<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/NCT01693003</url>
  </required_header>
  <id_info>
    <org_study_id>ISCMPALABAtrial</org_study_id>
    <nct_id>NCT01693003</nct_id>
  </id_info>
  <brief_title>Indacaterol Versus Tiotropium on Dynamic Hyperinflation in COPD</brief_title>
  <official_title>Randomized, Open-label, Crossover Clinical Trial to Assess the Effects of Indacaterol 150 µg d.o. Compared to Tiotropium Bromide 5 µg d.o. on Dyspnea, Dynamic Pulmonary Hyperinflation and Exercise Tolerance in Patients With Moderate COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Irmandade Santa Casa de Misericórdia de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Irmandade Santa Casa de Misericórdia de Porto Alegre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Exercise intolerance is a major complain of patients with chronic obstructive pulmonary&#xD;
      disease (COPD). Dynamic hyperinflation has been recognized as an important limiting factor&#xD;
      responsible for the appearance of intolerable dyspnea during exercise. Regular treatment with&#xD;
      long-acting bronchodilators promotes a more sustained reduction of hyperinflation and&#xD;
      consequent symptom relief and increase in the patient's ability to overcome physical demands&#xD;
      of daily life. Tiotropium bromide (TIO) is a new generation, long-acting anticholinergic&#xD;
      bronchodilator that significantly improves lung function, reduces symptoms and improves&#xD;
      exercise tolerance in patients with advanced COPD. Indacaterol is a new ultra-long duration&#xD;
      (&gt;24 h) β2-agonist, which promotes sustained dilation of the bronchi with a once-daily&#xD;
      administration. Compared to tiotropium, indacaterol provides evidence that is as effective as&#xD;
      tiotropium for bronchodilation, as well as other clinical outcomes such as dyspnea and state&#xD;
      of health. However, comparative effects of indacaterol versus tiotropium with regard to&#xD;
      outcomes in tolerance, dyspnea and dynamic lung hyperinflation during exercise is scarce. We&#xD;
      hypothesized that indacaterol and TIO are not different in terms of exercise tolerance and&#xD;
      its determinants (dynamic hyperinflation and dyspnea).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise tolerance</measure>
    <time_frame>3 weeks</time_frame>
    <description>Time between beginning of high intensity constant load (75-85% of the peak achieved in a previous cycloergometer incremental test) cardiopulmonary exercise test and point at which patient cannot tolerate the effort any longer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effort-related dyspnea during daily activities</measure>
    <time_frame>3 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Airway diameter and volume, and extension of pulmonary emphysema by multidetector helical chest computed tomography</measure>
    <time_frame>3 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxidative stress before and after exercise tests</measure>
    <time_frame>3 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exercise dyspnea</measure>
    <time_frame>3 weeks</time_frame>
    <description>Dyspnea evaluated by Borg scale each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dynamic pulmonary hyperinflation</measure>
    <time_frame>3 weeks</time_frame>
    <description>Inspiratory capacity measured each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>Participants will register adverse events in clinical research diaries or communicate to investigator during 3-week treatment period</time_frame>
    <description>Adverse events, including serious adverse events, will be collected and reported in the CRF (Clinical Research File) of the study.&#xD;
Adverse event is any sign, symptom or undesired medical condition that occurs after the beginning of the study even if said event is not considered related to the drug (or therapy) of study. Information on adverse events either reported voluntarily by the patient, identified through questioning by the investigator, or detected by physical examination, laboratory testing or otherwise, will be collected and recorded.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Indacaterol first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Indacaterol 150 µg d.o. during the first 3-week period followed by other 3-week period of tiotropium bromide 5 µg d.o. separated by a &quot;wash-out&quot; phase of at least 5 to 14 days between each treatment period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tiotropium bromide 5 µg d.o. during the first 3-week period followed by other 3-week period of Indacaterol 150 µg d.o. separated by a &quot;wash-out&quot; phase of at least 5 to 14 days between each treatment period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indacaterol</intervention_name>
    <description>150 µg d.o. during the first 3 weeks</description>
    <arm_group_label>Indacaterol first</arm_group_label>
    <arm_group_label>Tiotropium first</arm_group_label>
    <other_name>Onbrez Breezhaler®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>150 µg d.o. during 3 weeks</description>
    <arm_group_label>Indacaterol first</arm_group_label>
    <arm_group_label>Tiotropium first</arm_group_label>
    <other_name>Spiriva Respimat®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women (neither pregnant nor nursing women) ≥40 years of age, with a history of&#xD;
             smoking (&gt;20 years/pack) and COPD diagnosis according to GOLD criteria.&#xD;
&#xD;
          -  Post-bronchodilator FEV1 &gt;50% and &lt;80%, and FEV1/FVC ≤70% of predicted value.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hospital admission due to COPD exacerbation or lung infection in the 6 weeks prior to&#xD;
             screening, diagnosis of current or previous bronchial asthma, history of allergic&#xD;
             rhinitis or other atopic diseases, or peripheral eosinophilia &gt;400/mm3.&#xD;
&#xD;
          -  Inability to discontinue the usual bronchodilator therapy prior to initial screening&#xD;
             tests, need for continuous oxygen therapy, or arterial oxygen saturation &lt;85% at rest,&#xD;
