<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/NCT04458636</url>
  </required_header>
  <id_info>
    <org_study_id>17/LO/1135</org_study_id>
    <nct_id>NCT04458636</nct_id>
  </id_info>
  <brief_title>Stratified TreAtment to Reduce Risk in COPD</brief_title>
  <acronym>STARR2</acronym>
  <official_title>Delivering Personalised Care in the Management of Exacerbations of Chronic Obstructive Pulmonary Disease: A Multi-centre Randomised Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</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>
      To evaluate the efficacy of blood-eosinophil directed corticosteroid therapy using&#xD;
      near-patient testing, compared to current standard practice during an exacerbation of COPD in&#xD;
      a multi-centre randomised placebo controlled trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design: Double-blind placebo controlled randomised clinical trial Study setting:&#xD;
      Primary care GP practices Participants: Adults ≥40 years with COPD Sample size: 228 Study&#xD;
      duration: 12 months data collection Primary objective: To evaluate the efficacy of&#xD;
      blood-eosinophil directed corticosteroid therapy using near-patient testing, compared to&#xD;
      current standard practice during an exacerbation of COPD.&#xD;
&#xD;
      Secondary objective: To evaluate quality of life, symptoms, lung function and healthcare&#xD;
      utilisation in a blood-eosinophil directed corticosteroid therapy arm.&#xD;
&#xD;
      Exploratory objective: To evaluate stability of eosinophil counts and mediator levels&#xD;
&#xD;
      Chronic obstructive pulmonary disease (COPD) affects adults and is largely caused by&#xD;
      cigarette smoke in the developed world. It is predicted to be the 3rd leading cause of death&#xD;
      by 2020 affecting over 250 million people worldwide. COPD is characterised by progressive&#xD;
      airflow obstruction punctuated by frequent periods of worsening in respiratory symptoms and&#xD;
      function associated with a significant impact on quality of life. These episodes are termed&#xD;
      exacerbations and current treatment strategies rely on oral corticosteroids (prednisolone)&#xD;
      and antibiotics but this is in a &quot;one size fits all&quot; approach. However there is little&#xD;
      evidence supporting this strategy and both treatments can potentially cause harm. In addition&#xD;
      to this, previous findings have shown that eosinophil counts within blood samples from COPD&#xD;
      patients can be used as a biomarker to determine treatment with oral steroids.&#xD;
&#xD;
      The use of near-patient testing in primary care will characterise patients with COPD and&#xD;
      inform to guide effective and personalised treatment with reductions in treatment failure&#xD;
      rates, improvements in health and reductions in adverse events associated with inappropriate&#xD;
      and excessive corticosteroid and antibiotic therapy. Currently available systems include the&#xD;
      HemoCue ® 5-point differential cell count system which accurately and rapidly (within 2&#xD;
      minutes) determine the eosinophil count finger-prick sampling. This diagnostic is currently&#xD;
      used in neonatology, Emergency Departments (ED) and at Mount Everest Base Camp 28-30. It is&#xD;
      thus conceivable that this could be used in primary care to deliver a randomised control&#xD;
      trial to demonstrate that stratified medicine approaches in the management of COPD&#xD;
      exacerbations are superior to standard therapy.&#xD;
&#xD;
      It is believed that personalising this treatment approach during an exacerbation of COPD, to&#xD;
      direct whether corticosteroids is necessary for all patients, depending on the results of the&#xD;
      eosinophil count from near-patient testing, is superior to current standard treatment&#xD;
      strategies in the primary care setting.&#xD;
&#xD;
      Recruitment target for STARR 2 is 228 participants with COPD from GP surgeries within the&#xD;
      Thames Valley and South Midlands. A participant's involvement is 12 months and involves up to&#xD;
      5 visits. These visits consist of CRF completion, questionnaires, breathing tests, urine&#xD;
      testing, blood samples and spirometry. The trial drugs are only taken for 14 days during an&#xD;
      exacerbation but participants can be re-randomised for up to 4 times in the study when they&#xD;
      exacerbate.&#xD;
