<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/NCT04503460</url>
  </required_header>
  <id_info>
    <org_study_id>19SM5101</org_study_id>
    <secondary_id>2019-003036-23</secondary_id>
    <nct_id>NCT04503460</nct_id>
  </id_info>
  <brief_title>Mechanisms of Adverse Effects of Long-Acting Beta-Agonists in Asthma</brief_title>
  <acronym>MAELABA</acronym>
  <official_title>Mechanisms of Adverse Effects of Long-Acting Beta-Agonists in Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</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 study aims to elucidate the pathophysiological mechanisms underlying the adverse effects&#xD;
      associated with the use of long-acting beta-agonists (LABAs) in asthma. Participants with&#xD;
      mild asthma will be enrolled into a single-arm, unblinded trial in which they receive 2 weeks&#xD;
      of salmeterol xinafoate monotherapy, followed by a 2-week washout period, followed by 2 weeks&#xD;
      of salmeterol xinafoate / fluticasone propionate combination therapy. The induction of asthma&#xD;
      disease-relevant pro-inflammatory mediators in the airways will be measured at each stage and&#xD;
      correlated with relevant clinical parameters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The use of long-acting beta-agonists (LABAs) alone to treat asthma has been associated with&#xD;
      increased mortality rates. Between 2012 and 2013, 3% of patients who died from asthma in the&#xD;
      UK were found to be on LABA monotherapy, despite guidelines recommending that LABAs must&#xD;
      always be administered with inhaled corticosteroids (ICS). Monotherapy with the LABA&#xD;
      salmeterol has been linked to a significant increase in asthma-related mortality rates when&#xD;
      used without ICS. When salmeterol is used with ICS, it is not associated with an increased&#xD;
      risk of serious asthma-related events and is associated with fewer exacerbations than when&#xD;
      using ICS alone. The purpose of this study is to understand the mechanisms underlying why&#xD;
      LABA use on its own causes worse outcomes in asthma patients. If the mechanisms can be&#xD;
      successfully understood, this could provide further compelling evidence to optimise safe of&#xD;
      these medicines in airway disease.&#xD;
&#xD;
      The primary objective of this study will be: to determine whether LABA monotherapy with&#xD;
      salmeterol for 2 weeks in asthmatic patients induces disease-relevant mediators (as&#xD;
      identified through ex vivo studies) in the airways in vivo; and to determine whether LABA/ICS&#xD;
      combination therapy with salmeterol xinafoate/fluticasone propionate for 2 weeks in the same&#xD;
      asthmatic patients will abolish the induction of disease-relevant mediators in the airways in&#xD;
      vivo. If it can be shown that the levels of these inflammatory mediators increase in the&#xD;
      airways of asthmatic patients when they are on salmeterol xinafoate monotherapy, and that&#xD;
      this effect is decreased when asthmatic patients are on salmeterol xinafoate /fluticasone&#xD;
      propionate combination therapy, this will provide evidence for a mechanism underlying the&#xD;
      adverse effects of salmeterol in asthmatic patients.&#xD;
&#xD;
      Secondary objectives will be to determine the impact of LABA monotherapy with salmeterol&#xD;
      xinafoate for 2 weeks and LABA/ICS therapy with salmeterol xinafoate/fluticasone propionate&#xD;
      for 2 weeks on the following parameters in asthmatic patients: lung function (assessed by&#xD;
      spirometry); airway inflammation (assessed by measuring fractional exhaled nitric oxide);&#xD;
      airway hyperresponsiveness (assessed by histamine challenge testing); asthma symptom control&#xD;
      (assessed by the Asthma Control Questionnaire-6); and serum brain-derived neurotrophic factor&#xD;
      (BDNF) concentration and platelet BDNF concentration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 23, 2021</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>All participants will receive salmeterol xinafoate monotherapy for 2 weeks, followed by a washout period for 2 weeks, followed by salmeterol xinafoate/fluticasone propionate combination therapy for 2 weeks.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>1. Pro-inflammatory mediator protein expression following salmeterol monotherapy</measure>
    <time_frame>[Time Frame: Change between Day 1 (baseline bronchoscopy) and Day 15 (post-salmeterol monotherapy bronchoscopy)]</time_frame>
    <description>Change from baseline in the level of disease-relevant pro-inflammatory mediator IL-6 in Bronchoalveolar Lavage (BAL) fluid following 2 weeks of salmeterol monotherapy.</description>
  </primary_outcome>
  <other_outcome>
    <measure>1. Pro-inflammatory mediator gene expression following salmeterol monotherapy</measure>
    <time_frame>[Time Frame: Change between Day 1 (baseline bronchoscopy) and Day 15 (post-salmeterol monotherapy bronchoscopy)]</time_frame>
    <description>Change from baseline in the levels of gene expression of disease-relevant pro-inflammatory mediators in BAL fluid following 2 weeks of salmeterol monotherapy.</description>
