<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/NCT04421742</url>
  </required_header>
  <id_info>
    <org_study_id>9769 del 15.03.2017</org_study_id>
    <nct_id>NCT04421742</nct_id>
  </id_info>
  <brief_title>The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and SAD in COPD Patients.</brief_title>
  <official_title>The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and Dyspnea is Associated to the Improvement in Small Airway Dysfunction in COPD Patients. A Pilot Study (IOSCOPD20161102)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alfredo Antonio Chetta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Parma</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Parma</source>
  <oversight_info>
    <has_dmc>No</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>
      In patients with chronic obstructive pulmonary disease (COPD), small-airway dysfunction (SAD)&#xD;
      is considered a key element and a functional consequence of the pathology. However, the exact&#xD;
      role of SAD as a specific 'pharmacological target' is not yet fully known.&#xD;
&#xD;
      Objectives In an open-label prospective study, we aimed to ascertain whether an extra-fine&#xD;
      formulation of Beclomethasone dipropionate/Formoterol fumarate (BDP/FF) NEXThaler® 100/6 μg&#xD;
      b.i.d. can improve the impact of the disease on the quality of daily life of COPD patients,&#xD;
      acting on SAD.&#xD;
&#xD;
      Methods We studied COPD patients with severe airflow obstruction and 1 moderate exacerbation&#xD;
      in the previous year, being treated with BDP/FF NEXThaler® for 12 weeks. They underwent three&#xD;
      visits, at the start of the treatment (V1), at 6th week (V2) and at 12th week (V3). By the&#xD;
      impulse oscillometry system and by spirometry and plethysmography we measured at each visit&#xD;
      the fall in resistance from 5 to 20 Hz (R5-R20) and the residual volume/total lung capacity&#xD;
      (RV/TLC). COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC)&#xD;
      questionnaire were also measured at each visit to assess the impact of the disease on the&#xD;
      quality of life of the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, there has been a growing interest in deepening the contribution of small&#xD;
      airways (with a diameter &lt;2mm) to the clinical expression of Chronic Obstructive Pulmonary&#xD;
      Disease (COPD).&#xD;
&#xD;
      In patients with stable COPD, SAD severity was found to be progressively increased both with&#xD;
      the degree of airflow obstruction and with GOLD risk class. Moreover, a correlation between&#xD;
      SAD and COPD impact measured with the CAT (COPD Assessment Test) was found, being the&#xD;
      severity of SAD a predictor of the impact of the disease (CAT≥10). A close correlation&#xD;
      between SAD and both quality of life (measured with the St. George's Respiratory&#xD;
      Questionnaire) and perceived dyspnea (measured with the modified Medical Research&#xD;
      Council-mMRC scale) was also found in COPD patients.&#xD;
&#xD;
      The exact role of SAD as a specific 'pharmacological target' is not yet fully known.&#xD;
      According to the guidelines, the administration of combination such as Beclomethasone&#xD;
      dipropionate/Formoterol fumarate (BDP/FF) in extra-fine formulation produced a clinically&#xD;
      relevant improvement in quality of life (&gt; 4 units in the St. George's Respiratory&#xD;
      Questionnaire) and in dyspnea. However, it is not yet defined whether exists a correlation&#xD;
      between symptomatic improvement and SAD and whether an improvement of symptoms can be&#xD;
      achieved acting pharmacologically on SAD.&#xD;
&#xD;
      The rationale for this study is based on the hypothesis that an extra-fine formulation of&#xD;
      BDP/FF, designed to target the entire bronchial three, included the peripheral zone, can&#xD;
      improve the impact of the disease on the quality of life of COPD patients, acting on SAD. The&#xD;
      functional indices of SAD used in this study are from the impulse oscillometry system (IOS),&#xD;
      the standard spirometry and the body plethysmography.&#xD;
&#xD;
