<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/NCT03265145</url>
  </required_header>
  <id_info>
    <org_study_id>1237-0064</org_study_id>
    <nct_id>NCT03265145</nct_id>
  </id_info>
  <brief_title>Assessment In a Real World Setting of the Effect of Inhaled Steroid-based Triple Therapy Versus the Combination of Tiotropium and Olodaterol on Reducing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations [AIRWISE]</brief_title>
  <official_title>Randomized Pragmatic Clinical Trial in a Community-Based Setting Comparing STIOLTO® RESPIMAT® vs. ICS-LABA Plus LAMA in Patients With COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Carelon Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this pragmatic study is to compare the time to first moderate or&#xD;
      severe COPD exacerbation in patients, not controlled on their current therapy, randomized to&#xD;
      Stiolto Respimat versus triple therapy over 12 months of treatment&#xD;
&#xD;
      The secondary objectives of this study include:&#xD;
&#xD;
        1. To compare the annual rate of moderate or severe COPD exacerbations for patients on&#xD;
           Stiolto Respimat with patients on triple therapy.&#xD;
&#xD;
        2. To compare the time to first severe COPD exacerbation in both treatment arms.&#xD;
&#xD;
        3. To compare the annual rate of severe COPD exacerbations in both treatment arms.&#xD;
&#xD;
        4. To compare the proportion of patients with moderate or severe COPD exacerbations in both&#xD;
           treatment arms.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 20, 2017</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the 12 Month Study Period</measure>
    <time_frame>Baseline till end of study, up to 12 months.</time_frame>
    <description>Time to first moderate or severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annual Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations</measure>
    <time_frame>Baseline till end of study, up to 12 months.</time_frame>
    <description>Annual rate of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over 12 Months of Treatment Pulmonary Disease</measure>
    <time_frame>Baseline till end of study, up to 12 months.</time_frame>
    <description>Time to first severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annual Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations</measure>
    <time_frame>Baseline till end of study, up to 12 months.</time_frame>
    <description>Annual rate of severe chronic obstructive pulmonary disease (COPD) exacerbations.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 12 Month Observation Period</measure>
    <time_frame>12 months after baseline.</time_frame>
    <description>Number of patients with moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations over the 12 month observation period.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">714</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Stiolto Respimat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ICS plus LABA plus LAMA (triple therapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ICS (Inhaled Corticosteroid) plus LABA (Long-Acting Beta Agonist) plus (Long-Acting Muscarinic Antagonist)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stiolto Respimat</intervention_name>
    <description>Duration - 12 months</description>
    <arm_group_label>Stiolto Respimat</arm_group_label>
    <other_name>INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ICS (Inhaled Corticosteroid) (Triple therapy)</intervention_name>
    <description>Duration - 12 months</description>
    <arm_group_label>ICS plus LABA plus LAMA (triple therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LABA (Long-Acting Beta Agonist) (Triple therapy)</intervention_name>
    <description>Duration - 12 months</description>
    <arm_group_label>ICS plus LABA plus LAMA (triple therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LAMA (Long-Acting Muscarinic Antagonist) (Triple therapy)</intervention_name>
    <description>Duration - 12 months</description>
    <arm_group_label>ICS plus LABA plus LAMA (triple therapy)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD diagnosis as defined by the study physician&#xD;
&#xD;
          -  Currently on one of the following maintenance therapies:&#xD;
&#xD;
               -  LAMA monotherapy&#xD;
&#xD;
               -  LABA monotherapy&#xD;
&#xD;
               -  ICS/LABA (FDC)&#xD;
&#xD;
          -  Physician determination that patient is not controlled on current pharmacotherapy&#xD;
&#xD;
          -  Adult patient 40 years of age or older at time of study enrollment&#xD;
&#xD;
          -  Willingness and ability to understand and provide documented Informed Consent Form&#xD;
             (ICF) and Health Insurance Portability and Accountability Act (HIPAA) Authorization&#xD;
             Form prior to commencement of any study required assessments, either directly or&#xD;
             through Legally Authorized Representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently on LAMA/LABA (free or FDC) or triple therapy (ICS plus LABA plus LAMA)&#xD;
&#xD;
          -  Contraindication to any study medications (LAMA, LABA or ICS)&#xD;
&#xD;
          -  Documented diagnosis of current asthma&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Women of childbearing potential are not restricted in this trial, however it is&#xD;
             expected that the investigator will assess the risks and benefits of the assigned&#xD;
             treatment as per the product label(s) and discuss this with any women of childbearing&#xD;
             potential prior to providing the patient with the prescription for the assigned&#xD;
             treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pulmonary Associates of Mobile, PC</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthscan Clinical Trials LLC</name>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <zip>36106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthScan Research</name>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <zip>36109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diamond Childrens Medical Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CareMore Apple Valley Care Center</name>
      <address>
        <city>Apple Valley</city>
        <state>California</state>
        <zip>92308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HealthCare Partners</name>
      <address>
        <city>Commerce</city>
        <state>California</state>
        <zip>90040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Research Center, Inc.</name>
      <address>
        <city>Murrieta</city>
        <state>California</state>
        <zip>92562</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newport Native MD, Inc</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aureus Medical Group, Inc</name>