  </other_outcome>
  <other_outcome>
    <measure>2. Pro-inflammatory mediator protein expression following salmeterol/fluticasone combination therapy</measure>
    <time_frame>[Time Frame: Change between Day 29 (post-salmeterol washout bronchoscopy) and Day 43 (post salmeterol/fluticasone combination therapy bronchoscopy)]</time_frame>
    <description>Change from baseline in protein levels of disease-relevant pro-inflammatory mediators in BAL fluid following 2 weeks of salmeterol/fluticasone combination therapy</description>
  </other_outcome>
  <other_outcome>
    <measure>3. Pro-inflammatory mediator gene expression following salmeterol/fluticasone combination therapy</measure>
    <time_frame>[Time Frame: Change between Day 29 (post-salmeterol washout bronchoscopy) and Day 43 (post salmeterol/fluticasone combination therapy bronchoscopy)]</time_frame>
    <description>Change from baseline in the levels of gene expression of disease-relevant pro-inflammatory mediators in BAL fluid following 2 weeks of salmeterol/fluticasone combination therapy</description>
  </other_outcome>
  <other_outcome>
    <measure>4. Lung function (spirometry)</measure>
    <time_frame>[Time Frame: Over 7 weeks]</time_frame>
    <description>Change in lung function, measured by spirometry, between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy</description>
  </other_outcome>
  <other_outcome>
    <measure>5. Fractional exhaled nitric oxide</measure>
    <time_frame>[Time Frame: Over 7 weeks]</time_frame>
    <description>Change in fractional exhaled nitric oxide between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy</description>
  </other_outcome>
  <other_outcome>
    <measure>6. Airway hyperresponsiveness (histamine challenge)</measure>
    <time_frame>[Time Frame: Over 7 weeks]</time_frame>
    <description>Change in airway hyperresponsiveness, measured by histamine challenge, between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy</description>
  </other_outcome>
  <other_outcome>
    <measure>7. Asthma symptom control (Asthma Control Questionnaire 6 / ACQ-6 score)</measure>
    <time_frame>[Time Frame: Over 7 weeks]</time_frame>
    <description>Change in asthma symptom control, measured by ACQ-6 scoring, between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy. ACQ-6 is a validated tool for assessing patients' perceived degree of severity and symptom control of their asthma. The questionnaire comprises of 6 multiple choice questions, each with 7 possible choices (only one selectable) carrying scores between 0 and 6 - total added ACQ-6 score ranges between 0 and 36, with a score of 36 representing the highest possible symptom burden measured by this questionnaire.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Single treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants who are deemed eligible for inclusion in the study following screening will be enrolled into a single experimental arm which will comprise the following sequential stages:&#xD;
Baseline sampling; participants only use 'as required' ipratropium bromide when needed (1 week)&#xD;
Salmeterol xinafoate monotherapy 50 μg twice in the morning and twice in the evening + 'as required' ipratropium bromide when needed (2 weeks)&#xD;
Washout period; participants only use 'as required' ipratropium bromide when needed (2 weeks)&#xD;
Salmeterol xinafoate 50 μg / fluticasone propionate 250 μg combination therapy twice in the morning and twice in the evening + 'as required' ipratropium bromide when needed (2 weeks)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol Xinafoate</intervention_name>
    <description>All participants will receive inhaled salmeterol xinafoate 50 μg twice in the morning and twice in the evening for 2 weeks; this will be followed by a 2-week washout period during which time no beta-agonists will be administered. Participants will be asked to use 'as required' ipratropium bromide during this period when needed in place of short-acting beta agonists.</description>
    <arm_group_label>Single treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol Fluticasone</intervention_name>
    <description>Following the 2-week washout period, all participants will receive inhaled salmeterol xinafoate 50 μg combined with fluticasone propionate 250 μg twice in the morning and twice in the evening for 2 weeks. Participants will be asked to use 'as required' ipratropium bromide during this period when needed in place of short-acting beta agonists.</description>
    <arm_group_label>Single treatment arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  A doctor's diagnosis of asthma (mild in severity)&#xD;
&#xD;
          -  No current regular asthma treatment or regular asthma treatment in the preceding 6&#xD;
             weeks; only a history of using short-acting bronchodilator inhalers on demand is&#xD;
             allowed&#xD;
&#xD;
          -  Pre-bronchodilator FEV1 value &gt; 70% of the predicted value&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          -  History or evidence of chronic respiratory disease other than asthma&#xD;
&#xD;
          -  History or evidence of other disease, blood test results outside the normal reference&#xD;