      The primary endpoint of the study was, therefore, an improvement of the impact of the disease&#xD;
      on quality of daily life (CAT) and of dyspnea (mMRC) after 12th week treatment with an&#xD;
      extra-fine formulation of BDP/FF in a cohort of COPD patients with severe airway obstruction&#xD;
      and one moderate exacerbation in a previous year; secondary endpoint was an improvement of&#xD;
      the SAD at the 12th week in these patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 31, 2017</start_date>
  <completion_date type="Actual">May 23, 2019</completion_date>
  <primary_completion_date type="Actual">February 8, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change (Improvement) of CAT (Italian version)</measure>
    <time_frame>Change from Baseline CAT at 12th week</time_frame>
    <description>The CAT (COPD Assessment Test) is a questionnaire suitable for completion by all patients diagnosed with COPD. It comprises 8 simple questions that most patients should be able to understand and complete independently.&#xD;
The CAT has a scoring range of 0-40, where each question is ranging 0-5. A CAT score&gt;10 indicates a medium/high impact level of COPD.&#xD;
A difference or change of 2 or more units over 2 to 3 months in a patient suggests a clinically significant difference or change in health status (minimal clinically relevant change, often referred to as the Minimum Clinically Important Difference or MCID).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change (Improvement) of mMRC (Italian version)</measure>
    <time_frame>Change from Baseline mMRC at 12th week</time_frame>
    <description>The modified Medical Research Council (mMRC) dyspnoea scale is a questionnaire that consists of five statements about perceived breathlessness: grade 1, &quot;I only get breathless with strenuous exercise&quot;; grade 2, &quot;I get short of breath when hurrying on the level or up a slight hill&quot;; grade 3, &quot;I walk slower than people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level&quot;; grade 4, &quot;I stop for breath after walking 100 yards or after a few minutes on the level&quot;; grade 5, &quot; I am too breathless to leave the house&quot;. Patients are asked about their perceived breathlessness and are then classified into MRC dyspnoea grades according to how they perceive their disability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change (Improvement) of R5-R20 (kPa x s x L-1)</measure>
    <time_frame>Change from Baseline R5-R20 at 12th week</time_frame>
    <description>The IOS was performed with the Jaeger MasterScreen-IOS device following the standard recommendations. Respiratory resistances at 5 Hz and 20 Hz (R5 and R20, kPa x s x L-1) were used as a total and proximal airway resistance index, respectively, and the resistance drop from 5 to 20 Hz (R5 - R20, kPa x s x L-1) was considered as an indirect index of resistance of the peripheral airways. The oscillometer was calibrated daily.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">43</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>43 COPD</arm_group_label>
    <description>COPD patients with severe airflow obstruction and 1 moderate exacerbation in the previous year being treated with BDP/FF NEXThaler® 100/6 μg b.i.d. for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Beclomethasone Dipropionate/Formoterol Fumarate</intervention_name>
    <description>BDP/FF NEXThaler® 100/6 μg b.i.d.</description>
    <arm_group_label>43 COPD</arm_group_label>
    <other_name>Foster NEXThaler®</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        COPD patients of the outpatient clinic of the Respiratory Disease Unit of the University&#xD;
        Hospital in Parma (Italy)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a documented diagnosis of COPD defined according to the guidelines of the American&#xD;
             Thoracic Society (ATS) / European Respiratory Society (ERS);&#xD;
&#xD;
          -  smokers or former smokers with a smoking history of at least 10 pack / years;&#xD;
&#xD;
          -  subjects with a post-bronchodilator forced expiratory volume at the 1st second (FEV1)/&#xD;