      <address>
        <city>Rancho Cucamonga</city>
        <state>California</state>
        <zip>91730</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Allergy and Respiratory Disease Center</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Paloma Medical Group</name>
      <address>
        <city>San Juan Capistrano</city>
        <state>California</state>
        <zip>92675</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adnab Research/Prestige Care Physician</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary and Sleep of Tampa Bay</name>
      <address>
        <city>Brandon</city>
        <state>Florida</state>
        <zip>33511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Research of West Florida, Inc.</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Sleep, Allergy and Lung Institute, LLC</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cohen Medical Research Associates, LLC</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33446</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gary J. Richmond, M.D., PA</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research of Central Florida</name>
      <address>
        <city>Leesburg</city>
        <state>Florida</state>
        <zip>34748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Lung and Sleep Associates</name>
      <address>
        <city>Lehigh Acres</city>
        <state>Florida</state>
        <zip>33971</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TRY Research</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pro Live Medical Research</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Research for Health Improvement, LLC</name>
      <address>
        <city>Naples</city>
        <state>Florida</state>
        <zip>34102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oviedo Medical Research</name>
      <address>
        <city>Oviedo</city>
        <state>Florida</state>
        <zip>32765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pasadena Ctr for Medical Rsrch</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33707</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bassetti Medical Research Inc</name>
      <address>
        <city>Sebring</city>
        <state>Florida</state>
        <zip>33870</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Suen MD PA</name>
      <address>
        <city>Vero Beach</city>
        <state>Florida</state>
        <zip>32960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gwinnett Research Institute</name>
      <address>
        <city>Buford</city>
        <state>Georgia</state>
        <zip>30519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary and Sleep Specialists, PC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DC Pulmonary Medicine</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern IL Clinical Rsrch Ctr</name>
      <address>
        <city>O'Fallon</city>
        <state>Illinois</state>
        <zip>62269</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Network of Indiana, LLC</name>
      <address>
        <city>Franklin</city>
        <state>Indiana</state>
        <zip>46131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Network of Indiana, LLC</name>
      <address>
        <city>Greenfield</city>
        <state>Indiana</state>
        <zip>46140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The LaPorte County Institute for Clinical Research</name>
      <address>
        <city>Michigan City</city>
        <state>Indiana</state>
        <zip>46360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ball Memorial Hospital</name>
      <address>
        <city>Muncie</city>
        <state>Indiana</state>
        <zip>47303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Network</name>
      <address>
        <city>New Albany</city>
        <state>Indiana</state>
        <zip>47150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kentucky Lung Clinic</name>
      <address>
        <city>Georgetown</city>
        <state>Kentucky</state>
        <zip>40324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary and Sleep Clinic PLLV</name>
      <address>
        <city>Hopkinsville</city>
        <state>Kentucky</state>
        <zip>42240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary and Critical Care Associates of Baltimore</name>
      <address>
        <city>Bel Air</city>
        <state>Maryland</state>
        <zip>21014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary and Critical Care Associates of Baltimore</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21286</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lahey Hospital and Medical Center</name>
      <address>
        <city>Burlington</city>
        <state>Massachusetts</state>
        <zip>01805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vida Clinical Studies</name>
      <address>
        <city>Dearborn</city>
        <state>Michigan</state>
        <zip>48124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Flint Clinical Research</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clayton Sleep Institute</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Surgery Center</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jubilee Clinical Research, Inc</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shore Pulmonary, PA</name>
      <address>
        <city>Ocean City</city>
        <state>New Jersey</state>
        <zip>07712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bassett Medical Center</name>
      <address>
        <city>Cooperstown</city>
        <state>New York</state>
        <zip>13326</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Health Physicians</name>
      <address>
        <city>Fayetteville</city>
        <state>New York</state>
        <zip>13066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Feinstein Institute for Medical Research</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lenox Hill Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orchard Park Family Practice</name>
      <address>
        <city>Orchard Park</city>
        <state>New York</state>
        <zip>14127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Research, Inc.</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of Gastonia</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Carolina Health Care, P.A.</name>
      <address>
        <city>New Bern</city>
        <state>North Carolina</state>
        <zip>28562</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tabor City Family Medicine</name>
      <address>
        <city>Tabor City</city>
        <state>North Carolina</state>
        <zip>28463</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goshen Medical Center</name>
      <address>
        <city>Whiteville</city>
