<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/NCT02261727</url>
  </required_header>
  <id_info>
    <org_study_id>TGI-Resp-01</org_study_id>
    <secondary_id>1033117</secondary_id>
    <nct_id>NCT02261727</nct_id>
  </id_info>
  <brief_title>Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study</brief_title>
  <acronym>TASCS</acronym>
  <official_title>The Effect of Low-dose Corticosteroids and Theophylline on the Risk of Acute Exacerbations of COPD: the TASCS Randomised Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The George Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Medical Research Council, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The George Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this multi-centre, double blind, randomised, controlled trial (DBRCT) is to assess&#xD;
      the effect of low dose theophylline, singly and in combination with low dose oral prednisone,&#xD;
      on COPD (Chronic Obstructive Pulmonary Disease) exacerbations, quality of life and secondary&#xD;
      clinical outcomes compared with usual therapy and placebo over 48 weeks of treatment. 1670&#xD;
      symptomatic patients with COPD will be recruited in China for comparison of low dose&#xD;
      theophylline versus placebo and low dose theophylline + low dose prednisone The primary&#xD;
      end-point for this study is the annualised COPD exacerbation rate between the treatment&#xD;
      groups. Secondary outcomes included time to first severe exacerbation requiring&#xD;
      hospitalisation or death, health status, and pre- and post-bronchodilator spirometry.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators hypothesise that patients with COPD will have beneficial responses to low&#xD;
      dose theophylline and prednisone, superior to placebo and low dose theophylline alone,&#xD;
      reflected by a range of clinical outcomes.&#xD;
&#xD;
      The study aims to demonstrate that treatment with low dose oral prednisone and low dose, slow&#xD;
      release theophylline compared to low dose, slow release theophylline only or placebo will&#xD;
      reduce COPD exacerbations and improve a range of secondary outcomes including quality of&#xD;
      life, COPD Assessment Test (CAT) score, hospital admissions and lung function.&#xD;
&#xD;
      Eligible participants will be randomised to one of three treatment arms in a DBRCT and will&#xD;
      receive placebo OR low-dose theophylline (100 mg twice a day) OR low-dose theophylline 100 mg&#xD;
      twice a day (BD) plus low-dose prednisone (5 mg once a day)&#xD;
&#xD;
      Patients will be eligible for inclusion if all the following criteria are met:&#xD;
&#xD;
        -  Current or former smokers (&gt;10 pack years) or biomass exposure&#xD;
&#xD;
        -  40 - 80 years of age&#xD;
&#xD;
        -  Clinical diagnosis of COPD&#xD;
&#xD;
        -  Post-bronchodilator forced expiratory volume at one second (FEV1) &lt;70% predicted&#xD;
&#xD;
        -  Post bronchodilator FEV1/forced vital capacity (FVC) ratio&lt;0.7&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2014</start_date>
  <completion_date type="Actual">May 14, 2018</completion_date>
  <primary_completion_date type="Actual">May 14, 2018</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total COPD Exacerbation Rate</measure>
    <time_frame>48 weeks observation; rate annualised</time_frame>
    <description>The total number of COPD exacerbations reported within 48 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to First COPD Exacerbation</measure>
    <time_frame>Median time (days) from randomisation to first exacerbation over a 48 week period per participant</time_frame>
    <description>The median time (days) from randomisation to first exacerbation per participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)</measure>
    <time_frame>Change over 48 week study duration</time_frame>
    <description>THe St. George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post Bronchodilator FEV1</measure>
    <time_frame>Change at 48 weeks</time_frame>
    <description>The change in post bronchodilator FEV1 from baseline to 48 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in COPD Assessment Test (CAT) Score</measure>
    <time_frame>48 weeks</time_frame>
    <description>The COPD Assessment Test (CAT) is a patient-completed questionnaire assessing globally the impact of COPD (cough, sputum, dysnea, chest tighteness) on health status. The range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. The outcome measure is assessing the change in score from baseline to 48 weeks. A negative change denotes an improvement in health status.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hospitalisations</measure>
    <time_frame>48 weeks</time_frame>
    <description>The total number of hospitalisation events within 48 weeks</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1670</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-dose theophylline arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Theophylline 100 mg twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Theophylline and Prednisone arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Theophylline</intervention_name>
    <description>Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor</description>
    <arm_group_label>Low-dose theophylline arm</arm_group_label>
    <arm_group_label>Theophylline and Prednisone arm</arm_group_label>
    <other_name>Theophylline (100 mg twice a day)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
    <arm_group_label>Theophylline and Prednisone arm</arm_group_label>
    <other_name>Prednisone (5mg once daily)</other_name>
    <other_name>cortisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for prednisone)</intervention_name>
    <description>Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
    <arm_group_label>Low-dose theophylline arm</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Prednisone placebo 1 tab once daily in arms 1 and 2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for Theophylline)</intervention_name>