             forced vital capacity (FVC) ratio of &lt; 0.7 and a FEV1 &lt;50% pred;&#xD;
&#xD;
          -  subjects with a high impact of the COPD on their health status (CAT≥10);&#xD;
&#xD;
          -  clinical history of at least 1 moderate exacerbation / year;&#xD;
&#xD;
          -  COPD patients being treated with BDP/FF NEXThaler® 100/6 μg in extra-fine formulation&#xD;
             no more than 1 (one) week before enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  an exacerbation in the four weeks prior to enrollment;&#xD;
&#xD;
          -  other coexisting lung diseases (bronchial asthma, restrictive diseases or&#xD;
             bronchiectasis) and severe co-morbidities associated with COPD, such as uncontrolled&#xD;
             cardiovascular disease, pneumonia or cancer;&#xD;
&#xD;
          -  pregnant patients;&#xD;
&#xD;
          -  subjects unable to meet the criteria of acceptability and repeatability of pulmonary&#xD;
             function tests, according to the ATS / ERS document&#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>Alfredo A Chetta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital-University of Parma, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Italy</name>
      <address>
        <city>Parma</city>
        <zip>43125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>http://goldcopd.org.</url>
    <description>Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018</description>
  </link>
  <link>
    <url>http://www.catestonline.org</url>
    <description>CAT Development Steering Group: COPD Assessment Test - Healthcare Professional User Guide. Issue 4: November 2018.</description>
  </link>
  <results_reference>
    <citation>Burgel PR. The role of small airways in obstructive airway diseases. Eur Respir Rev. 2011 Mar;20(119):23-33. doi: 10.1183/09059180.00010410. Erratum In: Eur Respir Rev. 2011 Jun;20(120):123. Dosage error in article text. Eur Respir Rev. 2011 Jun;20(120):124.</citation>
    <PMID>21357889</PMID>
  </results_reference>
  <results_reference>
    <citation>Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004 Jun 24;350(26):2645-53. doi: 10.1056/NEJMoa032158.</citation>
    <PMID>15215480</PMID>
  </results_reference>
  <results_reference>
    <citation>Crisafulli E, Pisi R, Aiello M, Vigna M, Tzani P, Torres A, Bertorelli G, Chetta A. Prevalence of Small-Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the Impact of Disease. Respiration. 2017;93(1):32-41. doi: 10.1159/000452479. Epub 2016 Nov 17.</citation>
    <PMID>27852080</PMID>
  </results_reference>
  <results_reference>
    <citation>Wedzicha JA, Singh D, Vestbo J, Paggiaro PL, Jones PW, Bonnet-Gonod F, Cohuet G, Corradi M, Vezzoli S, Petruzzelli S, Agusti A; FORWARD Investigators. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014 Aug;108(8):1153-62. doi: 10.1016/j.rmed.2014.05.013. Epub 2014 Jun 6. Erratum In: Respir Med. 2015 Mar;109(3):434-5.</citation>
    <PMID>24953015</PMID>
  </results_reference>
  <results_reference>
    <citation>Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994 Nov;47(11):1245-51. doi: 10.1016/0895-4356(94)90129-5.</citation>
    <PMID>7722560</PMID>
  </results_reference>
  <results_reference>
    <citation>George J, Kong DC, Thoman R, Stewart K. Factors associated with medication nonadherence in patients with COPD. Chest. 2005 Nov;128(5):3198-204. doi: 10.1378/chest.128.5.3198.</citation>
    <PMID>16304262</PMID>
  </results_reference>
  <results_reference>
    <citation>Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5-40. No abstract available.</citation>
    <PMID>8499054</PMID>
  </results_reference>
  <results_reference>
    <citation>Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. doi: 10.1183/09031936.03.00089403.</citation>
    <PMID>14680096</PMID>
  </results_reference>
  <results_reference>
    <citation>Oppenheimer BW, Goldring RM, Herberg ME, Hofer IS, Reyfman PA, Liautaud S, Rom WN, Reibman J, Berger KI. Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure. Chest. 2007 Oct;132(4):1275-82. doi: 10.1378/chest.07-0913. Epub 2007 Sep 21.</citation>
    <PMID>17890470</PMID>
  </results_reference>
  <results_reference>