        <state>North Carolina</state>
        <zip>28472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Research Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Catherine LaRuffa, MD, Inc.</name>
      <address>
        <city>Blanchester</city>
        <state>Ohio</state>
        <zip>45107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Medical Primary Care</name>
      <address>
        <city>Centerville</city>
        <state>Ohio</state>
        <zip>45459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Cleveland</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Pulmonary and Sleep Research</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio Sleep and Pulmonary Center</name>
      <address>
        <city>Englewood</city>
        <state>Ohio</state>
        <zip>45322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prestige Clinical Research</name>
      <address>
        <city>Franklin</city>
        <state>Ohio</state>
        <zip>45005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert Santiago MD, Inc.</name>
      <address>
        <city>Galion</city>
        <state>Ohio</state>
        <zip>44833</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary, Critical Care and Sleep Medicine Associates</name>
      <address>
        <city>Hamilton</city>
        <state>Ohio</state>
        <zip>45013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wells Inst for Hlth Awareness</name>
      <address>
        <city>Kettering</city>
        <state>Ohio</state>
        <zip>45429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Medicine</name>
      <address>
        <city>South Euclid</city>
        <state>Ohio</state>
        <zip>44121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toledo Clinic Incorporated</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43623</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio Clinical Research, LLC</name>
      <address>
        <city>Willoughby Hills</city>
        <state>Ohio</state>
        <zip>44094</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Internal Medicine, Inc.</name>
      <address>
        <city>Wooster</city>
        <state>Ohio</state>
        <zip>44691</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Preferred Primary Care Phys</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Preferred Primary Care Phys</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frontier Clinical Research, LLC</name>
      <address>
        <city>Scottdale</city>
        <state>Pennsylvania</state>
        <zip>15683</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Frontier Clinical Research LLC</name>
      <address>
        <city>Smithfield</city>
        <state>Pennsylvania</state>
        <zip>15478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Preferred Primary Care Phys</name>
      <address>
        <city>Uniontown</city>
        <state>Pennsylvania</state>
        <zip>15401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Medical Research</name>
      <address>
        <city>Clinton</city>
        <state>South Carolina</state>
        <zip>29325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Main Street Physicians Care</name>
      <address>
        <city>Little River</city>
        <state>South Carolina</state>
        <zip>29566</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Family Medicine of SayeBrook</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29588</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Pulmonary Sleep Allergy and Asthma Associates</name>
      <address>
        <city>Cypress</city>
        <state>Texas</state>
        <zip>77429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Health Physicians Group</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Texas Lung &amp; Sleep Clnc</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SMS Clinical Research</name>
      <address>
        <city>Mesquite</city>
        <state>Texas</state>
        <zip>75149</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Marcos Family Medicine</name>
      <address>
        <city>San Marcos</city>
        <state>Texas</state>
        <zip>78666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texarkana Clinical Research</name>
      <address>
        <city>Texarkana</city>
        <state>Texas</state>
        <zip>75503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chesapeake Pulmonary and Critical Care</name>
      <address>
        <city>Chesapeake</city>
        <state>Virginia</state>
        <zip>23320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richmond Family Practice</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare Institute</name>
      <address>
        <city>Cheney</city>
        <state>Washington</state>
        <zip>99004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Washington Medical Grp</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary and Critical Care Associates, SC</name>
      <address>
        <city>Cudahy</city>
        <state>Wisconsin</state>
        <zip>53110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <results_first_submitted>September 29, 2021</results_first_submitted>
  <results_first_submitted_qc>December 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 9, 2021</results_first_posted>
  <last_update_submitted>May 24, 2022</last_update_submitted>
  <last_update_submitted_qc>May 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</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>Cholinergic Agents</mesh_term>
    <mesh_term>Muscarinic Antagonists</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Once the criteria in section &quot;Time Frame&quot; are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed &quot;Document Sharing Agreement&quot;.&#xD;
Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.</ipd_access_criteria>
    <ipd_url>https://www.mystudywindow.com/msw/datasharing</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 9, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT03265145/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT03265145/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a pragmatic randomized open label active controlled parallel group design trial conducted in a real-world, community-based practice setting. Participants were on long-acting muscarinic antagonist (LAMA), long-acting beta agonist (LABA) or Inhaled Corticosteroid (ICS)/LABA for COPD, but were determined by their physician to not be controlled on their current therapy. Subjects were randomized to either Stiolto Respimat or ICS plus LABA plus LAMA (triple therapy) for the study.</recruitment_details>
      <pre_assignment_details>All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Stiolto® Respimat®</title>
          <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
        </group>