    <description>One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Theophylline placebo 1 tab twice daily</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current or former smokers (&gt; 10 pack years) or biomass exposure&#xD;
&#xD;
          -  40 - 80 years of age&#xD;
&#xD;
          -  Clinical diagnosis of COPD&#xD;
&#xD;
          -  Post-bronchodilator FEV1 &lt; 70% predicted&#xD;
&#xD;
          -  Post bronchodilator FEV1/FVC ratio &lt; 0.7&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Life expectancy of less than 12 months&#xD;
&#xD;
          -  Exacerbation or respiratory infection within 4 weeks prior to randomisation&#xD;
&#xD;
          -  Patient is taking and requires maintenance oral corticosteroids&#xD;
&#xD;
          -  Patient is on domiciliary oxygen&#xD;
&#xD;
          -  There has been previous pulmonary resection&#xD;
&#xD;
          -  Previous sensitivity to, or intolerance of theophylline&#xD;
&#xD;
          -  Coexistent illness precluding participation in the study (epilepsy, chronic liver&#xD;
             disease, unstable cardiovascular disease, diabetes, active malignancy)&#xD;
&#xD;
          -  Inability to complete quality of life questionnaire&#xD;
&#xD;
          -  Concomitant major illness that would interfere with visits, assessments and follow-up&#xD;
&#xD;
          -  Have evidence of chronic liver disease, or transaminase or gamma-glutamyltransferase&#xD;
             (GGT) elevation &gt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Random blood glucose level &gt; 8mmol/L&#xD;
&#xD;
          -  High chance in the view of the treating physician that the patient will not adhere to&#xD;
             study treatment and follow up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Norbert Berend, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The George Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christine R Jenkins, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The George Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The George Institute for Global Health</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>May 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <results_first_submitted>June 21, 2021</results_first_submitted>
  <results_first_submitted_qc>August 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 12, 2021</results_first_posted>
  <last_update_submitted>August 10, 2021</last_update_submitted>
  <last_update_submitted_qc>August 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>Theophylline</keyword>
  <keyword>Oral corticosteroids</keyword>
  <keyword>COPD exacerbations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <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>Prednisone</mesh_term>
    <mesh_term>Cortisone</mesh_term>
    <mesh_term>Theophylline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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 27, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT02261727/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>September 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT02261727/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Low-dose Theophylline Arm</title>
          <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 twice daily + prednisone placebo 1 once daily)</description>
        </group>
        <group group_id="P3">
          <title>Theophylline and Prednisone Arm</title>
          <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="568"/>
                <participants group_id="P2" count="554"/>
                <participants group_id="P3" count="548"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="411"/>
                <participants group_id="P2" count="408"/>
                <participants group_id="P3" count="423"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="157"/>
                <participants group_id="P2" count="146"/>
                <participants group_id="P3" count="125"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
        </group>
        <group group_id="B2">
          <title>Low-dose Theophylline Arm</title>
          <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
        </group>
        <group group_id="B3">
          <title>Theophylline and Prednisone Arm</title>
          <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
        </group>
        <group group_id="B4">
          <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="554"/>
            <count group_id="B2" value="568"/>
            <count group_id="B3" value="548"/>
            <count group_id="B4" value="1670"/>
          </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="63.9" spread="8.5"/>
                    <measurement group_id="B2" value="64.4" spread="7.8"/>
                    <measurement group_id="B3" value="64.9" spread="7.7"/>
                    <measurement group_id="B4" value="64.4" spread="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="128"/>
                    <measurement group_id="B2" value="134"/>
                    <measurement group_id="B3" value="144"/>
                    <measurement group_id="B4" value="406"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="426"/>
                    <measurement group_id="B2" value="434"/>
                    <measurement group_id="B3" value="404"/>
                    <measurement group_id="B4" value="1264"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="554"/>
                    <measurement group_id="B2" value="568"/>
                    <measurement group_id="B3" value="548"/>
                    <measurement group_id="B4" value="1670"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>China</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="554"/>
                    <measurement group_id="B2" value="568"/>
                    <measurement group_id="B3" value="548"/>
                    <measurement group_id="B4" value="1670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Current Smoker</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="98"/>
                    <measurement group_id="B2" value="121"/>
                    <measurement group_id="B3" value="113"/>