             range or medication use that would impair the ability of participants to safely&#xD;
             undertake the study or the ability of researchers to interpret the study results; this&#xD;
             includes, but is not limited to, the use of anticoagulants (e.g. warfarin), adenosine&#xD;
             diphosphate (ADP) receptor inhibitors (e.g. clopidogrel), antiretroviral therapy (due&#xD;
             to the potential for interaction with fluticasone), certain antifungal agents (due to&#xD;
             the potential for interaction with fluticasone) and beta-blockers&#xD;
&#xD;
          -  Current use or use in the last 6 weeks of systemic or nasal topical steroids, inhaled&#xD;
             corticosteroids or systemic immunosuppressants&#xD;
&#xD;
          -  Platelet count &lt; 150 x 109/L or international normalised ratio (INR) &gt; 1.5&#xD;
&#xD;
          -  History of smoking &gt; 5 pack years, current smoker or history of smoking in the last 4&#xD;
             weeks&#xD;
&#xD;
          -  Current vaping or history of vaping in the last 4 weeks&#xD;
&#xD;
          -  Current illicit drug use/abuse&#xD;
&#xD;
          -  Abnormal chest x-ray appearance&#xD;
&#xD;
          -  Signs or symptoms of upper respiratory tract infection or lower respiratory tract&#xD;
             infection in the preceding 6 weeks&#xD;
&#xD;
          -  Cardiac conduction abnormalities on electrocardiogram (ECG)&#xD;
&#xD;
          -  Current pregnancy or planning to become pregnant during the study period&#xD;
&#xD;
          -  Breastfeeding during the study period&#xD;
&#xD;
          -  Inability to provide informed consent to participate in the study&#xD;
&#xD;
          -  Current involvement in any other clinical research studies involving medicinal&#xD;
             products or devices; or involvement in clinical research studies involving medicinal&#xD;
             products within the last 30 days or within 5 half-lives of the medicinal product&#xD;
             (whichever is longer)&#xD;
&#xD;
          -  Inability to speak English or inability to understand verbal or written English&#xD;
&#xD;
          -  Inability to attend hospital for all scheduled study visits&#xD;
&#xD;
          -  Hypersensitivity to any of the investigational medicinal products (IMPs) or their&#xD;
             excipients&#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>Sebastian L Johnston, MBBS PhD FRCP FRSB FMedSci</last_name>
    <role>Study Chair</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sebastian L Johnston, MBBS PhD FRCP FRSB FMedSci</last_name>
    <phone>+44 20 7594 3764</phone>
    <email>s.johnston@imperial.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eva Fiorenzo, BMBS</last_name>
    <phone>+44 20 7594 3751</phone>
    <email>e.fiorenzo@imperial.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>St Mary's Hospital, Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W2 1NY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sebastian L Johnston, MBBS PhD FRCP FRSB FMedSci</last_name>
      <phone>+44 20 7594 3764</phone>
      <email>s.johnston@imperial.ac.uk</email>
    </contact>
    <contact_backup>
      <last_name>Pil Joo Kim, BSc RGN</last_name>
      <phone>+44 7900883689</phone>
      <email>piljoo.kim@nhs.net</email>
    </contact_backup>
    <investigator>
      <last_name>Sebastian L Johnston, MBBS PhD FRCP FRSB FMedSci</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Aran Singanayagam, MBChB PhD MRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patrick Mallia, MD PhD FRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Onn Min Kon, MD FRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 1, 2019</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>April 21, 2023</last_update_submitted>
  <last_update_submitted_qc>April 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Asthma</keyword>
  <keyword>Salmeterol</keyword>
  <keyword>Fluticasone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
    <mesh_term>Fluticasone-Salmeterol Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymised study data to be stored in an online repository for potential future sharing with other researchers. Current protocol and other related documents are undergoing amendments in order to include this plan.</ipd_description>
  </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/NCT04503460
org study id: 19SM5101
secondary id: 2019-003036-23
nct id: NCT04503460
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study aims to elucidate the pathophysiological mechanisms underlying the adverse effects
      associated with the use of long-acting beta-agonists (LABAs) in asthma. Participants with
      mild asthma will be enrolled into a single-arm, unblinded trial in which they receive 2 weeks
      of salmeterol xinafoate monotherapy, followed by a 2-week washout period, followed by 2 weeks
      of salmeterol xinafoate / fluticasone propionate combination therapy. The induction of asthma
      disease-relevant pro-inflammatory mediators in the airways will be measured at each stage and
      correlated with relevant clinical parameters.