    <citation>Kon SS, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, Haselden BM, Polkey MI, Man WD. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med. 2014 Mar;2(3):195-203. doi: 10.1016/S2213-2600(14)70001-3. Epub 2014 Feb 4.</citation>
    <PMID>24621681</PMID>
  </results_reference>
  <results_reference>
    <citation>Han MK, Quibrera PM, Carretta EE, Barr RG, Bleecker ER, Bowler RP, Cooper CB, Comellas A, Couper DJ, Curtis JL, Criner G, Dransfield MT, Hansel NN, Hoffman EA, Kanner RE, Krishnan JA, Martinez CH, Pirozzi CB, O'Neal WK, Rennard S, Tashkin DP, Wedzicha JA, Woodruff P, Paine R 3rd, Martinez FJ; SPIROMICS investigators. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017 Aug;5(8):619-626. doi: 10.1016/S2213-2600(17)30207-2. Epub 2017 Jun 28.</citation>
    <PMID>28668356</PMID>
  </results_reference>
  <results_reference>
    <citation>Hogg JC, Chu FS, Tan WC, Sin DD, Patel SA, Pare PD, Martinez FJ, Rogers RM, Make BJ, Criner GJ, Cherniack RM, Sharafkhaneh A, Luketich JD, Coxson HO, Elliott WM, Sciurba FC. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med. 2007 Sep 1;176(5):454-9. doi: 10.1164/rccm.200612-1772OC. Epub 2007 Jun 7.</citation>
    <PMID>17556723</PMID>
  </results_reference>
  <results_reference>
    <citation>Basile M, Baiamonte P, Mazzuca E, Principe S, Pennavaria F, Benfante A, Scichilone N. Sleep Disturbances in COPD are Associated with Heterogeneity of Airway Obstruction. COPD. 2018 Jun-Aug;15(4):350-354. doi: 10.1080/15412555.2018.1504015. Epub 2018 Sep 6.</citation>
    <PMID>30188194</PMID>
  </results_reference>
  <results_reference>
    <citation>De Backer W, Devolder A, Poli G, Acerbi D, Monno R, Herpich C, Sommerer K, Meyer T, Mariotti F. Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):137-48. doi: 10.1089/jamp.2009.0772.</citation>
    <PMID>20109122</PMID>
  </results_reference>
  <results_reference>
    <citation>de Boer AH, Gjaltema D, Hagedoorn P, Frijlink HW. Can 'extrafine' dry powder aerosols improve lung deposition? Eur J Pharm Biopharm. 2015 Oct;96:143-51. doi: 10.1016/j.ejpb.2015.07.016. Epub 2015 Jul 26.</citation>
    <PMID>26220014</PMID>
  </results_reference>
  <results_reference>
    <citation>Virchow JC, Poli G, Herpich C, Kietzig C, Ehlich H, Braeutigam D, Sommerer K, Haussermann S, Mariotti F. Lung Deposition of the Dry Powder Fixed Combination Beclometasone Dipropionate Plus Formoterol Fumarate Using NEXThaler(R) Device in Healthy Subjects, Asthmatic Patients, and COPD Patients. J Aerosol Med Pulm Drug Deliv. 2018 Oct;31(5):269-280. doi: 10.1089/jamp.2016.1359. Epub 2018 Jul 10.</citation>
    <PMID>29989511</PMID>
  </results_reference>
  <results_reference>
    <citation>Voshaar T, Spinola M, Linnane P, Campanini A, Lock D, Lafratta A, Scuri M, Ronca B, Melani AS. Comparing usability of NEXThaler((R)) with other inhaled corticosteroid/long-acting beta2-agonist fixed combination dry powder inhalers in asthma patients. J Aerosol Med Pulm Drug Deliv. 2014 Oct;27(5):363-70. doi: 10.1089/jamp.2013.1086. Epub 2013 Dec 3.</citation>
    <PMID>24299501</PMID>
  </results_reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Parma</investigator_affiliation>
    <investigator_full_name>Alfredo Antonio Chetta</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Beclomethasone</mesh_term>
    <mesh_term>Formoterol Fumarate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All individual participant data collected in this study are available to other researches</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>The data will become available starting from 6 months after publication</ipd_time_frame>
    <ipd_access_criteria>Data will be shared with the Principal Investigator and the authors, if requested, by e-mail contacting</ipd_access_criteria>
    <ipd_url>http://unipr.it</ipd_url>
  </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/NCT04421742
org study id: 9769 del 15.03.2017
nct id: NCT04421742
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In patients with chronic obstructive pulmonary disease (COPD), small-airway dysfunction (SAD)
      is considered a key element and a functional consequence of the pathology. However, the exact
      role of SAD as a specific 'pharmacological target' is not yet fully known.