                    <measurement group_id="B4" value="332"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pack Years - Current Smoker</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.5" spread="27.1"/>
                    <measurement group_id="B2" value="40.5" spread="22.3"/>
                    <measurement group_id="B3" value="44.4" spread="22.7"/>
                    <measurement group_id="B4" value="42.7" spread="23.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Spirometry - Pre bronchodilator Forced Expiratory Volume in one second (FEV1)</title>
          <units>L/sec</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.0" spread="0.4"/>
                    <measurement group_id="B2" value="1.0" spread="0.4"/>
                    <measurement group_id="B3" value="0.9" spread="0.4"/>
                    <measurement group_id="B4" value="1.0" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total COPD Exacerbation Rate</title>
        <description>The total number of COPD exacerbations reported within 48 weeks</description>
        <time_frame>48 weeks observation; rate annualised</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
          </group>
          <group group_id="O2">
            <title>Low-dose Theophylline Arm</title>
            <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
          </group>
          <group group_id="O3">
            <title>Theophylline and Prednisone Arm</title>
            <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
          </group>
        </group_list>
        <measure>
          <title>Total COPD Exacerbation Rate</title>
          <description>The total number of COPD exacerbations reported within 48 weeks</description>
          <units>Exacerbations per participant year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="554"/>
                <count group_id="O2" value="568"/>
                <count group_id="O3" value="548"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" lower_limit="0.87" upper_limit="1.14"/>
                    <measurement group_id="O2" value="0.86" lower_limit="0.75" upper_limit="0.99"/>
                    <measurement group_id="O3" value="0.89" lower_limit="0.78" upper_limit="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First COPD Exacerbation</title>
        <description>The median time (days) from randomisation to first exacerbation per participant</description>
        <time_frame>Median time (days) from randomisation to first exacerbation over a 48 week period per participant</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
          </group>
          <group group_id="O2">
            <title>Low-dose Theophylline Arm</title>
            <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
          </group>
          <group group_id="O3">
            <title>Theophylline and Prednisone Arm</title>
            <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First COPD Exacerbation</title>
          <description>The median time (days) from randomisation to first exacerbation per participant</description>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="554"/>
                <count group_id="O2" value="568"/>
                <count group_id="O3" value="548"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="137" lower_limit="58.5" upper_limit="233.5"/>
                    <measurement group_id="O2" value="150" lower_limit="66.0" upper_limit="242.0"/>
                    <measurement group_id="O3" value="151" lower_limit="71.0" upper_limit="247.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)</title>
        <description>THe St. George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.</description>
        <time_frame>Change over 48 week study duration</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
          </group>
          <group group_id="O2">
            <title>Low-dose Theophylline Arm</title>
            <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
          </group>
          <group group_id="O3">
            <title>Theophylline and Prednisone Arm</title>
            <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)</title>
          <description>THe St. George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.</description>
          <units>Scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="554"/>
                <count group_id="O2" value="568"/>
                <count group_id="O3" value="548"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.95" spread="0.91"/>
                    <measurement group_id="O2" value="-6.85" spread="0.91"/>
                    <measurement group_id="O3" value="-6.48" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post Bronchodilator FEV1</title>
        <description>The change in post bronchodilator FEV1 from baseline to 48 weeks</description>
        <time_frame>Change at 48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
          </group>
          <group group_id="O2">
            <title>Low-dose Theophylline Arm</title>
            <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
          </group>
          <group group_id="O3">
            <title>Theophylline and Prednisone Arm</title>
            <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
          </group>
        </group_list>
        <measure>
          <title>Post Bronchodilator FEV1</title>
          <description>The change in post bronchodilator FEV1 from baseline to 48 weeks</description>
          <units>L/sec</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="554"/>
                <count group_id="O2" value="568"/>
                <count group_id="O3" value="548"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.01"/>
                    <measurement group_id="O2" value="-0.01" spread="0.01"/>
                    <measurement group_id="O3" value="-0.02" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in COPD Assessment Test (CAT) Score</title>