             or history of adverse reactions to sympathomimetic amines or use of inhaled&#xD;
             medication.&#xD;
&#xD;
          -  Anemia, hypo- or hyperthyroidism, hyperadrenergic conditions, uncontrolled&#xD;
             insulin-dependent diabetes mellitus, malignancy, or any disease or condition that&#xD;
             limits exercise capacity other than COPD.&#xD;
&#xD;
          -  History of drug or alcohol abuse, poor adherence to drug treatment, or treatment with&#xD;
             any investigational drug in the month before screening.&#xD;
&#xD;
          -  Patients with ventricular arrhythmia.&#xD;
&#xD;
          -  Patients with &lt;80% oxyhemoglobin saturation during exercise testing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paulo Z Teixeira, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Santa Casa de Misericórdia de Porto Alegre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pavilhão Pereira Filho</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande do Sul</state>
        <zip>90002-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pavilhão Pereira Filho</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>January 6, 2014</last_update_submitted>
  <last_update_submitted_qc>January 6, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Irmandade Santa Casa de Misericórdia de Porto Alegre</investigator_affiliation>
    <investigator_full_name>Paulo J Z Teixeira</investigator_full_name>
    <investigator_title>Clinical professor and chair of the study</investigator_title>
  </responsible_party>
  <keyword>COPD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tiotropium Bromide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01693003
org study id: ISCMPALABAtrial
nct id: NCT01693003
lead sponsor: 
collaborator: 
has dmc: No
Exercise intolerance is a major complain of patients with chronic obstructive pulmonary
      disease (COPD). Dynamic hyperinflation has been recognized as an important limiting factor
      responsible for the appearance of intolerable dyspnea during exercise. Regular treatment with
      long-acting bronchodilators promotes a more sustained reduction of hyperinflation and
      consequent symptom relief and increase in the patient's ability to overcome physical demands
      of daily life. Tiotropium bromide (TIO) is a new generation, long-acting anticholinergic
      bronchodilator that significantly improves lung function, reduces symptoms and improves
      exercise tolerance in patients with advanced COPD. Indacaterol is a new ultra-long duration
      (>24 h) β2-agonist, which promotes sustained dilation of the bronchi with a once-daily
      administration. Compared to tiotropium, indacaterol provides evidence that is as effective as
      tiotropium for bronchodilation, as well as other clinical outcomes such as dyspnea and state
      of health. However, comparative effects of indacaterol versus tiotropium with regard to
      outcomes in tolerance, dyspnea and dynamic lung hyperinflation during exercise is scarce. We
      hypothesized that indacaterol and TIO are not different in terms of exercise tolerance and
      its determinants (dynamic hyperinflation and dyspnea).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Exercise tolerance
time frame: 3 weeks
description: Time between beginning of high intensity constant load (75-85% of the peak achieved in a previous cycloergometer incremental test) cardiopulmonary exercise test and point at which patient cannot tolerate the effort any longer.
measure: Effort-related dyspnea during daily activities
time frame: 3 weeks
measure: Airway diameter and volume, and extension of pulmonary emphysema by multidetector helical chest computed tomography
time frame: 3 weeks
measure: Oxidative stress before and after exercise tests
time frame: 3 weeks
measure: Exercise dyspnea
time frame: 3 weeks
description: Dyspnea evaluated by Borg scale each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise)
measure: Dynamic pulmonary hyperinflation
time frame: 3 weeks
description: Inspiratory capacity measured each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise).
measure: Adverse events
time frame: Participants will register adverse events in clinical research diaries or communicate to investigator during 3-week treatment period
description: Adverse events, including serious adverse events, will be collected and reported in the CRF (Clinical Research File) of the study.
Adverse event is any sign, symptom or undesired medical condition that occurs after the beginning of the study even if said event is not considered related to the drug (or therapy) of study. Information on adverse events either reported voluntarily by the patient, identified through questioning by the investigator, or detected by physical examination, laboratory testing or otherwise, will be collected and recorded.
arm group label: Indacaterol first
arm group type: Experimental
description: Indacaterol 150 µg d.o. during the first 3-week period followed by other 3-week period of tiotropium bromide 5 µg d.o. separated by a "wash-out" phase of at least 5 to 14 days between each treatment period
arm group label: Tiotropium first
arm group type: Experimental
description: Tiotropium bromide 5 µg d.o. during the first 3-week period followed by other 3-week period of Indacaterol 150 µg d.o. separated by a "wash-out" phase of at least 5 to 14 days between each treatment period
intervention type: Drug
intervention name: Indacaterol
description: 150 µg d.o. during the first 3 weeks
arm group label: Indacaterol first
arm group label: Tiotropium first
other name: Onbrez Breezhaler®
intervention type: Drug
intervention name: Tiotropium
description: 150 µg d.o. during 3 weeks
arm group label: Indacaterol first
arm group label: Tiotropium first
other name: Spiriva Respimat®
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Paulo Z Teixeira, MD
role: Study Chair
affiliation: Santa Casa de Misericórdia de Porto Alegre
facility: 
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Irmandade Santa Casa de Misericórdia de Porto Alegre
investigator full name: Paulo J Z Teixeira
investigator title: Clinical professor and chair of the study
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Tiotropium Bromide