&#xD;
      Intervention: At exacerbation randomised to 'standard therapy' or 'blood eosinophil directed&#xD;
      therapy'. Standard therapy will be prednisolone and antibiotic therapy. Blood eosinophil&#xD;
      directed therapy will be prednisolone and/or antibiotic therapy.&#xD;
&#xD;
      Investigational medicinal product: Prednisolone or placebo equivalent. The IMP is part of&#xD;
      current clinical practice. Prednisolone is an anti-inflammatory and given in short durations&#xD;
      (≤2 weeks duration) orally for its systemic action at the onset of an exacerbation in COPD.&#xD;
&#xD;
      Participation duration: Study entry at stable state or during an exacerbation. Randomisation&#xD;
      at exacerbation. IMP treatment period 14 days. Post treatment follow-up visits at days 14, 30&#xD;
      and 90. Stable state and randomisation visit duration maximum 60 minutes. Follow-up visits at&#xD;
      days 14, 30, and 90 maximum duration 30 minutes. Participants may be re-randomised and&#xD;
      followed up if they have further exacerbations after the 30 day visit.&#xD;
&#xD;
      Data collection: Demographic and exacerbation clinical data including duration of symptoms,&#xD;
      past medical history, medication history and exacerbation history is collected. Blood&#xD;
      eosinophil tests is collected by pin-prick testing using the HemoCue ®; lung function using&#xD;
      spirometry and FeNO; and symptoms and quality of life using questionnaires. Serum is&#xD;
      collected at visits.&#xD;
&#xD;
      Study schedule:&#xD;
&#xD;
      Study assessments will be performed within primary care by the research study team. The&#xD;
      following assessments may occur at the study visits:&#xD;
&#xD;
      Eligibility check: Inclusion and exclusion criteria will be checked against the participant's&#xD;
      medical notes and with the participant during the visit. This responsibility will be&#xD;
      delegated by the PI to a member of the research team.&#xD;
&#xD;
      Demographic history: Participant demographics including age, smoking history and past COPD&#xD;
      medical history will be collected.&#xD;
&#xD;
      Medication history: Full medication history will be collected, including the use of as&#xD;
      required and over the counter medication. Any drug allergy will be documented and dates of&#xD;
      flu vaccination, S. pneumoniae and H. influenzae B vaccinations will be recorded from medical&#xD;
      records.&#xD;
&#xD;
      Past medical history: Full medical history will be collected from the participant and from&#xD;
      the medical notes. COPD diagnosis history: The age of onset and age of diagnosis of COPD&#xD;
      symptoms will be recorded from the participant and from the medical records.&#xD;
&#xD;
      Past exacerbation history: The frequency of exacerbations, including those requiring&#xD;
      hospitalisation in the previous 12 months will be captured from participant recollection and&#xD;
      from the medical records. Medication prescribed at each exacerbation event (if available)&#xD;
      from medical records will be captured.&#xD;
&#xD;
      Exacerbation history: The current history of the exacerbation, including duration of symptoms&#xD;
      and treatment history will collected by questioning. The severity of the exacerbation will be&#xD;
      recorded according to Anthonisen criteria14 with increased symptoms of breathlessness, sputum&#xD;
      production and sputum purulence will be used as per GOLD31 definition. The Anthonisen&#xD;
      criteria for exacerbation as follows: Type 1 - Three major symptoms; Type 2 - two major&#xD;
      symptoms; Type 3 - One major and one minor symptom. The major symptoms are i) Increased&#xD;
      breathlessness; ii) increased sputum production; or iii) increased sputum purulence. The&#xD;
      minor symptoms are iv) Upper respiratory tract infection in the previous 5 days; v) fever&#xD;
      without apparent cause; vi) increased wheeze; vii) increased cough; viii) increase in&#xD;
      respiratory or heart rate 20% above baseline. Questionnaires: Patient reported outcome&#xD;
      measures (PRO's) will be sought to specifically test symptoms, health status, quality of life&#xD;
      and any associated depression and anxiety. This will include the Medical Research Council&#xD;
      dyspnoea scale (MRC); Visual analogue score (VAS) 32; COPD Assessment Tool (CAT) 33; the&#xD;