The use of long-acting beta-agonists (LABAs) alone to treat asthma has been associated with
      increased mortality rates. Between 2012 and 2013, 3% of patients who died from asthma in the
      UK were found to be on LABA monotherapy, despite guidelines recommending that LABAs must
      always be administered with inhaled corticosteroids (ICS). Monotherapy with the LABA
      salmeterol has been linked to a significant increase in asthma-related mortality rates when
      used without ICS. When salmeterol is used with ICS, it is not associated with an increased
      risk of serious asthma-related events and is associated with fewer exacerbations than when
      using ICS alone. The purpose of this study is to understand the mechanisms underlying why
      LABA use on its own causes worse outcomes in asthma patients. If the mechanisms can be
      successfully understood, this could provide further compelling evidence to optimise safe of
      these medicines in airway disease.

      The primary objective of this study will be: to determine whether LABA monotherapy with
      salmeterol for 2 weeks in asthmatic patients induces disease-relevant mediators (as
      identified through ex vivo studies) in the airways in vivo; and to determine whether LABA/ICS
      combination therapy with salmeterol xinafoate/fluticasone propionate for 2 weeks in the same
      asthmatic patients will abolish the induction of disease-relevant mediators in the airways in
      vivo. If it can be shown that the levels of these inflammatory mediators increase in the
      airways of asthmatic patients when they are on salmeterol xinafoate monotherapy, and that
      this effect is decreased when asthmatic patients are on salmeterol xinafoate /fluticasone
      propionate combination therapy, this will provide evidence for a mechanism underlying the
      adverse effects of salmeterol in asthmatic patients.

      Secondary objectives will be to determine the impact of LABA monotherapy with salmeterol
      xinafoate for 2 weeks and LABA/ICS therapy with salmeterol xinafoate/fluticasone propionate
      for 2 weeks on the following parameters in asthmatic patients: lung function (assessed by
      spirometry); airway inflammation (assessed by measuring fractional exhaled nitric oxide);
      airway hyperresponsiveness (assessed by histamine challenge testing); asthma symptom control
      (assessed by the Asthma Control Questionnaire-6); and serum brain-derived neurotrophic factor
      (BDNF) concentration and platelet BDNF concentration.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: All participants will receive salmeterol xinafoate monotherapy for 2 weeks, followed by a washout period for 2 weeks, followed by salmeterol xinafoate/fluticasone propionate combination therapy for 2 weeks.
primary purpose: Basic Science
masking: None (Open Label)
measure: 1. Pro-inflammatory mediator protein expression following salmeterol monotherapy
time frame: [Time Frame: Change between Day 1 (baseline bronchoscopy) and Day 15 (post-salmeterol monotherapy bronchoscopy)]
description: Change from baseline in the level of disease-relevant pro-inflammatory mediator IL-6 in Bronchoalveolar Lavage (BAL) fluid following 2 weeks of salmeterol monotherapy.
measure: 1. Pro-inflammatory mediator gene expression following salmeterol monotherapy
time frame: [Time Frame: Change between Day 1 (baseline bronchoscopy) and Day 15 (post-salmeterol monotherapy bronchoscopy)]
description: Change from baseline in the levels of gene expression of disease-relevant pro-inflammatory mediators in BAL fluid following 2 weeks of salmeterol monotherapy.