        <group group_id="P2">
          <title>ICS Plus LABA Plus LAMA (Triple Therapy)</title>
          <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="356"/>
                <participants group_id="P2" count="358"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="285"/>
                <participants group_id="P2" count="302"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>missing end of study form, could not definitely count as completion or discontinuation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Switched back to previous medication</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not want to take medication</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject could not afford medication</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Site closed</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Incorrectly randomized</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Entered into Electronic Data Capture in error</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject transferred to another facility</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Stiolto® Respimat®</title>
          <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
        </group>
        <group group_id="B2">
          <title>ICS Plus LABA Plus LAMA (Triple Therapy)</title>
          <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="356"/>
            <count group_id="B2" value="358"/>
            <count group_id="B3" value="714"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.0" spread="9.32"/>
                    <measurement group_id="B2" value="69.9" spread="9.81"/>
                    <measurement group_id="B3" value="69.5" spread="9.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="181"/>
                    <measurement group_id="B2" value="174"/>
                    <measurement group_id="B3" value="355"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="169"/>
                    <measurement group_id="B2" value="181"/>
                    <measurement group_id="B3" value="350"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="329"/>
                    <measurement group_id="B2" value="334"/>
                    <measurement group_id="B3" value="663"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White or Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="292"/>
                    <measurement group_id="B2" value="300"/>
                    <measurement group_id="B3" value="592"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the 12 Month Study Period</title>
        <description>Time to first moderate or severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.</description>
        <time_frame>Baseline till end of study, up to 12 months.</time_frame>
        <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Stiolto® Respimat®</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
          <group group_id="O2">
            <title>ICS Plus LABA Plus LAMA (Triple Therapy)</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the 12 Month Study Period</title>
          <description>Time to first moderate or severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.</description>
          <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="348"/>
                <count group_id="O2" value="354"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Non-calculable as the median was not reached (and neither was the Q1).</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Non-calculable as the median was not reached (and neither was the Q1).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.87</ci_lower_limit>
            <ci_upper_limit>1.72</ci_upper_limit>
            <estimate_desc>Cox proportional hazards model with baseline ICS prior use as a covariate was used to estimate the hazard ratio (HR) and the two-sided 95% Wald confidence interval (CI).&#xD;
Ratio: Stiolto Respimat/triple therapy.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations</title>
        <description>Annual rate of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.</description>
        <time_frame>Baseline till end of study, up to 12 months.</time_frame>
        <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Stiolto® Respimat®</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
          <group group_id="O2">
            <title>Triple Therapy</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients were switched to a treatment of ICS plus LABA plus LAMA (triple therapy), made up of the combination of any approved drugs that their physician chooses, for 12 months of treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations</title>
          <description>Annual rate of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.</description>
          <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
          <units>Exacerbations per participant per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="348"/>
                <count group_id="O2" value="354"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.36" lower_limit="0.28" upper_limit="0.47"/>
                    <measurement group_id="O2" value="0.26" lower_limit="0.19" upper_limit="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>adjusted annual rate ratio</param_type>
            <param_value>1.41</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.97</ci_lower_limit>
            <ci_upper_limit>2.04</ci_upper_limit>
            <estimate_desc>Ratio: Stiolto Respimat/triple therapy</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over 12 Months of Treatment Pulmonary Disease</title>
        <description>Time to first severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.</description>
        <time_frame>Baseline till end of study, up to 12 months.</time_frame>
        <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Stiolto® Respimat®</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
          <group group_id="O2">
            <title>ICS Plus LABA Plus LAMA (Triple Therapy)</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over 12 Months of Treatment Pulmonary Disease</title>
          <description>Time to first severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.</description>
          <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="348"/>
                <count group_id="O2" value="354"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Non-calculable as the median was not reached (and neither was the Q1).</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Non-calculable as the median was not reached (and neither was the Q1).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.11</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>2.00</ci_upper_limit>