      Hospital Anxiety and Depression Scale (HADS)34 and the EuroQol 5D35. Participants will be&#xD;
      asked to complete a daily diary (using the VAS tool, for the duration of 30 days) for&#xD;
      assessment of symptoms and recovery following treatment. Instructions to use these&#xD;
      questionnaires will be given to all participants. Each of these questionnaires are validated&#xD;
      to be self-completed for ease of use. All research staff undertaking any assessments and&#xD;
      procedures will be trained to use the equipment and perform the questionnaires to determine&#xD;
      patient reported outcomes. Near-patient point of care testing procedures:&#xD;
&#xD;
      Approximately 5 drops of blood (up to a maximum of 10 drops) will be taken for measurement of&#xD;
      peripheral blood eosinophil counts, glucose and CRP levels.&#xD;
&#xD;
      A urine sample for testing of glycosuria will be performed immediately. All samples will be&#xD;
      discarded.&#xD;
&#xD;
      Lung Function: Spirometry will be performed to determine the forced expiratory volume in 1&#xD;
      second (FEV1) and the forced vital capacity (FVC) according to standard ATS/ERS criteria36.&#xD;
&#xD;
      Venous blood sampling: Using a fully sterile technique, a blood test will be performed to&#xD;
      measure inflammation. All participants consenting to trial sample collection will have a&#xD;
      maximum of 20mLs of blood taken at each visit. Collected blood will be centrifuged&#xD;
      immediately and serum/plasma will be aliquoted into fully anonymised barcoded tubes.&#xD;
      Anonymised samples will be then be securely transported to the John Radcliffe Hospital and&#xD;
      stored at the Respiratory Medicine Laboratory (John Radcliffe Hospital), under the HTA&#xD;
      licence, at -80˚c for exploratory outcome analysis and for future use subject to ethical&#xD;
      approval. There will be separate instructions detailing the sample handling process for this&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2017</start_date>
  <completion_date type="Actual">April 30, 2020</completion_date>
  <primary_completion_date type="Actual">February 28, 2020</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of treatment non-responders defined as those needing re-treatment, hospitalisation or death at 30 and 90 days</measure>
    <time_frame>30 days</time_frame>
    <description>Frequency of treatment non-responders, defined as those needing re-treatment, hospitalisation or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>COPD assessment test (CAT)</measure>
    <time_frame>Day 14, 30 and 90</time_frame>
    <description>CAT questionnaire. A higher score (max score of 40) reflects worse COPD symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life - change from baseline</measure>
    <time_frame>Day 14, 30 and 90</time_frame>
    <description>European Quality of Life-5 dimension-3 level (EQ 5D 3L) questionnaire. A higher number on each of the 5 dimension reflects worse quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual analogue scale (VAS) for cough, wheeze, sputum volume, sputum purulence and breathlessness</measure>
    <time_frame>Day 14, 30 and 90</time_frame>
    <description>Visual Analogue Scale (VAS) symptom score (scale of 0 to 100 - 100 being the worst). Separate scale for 5 items: cough, wheeze, sputum volume, sputum purulence and breathlessness. Results will be represented as a sum of all 5 scores at each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function</measure>
    <time_frame>Day 14, 30 and 90</time_frame>
    <description>Change from baseline in FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exacerbations</measure>
    <time_frame>12 months</time_frame>
    <description>Frequency of moderate and severe exacerbations</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">203</enrollment>
  <condition>COPD Exacerbation</condition>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Blinded prednisolone 30mg orally once per day for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Biomarker care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Blinded prednisolone 30mg orally once per day for 14 days if peripheral eosinophil count is equal or greater than 2%. Placebo equivalent if peripheral blood eosinophil count is &lt;2%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone</intervention_name>
    <description>Oral</description>
    <arm_group_label>Biomarker care</arm_group_label>