      Objectives In an open-label prospective study, we aimed to ascertain whether an extra-fine
      formulation of Beclomethasone dipropionate/Formoterol fumarate (BDP/FF) NEXThaler® 100/6 μg
      b.i.d. can improve the impact of the disease on the quality of daily life of COPD patients,
      acting on SAD.

      Methods We studied COPD patients with severe airflow obstruction and 1 moderate exacerbation
      in the previous year, being treated with BDP/FF NEXThaler® for 12 weeks. They underwent three
      visits, at the start of the treatment (V1), at 6th week (V2) and at 12th week (V3). By the
      impulse oscillometry system and by spirometry and plethysmography we measured at each visit
      the fall in resistance from 5 to 20 Hz (R5-R20) and the residual volume/total lung capacity
      (RV/TLC). COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC)
      questionnaire were also measured at each visit to assess the impact of the disease on the
      quality of life of the patients.
In recent years, there has been a growing interest in deepening the contribution of small
      airways (with a diameter <2mm) to the clinical expression of Chronic Obstructive Pulmonary
      Disease (COPD).

      In patients with stable COPD, SAD severity was found to be progressively increased both with
      the degree of airflow obstruction and with GOLD risk class. Moreover, a correlation between
      SAD and COPD impact measured with the CAT (COPD Assessment Test) was found, being the
      severity of SAD a predictor of the impact of the disease (CAT≥10). A close correlation
      between SAD and both quality of life (measured with the St. George's Respiratory
      Questionnaire) and perceived dyspnea (measured with the modified Medical Research
      Council-mMRC scale) was also found in COPD patients.

      The exact role of SAD as a specific 'pharmacological target' is not yet fully known.
      According to the guidelines, the administration of combination such as Beclomethasone
      dipropionate/Formoterol fumarate (BDP/FF) in extra-fine formulation produced a clinically
      relevant improvement in quality of life (> 4 units in the St. George's Respiratory
      Questionnaire) and in dyspnea. However, it is not yet defined whether exists a correlation
      between symptomatic improvement and SAD and whether an improvement of symptoms can be
      achieved acting pharmacologically on SAD.

      The rationale for this study is based on the hypothesis that an extra-fine formulation of
      BDP/FF, designed to target the entire bronchial three, included the peripheral zone, can
      improve the impact of the disease on the quality of life of COPD patients, acting on SAD. The
      functional indices of SAD used in this study are from the impulse oscillometry system (IOS),
      the standard spirometry and the body plethysmography.

      The primary endpoint of the study was, therefore, an improvement of the impact of the disease
      on quality of daily life (CAT) and of dyspnea (mMRC) after 12th week treatment with an
      extra-fine formulation of BDP/FF in a cohort of COPD patients with severe airway obstruction
      and one moderate exacerbation in a previous year; secondary endpoint was an improvement of
      the SAD at the 12th week in these patients.
observational model: Cohort
time perspective: Prospective
measure: Change (Improvement) of CAT (Italian version)
time frame: Change from Baseline CAT at 12th week
description: The CAT (COPD Assessment Test) is a questionnaire suitable for completion by all patients diagnosed with COPD. It comprises 8 simple questions that most patients should be able to understand and complete independently.
The CAT has a scoring range of 0-40, where each question is ranging 0-5. A CAT score>10 indicates a medium/high impact level of COPD.