            <estimate_desc>Cox proportional hazards model with baseline ICS prior use as a covariate was used to estimate the hazard ratio (HR) and the two-sided 95% Wald confidence interval (CI).&#xD;
Ratio: Stiolto Respimat/triple therapy.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations</title>
        <description>Annual rate of severe chronic obstructive pulmonary disease (COPD) exacerbations.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.</description>
        <time_frame>Baseline till end of study, up to 12 months.</time_frame>
        <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Stiolto® Respimat®</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
          <group group_id="O2">
            <title>Triple Therapy</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients were switched to a treatment of ICS plus LABA plus LAMA (triple therapy), made up of the combination of any approved drugs that their physician chooses, for 12 months of treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations</title>
          <description>Annual rate of severe chronic obstructive pulmonary disease (COPD) exacerbations.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).&#xD;
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.</description>
          <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
          <units>Exacerbations per participant per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="348"/>
                <count group_id="O2" value="354"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07" lower_limit="0.04" upper_limit="0.12"/>
                    <measurement group_id="O2" value="0.07" lower_limit="0.04" upper_limit="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>adjusted annual rate ratio</param_type>
            <param_value>1.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.58</ci_lower_limit>
            <ci_upper_limit>2.01</ci_upper_limit>
            <estimate_desc>Ratio: Stiolto Respimat/triple therapy</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 12 Month Observation Period</title>
        <description>Number of patients with moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations over the 12 month observation period.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).</description>
        <time_frame>12 months after baseline.</time_frame>
        <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Stiolto® Respimat®</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
          </group>
          <group group_id="O2">
            <title>Triple Therapy</title>
            <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients were switched to a treatment of ICS plus LABA plus LAMA (triple therapy), made up of the combination of any approved drugs that their physician chooses, for 12 months of treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 12 Month Observation Period</title>
          <description>Number of patients with moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations over the 12 month observation period.&#xD;
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.&#xD;
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).</description>
          <population>Intent to Treat (ITT) Population: The ITT population will include all randomized patients allocated to their original randomized treatment group, even if they switched or discontinued study treatment. Only patients with non missing ICS baseline values were included. Due to investigator error, 5 patients in each group received the prescription for the wrong treatment. These subjects were included in the actual treatment, not the randomized treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="348"/>
                <count group_id="O2" value="354"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A Cochran-Mantel-Haenszel (CMH) model with baseline ICS prior use as stratum was used to estimate the Risk Ratio (RR) (Stiolto Respimat versus triple therapy) of moderate or severe COPD exacerbations along with 95% CI.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Risk Ratio (RR)</param_type>
            <param_value>1.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.89</ci_lower_limit>
            <ci_upper_limit>1.64</ci_upper_limit>
            <estimate_desc>Ratio: Stiolto Respimat/triple therapy</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A Cochran-Mantel-Haenszel (CMH) model with baseline ICS prior use as stratum was used to estimate the Risk Difference (Stiolto Respimat versus triple therapy) of moderate or severe COPD exacerbations along with 95% CI.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>0.036</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.022</ci_lower_limit>
            <ci_upper_limit>0.094</ci_upper_limit>
            <estimate_desc>Ratio: Stiolto Respimat/triple therapy</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 12 months + 21 days.</time_frame>
      <desc>All-Cause Mortality: all randomized patients allocated to original randomized treatment group. 5 patients in each group received the wrong prescription, these were included in the actual treatment.&#xD;
Adverse events (AE): all randomized patients who received a prescription of any study treatment.&#xD;
Non-serious AE collection and reporting was limited to events leading to trial discontinuation, treatment discontinuation or death as this is an approved product with a known safety profile.</desc>
      <group_list>
        <group group_id="E1">
          <title>Stiolto® Respimat®</title>
          <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following Stiolto® Respimat® treatment: Fixed dose of 2.5 micrograms (mcg) tiotropium and 2.5 mcg olodaterol (Stiolto® Respimat®) per actuation were inhaled twice daily (tiotropium/olodaterol daily dosage: 5/5 mcg). Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
        </group>
        <group group_id="E2">
          <title>ICS Plus LABA Plus LAMA (Triple Therapy)</title>
          <description>Patients with chronic obstructive pulmonary disease (COPD) who were on long-acting muscarinic antagonist (LAMA) or long-acting beta agonist (LABA) or inhaled corticosteroid (ICS)/LABA maintenance therapy, and whose treatment was not controlled on the medication regimen as determined by the physician.&#xD;