measure: 2. Pro-inflammatory mediator protein expression following salmeterol/fluticasone combination therapy
time frame: [Time Frame: Change between Day 29 (post-salmeterol washout bronchoscopy) and Day 43 (post salmeterol/fluticasone combination therapy bronchoscopy)]
description: Change from baseline in protein levels of disease-relevant pro-inflammatory mediators in BAL fluid following 2 weeks of salmeterol/fluticasone combination therapy
measure: 3. Pro-inflammatory mediator gene expression following salmeterol/fluticasone combination therapy
time frame: [Time Frame: Change between Day 29 (post-salmeterol washout bronchoscopy) and Day 43 (post salmeterol/fluticasone combination therapy bronchoscopy)]
description: Change from baseline in the levels of gene expression of disease-relevant pro-inflammatory mediators in BAL fluid following 2 weeks of salmeterol/fluticasone combination therapy
measure: 4. Lung function (spirometry)
time frame: [Time Frame: Over 7 weeks]
description: Change in lung function, measured by spirometry, between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy
measure: 5. Fractional exhaled nitric oxide
time frame: [Time Frame: Over 7 weeks]
description: Change in fractional exhaled nitric oxide between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy
measure: 6. Airway hyperresponsiveness (histamine challenge)
time frame: [Time Frame: Over 7 weeks]
description: Change in airway hyperresponsiveness, measured by histamine challenge, between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy
measure: 7. Asthma symptom control (Asthma Control Questionnaire 6 / ACQ-6 score)
time frame: [Time Frame: Over 7 weeks]
description: Change in asthma symptom control, measured by ACQ-6 scoring, between baseline and following 2 weeks of salmeterol monotherapy; and between post-salmeterol washout baseline and following 2 weeks salmeterol/fluticasone combination therapy. ACQ-6 is a validated tool for assessing patients' perceived degree of severity and symptom control of their asthma. The questionnaire comprises of 6 multiple choice questions, each with 7 possible choices (only one selectable) carrying scores between 0 and 6 - total added ACQ-6 score ranges between 0 and 36, with a score of 36 representing the highest possible symptom burden measured by this questionnaire.
arm group label: Single treatment arm
arm group type: Experimental
description: All participants who are deemed eligible for inclusion in the study following screening will be enrolled into a single experimental arm which will comprise the following sequential stages:
Baseline sampling; participants only use 'as required' ipratropium bromide when needed (1 week)
Salmeterol xinafoate monotherapy 50 μg twice in the morning and twice in the evening + 'as required' ipratropium bromide when needed (2 weeks)
Washout period; participants only use 'as required' ipratropium bromide when needed (2 weeks)
Salmeterol xinafoate 50 μg / fluticasone propionate 250 μg combination therapy twice in the morning and twice in the evening + 'as required' ipratropium bromide when needed (2 weeks)
intervention type: Drug
intervention name: Salmeterol Xinafoate
description: All participants will receive inhaled salmeterol xinafoate 50 μg twice in the morning and twice in the evening for 2 weeks; this will be followed by a 2-week washout period during which time no beta-agonists will be administered. Participants will be asked to use 'as required' ipratropium bromide during this period when needed in place of short-acting beta agonists.
arm group label: Single treatment arm
intervention type: Drug
intervention name: Salmeterol Fluticasone
description: Following the 2-week washout period, all participants will receive inhaled salmeterol xinafoate 50 μg combined with fluticasone propionate 250 μg twice in the morning and twice in the evening for 2 weeks. Participants will be asked to use 'as required' ipratropium bromide during this period when needed in place of short-acting beta agonists.
arm group label: Single treatment arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sebastian L Johnston, MBBS PhD FRCP FRSB FMedSci
role: Study Chair
affiliation: Imperial College London
last name: Sebastian L Johnston, MBBS PhD FRCP FRSB FMedSci
phone: +44 20 7594 3764
email: s.johnston@imperial.ac.uk
last name: Eva Fiorenzo, BMBS
phone: +44 20 7594 3751
email: e.fiorenzo@imperial.ac.uk
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Asthma
mesh term: Fluticasone
mesh term: Salmeterol Xinafoate
mesh term: Fluticasone-Salmeterol Drug Combination
sharing ipd: Yes
ipd description: Anonymised study data to be stored in an online repository for potential future sharing with other researchers. Current protocol and other related documents are undergoing amendments in order to include this plan.