    <arm_group_label>Standard care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is willing and able to give informed consent for participation in the&#xD;
             trial.&#xD;
&#xD;
          -  Male or Female, aged 40 years or above.&#xD;
&#xD;
          -  Diagnosed with COPD (primary or secondary care diagnosis) with spirometric&#xD;
             confirmation of airflow obstruction (FEV1/FVC ratio &lt;0.7).&#xD;
&#xD;
          -  A history of at least 1 exacerbation in the previous 12 months, requiring systemic&#xD;
             corticosteroids and/or antibiotics.&#xD;
&#xD;
          -  Current or ex-smoker with at least a 10 pack year smoking history&#xD;
&#xD;
          -  In the opinion of the research staff, is able and willing to comply with all trial&#xD;
             requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of atopic childhood asthma&#xD;
&#xD;
          -  Current history of primary lung malignancy or current active pulmonary TB&#xD;
&#xD;
          -  Clinically relevant disease or disorder (past or present) which in the opinion of the&#xD;
             investigator may either put the subject at risk because of participating in the study&#xD;
             or may influence the results of the study or the subject's ability to participate in&#xD;
             the study.&#xD;
&#xD;
          -  Any clinically relevant lung disease, other than COPD considered by the investigator&#xD;
             to be the primary diagnosis. For example mild-to-moderate bronchiectasis is acceptable&#xD;
             in addition to COPD unless the bronchiectasis is considered to be the primary&#xD;
             diagnosis.&#xD;
&#xD;
          -  An alternative cause for the increase in symptoms of COPD that are unrelated to an&#xD;
             exacerbation such as i) suspicion or clinical evidence of pneumonia; ii) high&#xD;
             probability and suspicion of pulmonary embolism; iii) suspicion or clinical evidence&#xD;
             of a pneumothorax; iv) primary ischaemic event - ST or Non ST elevation myocardial&#xD;
             infarct and left ventricular failure [i.e. not an exacerbation of COPD]&#xD;
&#xD;
          -  A known allergy to the IMP (prednisolone), NIMP (doxycycline) or to any of the&#xD;
             constituents of the placebo&#xD;
&#xD;
          -  Patients on maintenance corticosteroids (prednisolone, hydrocortisone,&#xD;
             fludrocortisone)&#xD;
&#xD;
          -  Known adrenal insufficiency&#xD;
&#xD;
          -  Currently enrolled in another CTIMP trial and receiving an intervention as part of the&#xD;
             trial.&#xD;
&#xD;
          -  Pregnant and breast-feeding women&#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>Mona Bafadhel, MBChB, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nuffield Department of Medicine</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>https://www.ndm.ox.ac.uk/principal-investigators/researcher/mona-bafadhel</url>
    <description>Website address for CI</description>
  </link>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 20, 2017</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>July 17, 2020</last_update_submitted>
  <last_update_submitted_qc>July 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Oxford</investigator_affiliation>
    <investigator_full_name>Mona Bafadhel</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>eosinophils</keyword>
  <keyword>oral corticosteroids</keyword>
  <keyword>primary care</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisolone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>upon request</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/NCT04458636
org study id: 17/LO/1135
nct id: NCT04458636
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To evaluate the efficacy of blood-eosinophil directed corticosteroid therapy using
      near-patient testing, compared to current standard practice during an exacerbation of COPD in
      a multi-centre randomised placebo controlled trial.
Study design: Double-blind placebo controlled randomised clinical trial Study setting:
      Primary care GP practices Participants: Adults ≥40 years with COPD Sample size: 228 Study
      duration: 12 months data collection Primary objective: To evaluate the efficacy of
      blood-eosinophil directed corticosteroid therapy using near-patient testing, compared to
      current standard practice during an exacerbation of COPD.