Patients started the following ICS plus LABA plus LAMA (triple therapy) treatment made up of the combination of any approved drugs that their physician chooses.Triple Therapy (ICS + LABA + LAMA) was inhaled with dose as prescribed by physicians per label for selected medications. Patients were followed for 12 months regardless of treatment switching or discontinuing study treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="356"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="358"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Acute left ventricular failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Atrioventricular block second degree</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cardiac failure chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Left ventricular failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Generalised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Bronchitis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Escherichia sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of chronic obstructive airways disease</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Parainfluenzae virus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pneumonia mycoplasmal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Urinary tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood osmolarity decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Heart rate increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Bladder cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Chronic lymphocytic leukaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Lung carcinoma cell type unspecified stage III</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Plasma cell myeloma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Small cell lung cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of lung</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carotid artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Polyneuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Toxic encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>End stage renal disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Renal disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Ureteric obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Orthopnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Transcatheter aortic valve implantation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Arteriosclerosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Essential hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
              <event>
                <sub_title>Peripheral vascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="325"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="318"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim, Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03265145
org study id: 1237-0064
nct id: NCT03265145
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this pragmatic study is to compare the time to first moderate or
      severe COPD exacerbation in patients, not controlled on their current therapy, randomized to
      Stiolto Respimat versus triple therapy over 12 months of treatment

      The secondary objectives of this study include:

        1. To compare the annual rate of moderate or severe COPD exacerbations for patients on
           Stiolto Respimat with patients on triple therapy.

        2. To compare the time to first severe COPD exacerbation in both treatment arms.

        3. To compare the annual rate of severe COPD exacerbations in both treatment arms.

        4. To compare the proportion of patients with moderate or severe COPD exacerbations in both
           treatment arms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the 12 Month Study Period
time frame: Baseline till end of study, up to 12 months.
description: Time to first moderate or severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.
measure: Annual Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
time frame: Baseline till end of study, up to 12 months.
description: Annual rate of moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations.
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.
measure: Time to First Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over 12 Months of Treatment Pulmonary Disease
time frame: Baseline till end of study, up to 12 months.
description: Time to first severe chronic obstructive (COPD) exacerbation over 12 months of treatment pulmonary disease.
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).
Median survival time as well as 95% confidence interval was calculated using Kaplan-Meier curves.
measure: Annual Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
time frame: Baseline till end of study, up to 12 months.
description: Annual rate of severe chronic obstructive pulmonary disease (COPD) exacerbations.
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).
Annual rate analysis utilized a negative binomial model with fixed effect of treatment (Stiolto Respimat versus triple therapy), logarithm of observational time as offset, and baseline prior ICS was used as a covariate.
measure: Number of Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Over the 12 Month Observation Period
time frame: 12 months after baseline.
description: Number of patients with moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations over the 12 month observation period.
Moderate exacerbation was a patient receiving an exacerbation-related prescription such as oral corticosteroid (prednisone or prednisolone) and/or antibiotic, but not requiring hospitalization.
Severe exacerbation was a patient requiring hospitalization or emergency room visit due to COPD (ICD-9-491.21 or ICD-10-J44.1).
arm group label: Stiolto Respimat
arm group type: Experimental
arm group label: ICS plus LABA plus LAMA (triple therapy)
arm group type: Active Comparator
description: ICS (Inhaled Corticosteroid) plus LABA (Long-Acting Beta Agonist) plus (Long-Acting Muscarinic Antagonist)
intervention type: Drug
intervention name: Stiolto Respimat
description: Duration - 12 months
arm group label: Stiolto Respimat
other name: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO
intervention type: Drug
intervention name: ICS (Inhaled Corticosteroid) (Triple therapy)
description: Duration - 12 months
arm group label: ICS plus LABA plus LAMA (triple therapy)
intervention type: Drug
intervention name: LABA (Long-Acting Beta Agonist) (Triple therapy)
description: Duration - 12 months
arm group label: ICS plus LABA plus LAMA (triple therapy)
intervention type: Drug
intervention name: LAMA (Long-Acting Muscarinic Antagonist) (Triple therapy)
description: Duration - 12 months
arm group label: ICS plus LABA plus LAMA (triple therapy)
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
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country: United States
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Cholinergic Agents
mesh term: Muscarinic Antagonists
sharing ipd: Yes
ipd description: Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".
Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
ipd access criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
ipd url: https://www.mystudywindow.com/msw/datasharing
provided document: 
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participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 