/tazobactam four times daily
arm group label: Standard antibiotic treatment
intervention type: Drug
intervention name: Ciprofloxacin
description: Oral Ciprofloxacin twice daily
arm group label: Standard antibiotic treatment
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Jens-Ulrik Jensen, MD, Consultant, Phd
role: Study Director
affiliation: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
facility: 
country: Denmark
url: http://coptrin.dk/
description: Related Info
citation: Eklof J, Alispahic IA, Sivapalan P, Wilcke T, Seersholm N, Armbruster K, Kjaergaard JL, Saeed MI, Nielsen TL, Browatzki A, Overgaard RH, Fenlev CS, Harboe ZB, Andreassen HF, Lapperre TS, Pedersen L, Johnsen S, Ulrik CS, Janner J, Moberg M, Heidemann M, Weinreich UM, Vijdea R, Linde H, Titlestad I, Johansson SL, Rosenvinge FS, Ostergaard C, Ghathian KSA, Gundersen L, Christensen CW, Bangsborg J, Jensen TT, Sorensen VM, Ellingsgaard T, Datcu R, Coia JE, Bodtger U, Jensen JUS. Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial. Trials. 2022 Sep 27;23(1):817. doi: 10.1186/s13063-022-06720-z.
PMID: 36167555
responsible party type: Principal Investigator
investigator affiliation: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
investigator full name: Josefin Eklöf
investigator title: Principal Investigator
mesh term: Respiratory Tract Infections
mesh term: Pseudomonas Infections
mesh term: Asthma
mesh term: Lung Diseases
mesh term: Bronchiectasis
mesh term: Ciprofloxacin
mesh term: Tazobactam
mesh term: Piperacillin
mesh term: Piperacillin, Tazobactam Drug Combination
sharing ipd: Yes