      Secondary objective: To evaluate quality of life, symptoms, lung function and healthcare
      utilisation in a blood-eosinophil directed corticosteroid therapy arm.

      Exploratory objective: To evaluate stability of eosinophil counts and mediator levels

      Chronic obstructive pulmonary disease (COPD) affects adults and is largely caused by
      cigarette smoke in the developed world. It is predicted to be the 3rd leading cause of death
      by 2020 affecting over 250 million people worldwide. COPD is characterised by progressive
      airflow obstruction punctuated by frequent periods of worsening in respiratory symptoms and
      function associated with a significant impact on quality of life. These episodes are termed
      exacerbations and current treatment strategies rely on oral corticosteroids (prednisolone)
      and antibiotics but this is in a "one size fits all" approach. However there is little
      evidence supporting this strategy and both treatments can potentially cause harm. In addition
      to this, previous findings have shown that eosinophil counts within blood samples from COPD
      patients can be used as a biomarker to determine treatment with oral steroids.

      The use of near-patient testing in primary care will characterise patients with COPD and
      inform to guide effective and personalised treatment with reductions in treatment failure
      rates, improvements in health and reductions in adverse events associated with inappropriate
      and excessive corticosteroid and antibiotic therapy. Currently available systems include the
      HemoCue ® 5-point differential cell count system which accurately and rapidly (within 2
      minutes) determine the eosinophil count finger-prick sampling. This diagnostic is currently
      used in neonatology, Emergency Departments (ED) and at Mount Everest Base Camp 28-30. It is
      thus conceivable that this could be used in primary care to deliver a randomised control
      trial to demonstrate that stratified medicine approaches in the management of COPD
      exacerbations are superior to standard therapy.

      It is believed that personalising this treatment approach during an exacerbation of COPD, to
      direct whether corticosteroids is necessary for all patients, depending on the results of the
      eosinophil count from near-patient testing, is superior to current standard treatment
      strategies in the primary care setting.

      Recruitment target for STARR 2 is 228 participants with COPD from GP surgeries within the
      Thames Valley and South Midlands. A participant's involvement is 12 months and involves up to
      5 visits. These visits consist of CRF completion, questionnaires, breathing tests, urine
      testing, blood samples and spirometry. The trial drugs are only taken for 14 days during an
      exacerbation but participants can be re-randomised for up to 4 times in the study when they
      exacerbate.

      Intervention: At exacerbation randomised to 'standard therapy' or 'blood eosinophil directed
      therapy'. Standard therapy will be prednisolone and antibiotic therapy. Blood eosinophil
      directed therapy will be prednisolone and/or antibiotic therapy.

      Investigational medicinal product: Prednisolone or placebo equivalent. The IMP is part of
      current clinical practice. Prednisolone is an anti-inflammatory and given in short durations
      (≤2 weeks duration) orally for its systemic action at the onset of an exacerbation in COPD.

      Participation duration: Study entry at stable state or during an exacerbation. Randomisation
      at exacerbation. IMP treatment period 14 days. Post treatment follow-up visits at days 14, 30
      and 90. Stable state and randomisation visit duration maximum 60 minutes. Follow-up visits at
      days 14, 30, and 90 maximum duration 30 minutes. Participants may be re-randomised and
      followed up if they have further exacerbations after the 30 day visit.

      Data collection: Demographic and exacerbation clinical data including duration of symptoms,
      past medical history, medication history and exacerbation history is collected. Blood
      eosinophil tests is collected by pin-prick testing using the HemoCue ®; lung function using
      spirometry and FeNO; and symptoms and quality of life using questionnaires. Serum is
      collected at visits.

      Study schedule:

      Study assessments will be performed within primary care by the research study team. The
      following assessments may occur at the study visits:

      Eligibility check: Inclusion and exclusion criteria will be checked against the participant's
      medical notes and with the participant during the visit. This responsibility will be
      delegated by the PI to a member of the research team.

      Demographic history: Participant demographics including age, smoking history and past COPD
      medical history will be collected.

      Medication history: Full medication history will be collected, including the use of as
      required and over the counter medication. Any drug allergy will be documented and dates of
      flu vaccination, S. pneumoniae and H. influenzae B vaccinations will be recorded from medical
      records.

      Past medical history: Full medical history will be collected from the participant and from
      the medical notes. COPD diagnosis history: The age of onset and age of diagnosis of COPD
      symptoms will be recorded from the participant and from the medical records.

      Past exacerbation history: The frequency of exacerbations, including those requiring
      hospitalisation in the previous 12 months will be captured from participant recollection and
      from the medical records. Medication prescribed at each exacerbation event (if available)
      from medical records will be captured.

