<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/NCT02196493</url>
  </required_header>
  <id_info>
    <org_study_id>13031</org_study_id>
    <secondary_id>2013-002938-20</secondary_id>
    <nct_id>NCT02196493</nct_id>
  </id_info>
  <brief_title>An Open Label Trial of Azithromycin in Chronic Productive Cough</brief_title>
  <acronym>AZCC</acronym>
  <official_title>An Open Label Trial of Azithromycin in Chronic Productive Cough</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We have noticed a group of patients presenting with a longstanding wet cough which has often&#xD;
      been treated as asthma. The cough is productive of sputum which frequently contains bacteria,&#xD;
      but does not resolve with standard antibiotic treatment.&#xD;
&#xD;
      A very similar cough is seen in subjects who smoke, have exposure to airbourne dusts or&#xD;
      chemicals or have a condition known as bronchiectasis, but these problems have already been&#xD;
      excluded.&#xD;
&#xD;
      We have found that prolonged treatment with an antibiotic called azithromycin is very&#xD;
      effective but using azithromycin in this way is not licensed and there is currently no trial&#xD;
      evidence to support its use.&#xD;
&#xD;
      This research will evaluate the clinical benefit of low dose azithromycin to determine if&#xD;
      this is an effective and safe treatment for these patients. It will also involve a detailed&#xD;
      investigation of these patients to determine whether they have enough in common to believe we&#xD;
      are describing a new condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We and others have observed a cohort of patients, mainly referred with either poorly&#xD;
      controlled asthma despite high dose treatment or suspected bronchiectasis, who give a history&#xD;
      of chronic (often 3 months or more) productive cough which improves with antibiotic treatment&#xD;
      but quickly relapses. Most deny wheeze and on examination there are often transmitted sounds&#xD;
      from mucus in the large airways but no expiratory wheeze typical of asthma. Investigations&#xD;
      including spirometry, bronchial challenges, chest X-ray, screen for immunodeficiency and high&#xD;
      resolution CT (HRCT) scan exclude recognised causes of productive cough but sputum culture is&#xD;
      often positive for Haemophilus influenzae although sometimes demonstrates normal respiratory&#xD;
      flora despite being markedly purulent.&#xD;
&#xD;
      Due to their efficacy in cystic fibrosis and bronchiectasis we have empirically tried&#xD;
      treatment with low dose macrolide antibiotics over 3-6 months often with dramatic benefit.&#xD;
      This is however an unproven and unlicensed indication which needs to be more thoroughly&#xD;
      evaluated.&#xD;
&#xD;
      The key objective of the study is to determine if 12 weeks treatment of patients with chronic&#xD;
      productive cough with low dose azithromycin is both effective and safe.&#xD;
&#xD;
      The secondary objectives of the study are to describe the clinical and pathological features&#xD;
      of a cohort of patients who present with chronic productive cough (with no evidence of&#xD;
      bronchiectasis, smoking-related chronic bronchitis or immunodeficiency) to determine if these&#xD;
      are sufficiently similar to justify a new diagnostic label.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2013</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in cough on the Leicester Cough Questionnaire (LCQ) score at week 12</measure>
    <time_frame>12 weeks after treatment started</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in sputum colour (as per previously validated commercially available graded sputum colour chart) at week 12</measure>
    <time_frame>12 weeks after treatment started</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in exhaled nitric oxide level (ppm) at week 24</measure>
    <time_frame>12 weeks after treatment started</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in FEV1 (ml) at week 24</measure>
    <time_frame>12 weeks after treatment started</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in sputum volume (ml) at week 12</measure>
    <time_frame>12 weeks after treatment started</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Chronic Cough</condition>
  <arm_group>
    <arm_group_label>Azithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>250mg azithromycin three times weekly for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azithromycin</intervention_name>
    <description>250mg azithromycin three times per week for 12 weeks</description>
    <arm_group_label>Azithromycin</arm_group_label>
    <other_name>Zithromax</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 and over&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  Non-smokers for 10 years and &lt;20 pack year equivalents in total&#xD;
&#xD;
          -  Persistent productive cough for &gt; 3 months in duration&#xD;
&#xD;
          -  Use of effective contraception Acceptable contraceptive methods include: established&#xD;
             use of oral, injected or implanted hormonal methods; placement of an intrauterine&#xD;
             device (IUD) or intrauterine system (IUS); condom or occlusive cap (diaphragm or&#xD;
             cervical/vault caps) with spermicide; true abstinence (when this is in line with the&#xD;
             preferred and usual lifestyle of the participant); or vasectomised partner.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of obvious inhaled irritant exposure&#xD;
&#xD;
          -  Evidence of primary or secondary immunodeficiency.&#xD;
&#xD;
          -  Clinically important bronchiectasis on HRCT scan&#xD;
&#xD;
          -  Prolonged QT interval on ECG or significant cardiac pathology prior to commencing&#xD;
             azithromycin&#xD;
&#xD;
          -  Abnormal LFT's (greater than 2x upper limit of normal)&#xD;
&#xD;
          -  Hypersensitivity to azithromycin or any macrolide/ketolide antibiotic&#xD;
&#xD;
          -  Pregnancy or intent to become pregnant during course of study&#xD;
&#xD;
          -  Contra-indication to bronchoscopy (as per British Thoracic Society Guidelines)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim Harrison, MD, FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Matthew Martin, MBChB</last_name>
    <phone>01158231935</phone>
    <email>matthew.martin@nottingham.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Respiratory Research Unit</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthew Martin, MBChB</last_name>
      <phone>01158231935</phone>
    </contact>
    <investigator>
      <last_name>Tim Harrison, MD, FRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Matthew Martin, MBChB MRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>February 17, 2016</last_update_submitted>
  <last_update_submitted_qc>February 17, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 18, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Productive</keyword>
  <keyword>Cough</keyword>
  <keyword>Bronchitis</keyword>
  <keyword>Azithromycin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cough</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/NCT02196493
org study id: 13031
secondary id: 2013-002938-20
nct id: NCT02196493
lead sponsor: 
has dmc: No
We have noticed a group of patients presenting with a longstanding wet cough which has often
      been treated as asthma. The cough is productive of sputum which frequently contains bacteria,
      but does not resolve with standard antibiotic treatment.