A difference or change of 2 or more units over 2 to 3 months in a patient suggests a clinically significant difference or change in health status (minimal clinically relevant change, often referred to as the Minimum Clinically Important Difference or MCID).
measure: Change (Improvement) of mMRC (Italian version)
time frame: Change from Baseline mMRC at 12th week
description: The modified Medical Research Council (mMRC) dyspnoea scale is a questionnaire that consists of five statements about perceived breathlessness: grade 1, "I only get breathless with strenuous exercise"; grade 2, "I get short of breath when hurrying on the level or up a slight hill"; grade 3, "I walk slower than people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level"; grade 4, "I stop for breath after walking 100 yards or after a few minutes on the level"; grade 5, " I am too breathless to leave the house". Patients are asked about their perceived breathlessness and are then classified into MRC dyspnoea grades according to how they perceive their disability.
measure: Change (Improvement) of R5-R20 (kPa x s x L-1)
time frame: Change from Baseline R5-R20 at 12th week
description: The IOS was performed with the Jaeger MasterScreen-IOS device following the standard recommendations. Respiratory resistances at 5 Hz and 20 Hz (R5 and R20, kPa x s x L-1) were used as a total and proximal airway resistance index, respectively, and the resistance drop from 5 to 20 Hz (R5 - R20, kPa x s x L-1) was considered as an indirect index of resistance of the peripheral airways. The oscillometer was calibrated daily.
arm group label: 43 COPD
description: COPD patients with severe airflow obstruction and 1 moderate exacerbation in the previous year being treated with BDP/FF NEXThaler® 100/6 μg b.i.d. for 12 weeks
intervention type: Drug
intervention name: Beclomethasone Dipropionate/Formoterol Fumarate
description: BDP/FF NEXThaler® 100/6 μg b.i.d.
arm group label: 43 COPD
other name: Foster NEXThaler®
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Alfredo A Chetta, MD
role: Principal Investigator
affiliation: Hospital-University of Parma, Italy
facility: 
country: Italy
url: http://goldcopd.org.
description: Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018
url: http://www.catestonline.org
description: CAT Development Steering Group: COPD Assessment Test - Healthcare Professional User Guide. Issue 4: November 2018.
citation: Burgel PR. The role of small airways in obstructive airway diseases. Eur Respir Rev. 2011 Mar;20(119):23-33. doi: 10.1183/09059180.00010410. Erratum In: Eur Respir Rev. 2011 Jun;20(120):123. Dosage error in article text. Eur Respir Rev. 2011 Jun;20(120):124.
PMID: 21357889
citation: Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Pare PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004 Jun 24;350(26):2645-53. doi: 10.1056/NEJMoa032158.
PMID: 15215480
citation: Crisafulli E, Pisi R, Aiello M, Vigna M, Tzani P, Torres A, Bertorelli G, Chetta A. Prevalence of Small-Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the Impact of Disease. Respiration. 2017;93(1):32-41. doi: 10.1159/000452479. Epub 2016 Nov 17.
PMID: 27852080
citation: Wedzicha JA, Singh D, Vestbo J, Paggiaro PL, Jones PW, Bonnet-Gonod F, Cohuet G, Corradi M, Vezzoli S, Petruzzelli S, Agusti A; FORWARD Investigators. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014 Aug;108(8):1153-62. doi: 10.1016/j.rmed.2014.05.013. Epub 2014 Jun 6. Erratum In: Respir Med. 2015 Mar;109(3):434-5.
PMID: 24953015
citation: Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994 Nov;47(11):1245-51. doi: 10.1016/0895-4356(94)90129-5.
PMID: 7722560
citation: George J, Kong DC, Thoman R, Stewart K. Factors associated with medication nonadherence in patients with COPD. Chest. 2005 Nov;128(5):3198-204. doi: 10.1378/chest.128.5.3198.
PMID: 16304262
citation: Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5-40. No abstract available.
PMID: 8499054
citation: Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. doi: 10.1183/09031936.03.00089403.
PMID: 14680096
citation: Oppenheimer BW, Goldring RM, Herberg ME, Hofer IS, Reyfman PA, Liautaud S, Rom WN, Reibman J, Berger KI. Distal airway function in symptomatic subjects with normal spirometry following World Trade Center dust exposure. Chest. 2007 Oct;132(4):1275-82. doi: 10.1378/chest.07-0913. Epub 2007 Sep 21.