      Exacerbation history: The current history of the exacerbation, including duration of symptoms
      and treatment history will collected by questioning. The severity of the exacerbation will be
      recorded according to Anthonisen criteria14 with increased symptoms of breathlessness, sputum
      production and sputum purulence will be used as per GOLD31 definition. The Anthonisen
      criteria for exacerbation as follows: Type 1 - Three major symptoms; Type 2 - two major
      symptoms; Type 3 - One major and one minor symptom. The major symptoms are i) Increased
      breathlessness; ii) increased sputum production; or iii) increased sputum purulence. The
      minor symptoms are iv) Upper respiratory tract infection in the previous 5 days; v) fever
      without apparent cause; vi) increased wheeze; vii) increased cough; viii) increase in
      respiratory or heart rate 20% above baseline. Questionnaires: Patient reported outcome
      measures (PRO's) will be sought to specifically test symptoms, health status, quality of life
      and any associated depression and anxiety. This will include the Medical Research Council
      dyspnoea scale (MRC); Visual analogue score (VAS) 32; COPD Assessment Tool (CAT) 33; the
      Hospital Anxiety and Depression Scale (HADS)34 and the EuroQol 5D35. Participants will be
      asked to complete a daily diary (using the VAS tool, for the duration of 30 days) for
      assessment of symptoms and recovery following treatment. Instructions to use these
      questionnaires will be given to all participants. Each of these questionnaires are validated
      to be self-completed for ease of use. All research staff undertaking any assessments and
      procedures will be trained to use the equipment and perform the questionnaires to determine
      patient reported outcomes. Near-patient point of care testing procedures:

      Approximately 5 drops of blood (up to a maximum of 10 drops) will be taken for measurement of
      peripheral blood eosinophil counts, glucose and CRP levels.

      A urine sample for testing of glycosuria will be performed immediately. All samples will be
      discarded.

      Lung Function: Spirometry will be performed to determine the forced expiratory volume in 1
      second (FEV1) and the forced vital capacity (FVC) according to standard ATS/ERS criteria36.

      Venous blood sampling: Using a fully sterile technique, a blood test will be performed to
      measure inflammation. All participants consenting to trial sample collection will have a
      maximum of 20mLs of blood taken at each visit. Collected blood will be centrifuged
      immediately and serum/plasma will be aliquoted into fully anonymised barcoded tubes.
      Anonymised samples will be then be securely transported to the John Radcliffe Hospital and
      stored at the Respiratory Medicine Laboratory (John Radcliffe Hospital), under the HTA
      licence, at -80˚c for exploratory outcome analysis and for future use subject to ethical
      approval. There will be separate instructions detailing the sample handling process for this
      study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of treatment non-responders defined as those needing re-treatment, hospitalisation or death at 30 and 90 days
time frame: 30 days
description: Frequency of treatment non-responders, defined as those needing re-treatment, hospitalisation or death
measure: COPD assessment test (CAT)
time frame: Day 14, 30 and 90
description: CAT questionnaire. A higher score (max score of 40) reflects worse COPD symptoms
measure: Quality of life - change from baseline
time frame: Day 14, 30 and 90
description: European Quality of Life-5 dimension-3 level (EQ 5D 3L) questionnaire. A higher number on each of the 5 dimension reflects worse quality of life
measure: Visual analogue scale (VAS) for cough, wheeze, sputum volume, sputum purulence and breathlessness
time frame: Day 14, 30 and 90
description: Visual Analogue Scale (VAS) symptom score (scale of 0 to 100 - 100 being the worst). Separate scale for 5 items: cough, wheeze, sputum volume, sputum purulence and breathlessness. Results will be represented as a sum of all 5 scores at each time point.
measure: Lung function
time frame: Day 14, 30 and 90
description: Change from baseline in FEV1
measure: Exacerbations
time frame: 12 months
description: Frequency of moderate and severe exacerbations
arm group label: Standard care
arm group type: Active Comparator
description: Blinded prednisolone 30mg orally once per day for 14 days
arm group label: Biomarker care
arm group type: Placebo Comparator
description: Blinded prednisolone 30mg orally once per day for 14 days if peripheral eosinophil count is equal or greater than 2%. Placebo equivalent if peripheral blood eosinophil count is <2%.
intervention type: Drug
intervention name: Prednisolone
description: Oral
arm group label: Biomarker care
arm group label: Standard care
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Mona Bafadhel, MBChB, PhD
role: Principal Investigator
affiliation: University of Oxford
facility: 
country: United Kingdom
url: https://www.ndm.ox.ac.uk/principal-investigators/researcher/mona-bafadhel
description: Website address for CI
responsible party type: Principal Investigator
investigator affiliation: University of Oxford
investigator full name: Mona Bafadhel
investigator title: Associate Professor
mesh term: Prednisolone
sharing ipd: Undecided
ipd description: upon request