      A very similar cough is seen in subjects who smoke, have exposure to airbourne dusts or
      chemicals or have a condition known as bronchiectasis, but these problems have already been
      excluded.

      We have found that prolonged treatment with an antibiotic called azithromycin is very
      effective but using azithromycin in this way is not licensed and there is currently no trial
      evidence to support its use.

      This research will evaluate the clinical benefit of low dose azithromycin to determine if
      this is an effective and safe treatment for these patients. It will also involve a detailed
      investigation of these patients to determine whether they have enough in common to believe we
      are describing a new condition.
We and others have observed a cohort of patients, mainly referred with either poorly
      controlled asthma despite high dose treatment or suspected bronchiectasis, who give a history
      of chronic (often 3 months or more) productive cough which improves with antibiotic treatment
      but quickly relapses. Most deny wheeze and on examination there are often transmitted sounds
      from mucus in the large airways but no expiratory wheeze typical of asthma. Investigations
      including spirometry, bronchial challenges, chest X-ray, screen for immunodeficiency and high
      resolution CT (HRCT) scan exclude recognised causes of productive cough but sputum culture is
      often positive for Haemophilus influenzae although sometimes demonstrates normal respiratory
      flora despite being markedly purulent.

      Due to their efficacy in cystic fibrosis and bronchiectasis we have empirically tried
      treatment with low dose macrolide antibiotics over 3-6 months often with dramatic benefit.
      This is however an unproven and unlicensed indication which needs to be more thoroughly
      evaluated.

      The key objective of the study is to determine if 12 weeks treatment of patients with chronic
      productive cough with low dose azithromycin is both effective and safe.

      The secondary objectives of the study are to describe the clinical and pathological features
      of a cohort of patients who present with chronic productive cough (with no evidence of
      bronchiectasis, smoking-related chronic bronchitis or immunodeficiency) to determine if these
      are sufficiently similar to justify a new diagnostic label.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in cough on the Leicester Cough Questionnaire (LCQ) score at week 12
time frame: 12 weeks after treatment started
measure: Change from baseline in sputum colour (as per previously validated commercially available graded sputum colour chart) at week 12
time frame: 12 weeks after treatment started
measure: Change from baseline in exhaled nitric oxide level (ppm) at week 24
time frame: 12 weeks after treatment started
measure: Change from baseline in FEV1 (ml) at week 24
time frame: 12 weeks after treatment started
measure: Change from baseline in sputum volume (ml) at week 12
time frame: 12 weeks after treatment started
arm group label: Azithromycin
arm group type: Experimental
description: 250mg azithromycin three times weekly for 12 weeks
intervention type: Drug
intervention name: Azithromycin
description: 250mg azithromycin three times per week for 12 weeks
arm group label: Azithromycin
other name: Zithromax
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Tim Harrison, MD, FRCP
role: Principal Investigator
affiliation: University of Nottingham
last name: Matthew Martin, MBChB
phone: 01158231935
email: matthew.martin@nottingham.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cough
mesh term: Azithromycin
sharing ipd: No