PMID: 17890470
citation: Kon SS, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, Haselden BM, Polkey MI, Man WD. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med. 2014 Mar;2(3):195-203. doi: 10.1016/S2213-2600(14)70001-3. Epub 2014 Feb 4.
PMID: 24621681
citation: Han MK, Quibrera PM, Carretta EE, Barr RG, Bleecker ER, Bowler RP, Cooper CB, Comellas A, Couper DJ, Curtis JL, Criner G, Dransfield MT, Hansel NN, Hoffman EA, Kanner RE, Krishnan JA, Martinez CH, Pirozzi CB, O'Neal WK, Rennard S, Tashkin DP, Wedzicha JA, Woodruff P, Paine R 3rd, Martinez FJ; SPIROMICS investigators. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017 Aug;5(8):619-626. doi: 10.1016/S2213-2600(17)30207-2. Epub 2017 Jun 28.
PMID: 28668356
citation: Hogg JC, Chu FS, Tan WC, Sin DD, Patel SA, Pare PD, Martinez FJ, Rogers RM, Make BJ, Criner GJ, Cherniack RM, Sharafkhaneh A, Luketich JD, Coxson HO, Elliott WM, Sciurba FC. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med. 2007 Sep 1;176(5):454-9. doi: 10.1164/rccm.200612-1772OC. Epub 2007 Jun 7.
PMID: 17556723
citation: Basile M, Baiamonte P, Mazzuca E, Principe S, Pennavaria F, Benfante A, Scichilone N. Sleep Disturbances in COPD are Associated with Heterogeneity of Airway Obstruction. COPD. 2018 Jun-Aug;15(4):350-354. doi: 10.1080/15412555.2018.1504015. Epub 2018 Sep 6.
PMID: 30188194
citation: De Backer W, Devolder A, Poli G, Acerbi D, Monno R, Herpich C, Sommerer K, Meyer T, Mariotti F. Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):137-48. doi: 10.1089/jamp.2009.0772.
PMID: 20109122
citation: de Boer AH, Gjaltema D, Hagedoorn P, Frijlink HW. Can 'extrafine' dry powder aerosols improve lung deposition? Eur J Pharm Biopharm. 2015 Oct;96:143-51. doi: 10.1016/j.ejpb.2015.07.016. Epub 2015 Jul 26.
PMID: 26220014
citation: Virchow JC, Poli G, Herpich C, Kietzig C, Ehlich H, Braeutigam D, Sommerer K, Haussermann S, Mariotti F. Lung Deposition of the Dry Powder Fixed Combination Beclometasone Dipropionate Plus Formoterol Fumarate Using NEXThaler(R) Device in Healthy Subjects, Asthmatic Patients, and COPD Patients. J Aerosol Med Pulm Drug Deliv. 2018 Oct;31(5):269-280. doi: 10.1089/jamp.2016.1359. Epub 2018 Jul 10.
PMID: 29989511
citation: Voshaar T, Spinola M, Linnane P, Campanini A, Lock D, Lafratta A, Scuri M, Ronca B, Melani AS. Comparing usability of NEXThaler((R)) with other inhaled corticosteroid/long-acting beta2-agonist fixed combination dry powder inhalers in asthma patients. J Aerosol Med Pulm Drug Deliv. 2014 Oct;27(5):363-70. doi: 10.1089/jamp.2013.1086. Epub 2013 Dec 3.
PMID: 24299501
responsible party type: Sponsor-Investigator
investigator affiliation: University of Parma
investigator full name: Alfredo Antonio Chetta
investigator title: Clinical Professor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Beclomethasone
mesh term: Formoterol Fumarate
sharing ipd: Yes
ipd description: All individual participant data collected in this study are available to other researches
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: The data will become available starting from 6 months after publication
ipd access criteria: Data will be shared with the Principal Investigator and the authors, if requested, by e-mail contacting
ipd url: http://unipr.it