        <description>The COPD Assessment Test (CAT) is a patient-completed questionnaire assessing globally the impact of COPD (cough, sputum, dysnea, chest tighteness) on health status. The range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. The outcome measure is assessing the change in score from baseline to 48 weeks. A negative change denotes an improvement in health status.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
          </group>
          <group group_id="O2">
            <title>Low-dose Theophylline Arm</title>
            <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
          </group>
          <group group_id="O3">
            <title>Theophylline and Prednisone Arm</title>
            <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
          </group>
        </group_list>
        <measure>
          <title>Change in COPD Assessment Test (CAT) Score</title>
          <description>The COPD Assessment Test (CAT) is a patient-completed questionnaire assessing globally the impact of COPD (cough, sputum, dysnea, chest tighteness) on health status. The range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. The outcome measure is assessing the change in score from baseline to 48 weeks. A negative change denotes an improvement in health status.</description>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="554"/>
                <count group_id="O2" value="568"/>
                <count group_id="O3" value="548"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.29" spread="0.33"/>
                    <measurement group_id="O2" value="-2.77" spread="0.33"/>
                    <measurement group_id="O3" value="-2.57" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Hospitalisations</title>
        <description>The total number of hospitalisation events within 48 weeks</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
          </group>
          <group group_id="O2">
            <title>Low-dose Theophylline Arm</title>
            <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
          </group>
          <group group_id="O3">
            <title>Theophylline and Prednisone Arm</title>
            <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
          </group>
        </group_list>
        <measure>
          <title>Hospitalisations</title>
          <description>The total number of hospitalisation events within 48 weeks</description>
          <units>Number of hospitalisation events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="554"/>
                <count group_id="O2" value="568"/>
                <count group_id="O3" value="548"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="120"/>
                    <measurement group_id="O2" value="101"/>
                    <measurement group_id="O3" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from all participants over the 48 weeks of the intervention period.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
Placebo (for Theophylline): One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)</description>
        </group>
        <group group_id="E2">
          <title>Low-dose Theophylline Arm</title>
          <description>Theophylline 100 mg twice daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Placebo (for prednisone): - Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily&#xD;
- Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily</description>
        </group>
        <group group_id="E3">
          <title>Theophylline and Prednisone Arm</title>
          <description>Theophylline 100 mg twice daily plus prednisone 5 mg once daily&#xD;
Theophylline: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor&#xD;
Prednisone: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (1701)</default_vocab>
        <default_assessment>Non-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="3" subjects_at_risk="554"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="568"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="548"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="96" subjects_at_risk="554"/>
                <counts group_id="E2" subjects_affected="91" subjects_at_risk="568"/>
                <counts group_id="E3" subjects_affected="83" subjects_at_risk="548"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COPD Exacerbation - Hospitalised</sub_title>
                <counts group_id="E1" events="135" subjects_affected="96" subjects_at_risk="554"/>
                <counts group_id="E2" events="102" subjects_affected="91" subjects_at_risk="568"/>
                <counts group_id="E3" events="115" subjects_affected="83" subjects_at_risk="548"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="196" subjects_at_risk="554"/>
                <counts group_id="E2" subjects_affected="222" subjects_at_risk="568"/>
                <counts group_id="E3" subjects_affected="202" subjects_at_risk="548"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COPD Exacerbation - not hospitalised</sub_title>
                <counts group_id="E1" events="306" subjects_affected="168" subjects_at_risk="554"/>
                <counts group_id="E2" events="290" subjects_affected="181" subjects_at_risk="568"/>
                <counts group_id="E3" events="306" subjects_affected="173" subjects_at_risk="548"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="37" subjects_affected="28" subjects_at_risk="554"/>
                <counts group_id="E2" events="54" subjects_affected="41" subjects_at_risk="568"/>
                <counts group_id="E3" events="34" subjects_affected="29" subjects_at_risk="548"/>
              </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>All papers will be authored by all or a subgroup of members of the TASCS Publications Committee. Publications prior to the primary and major secondary papers may only be initiated by the Publications Committee. Publications subsequent to the primary and major secondary papers may be authored by individually named authors, and may at the request of the Publication Committee be required to include the annotation &quot;On behalf of the Theophylline and Steroids in COPD (TASCS) trial investigators&quot;.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>There are some limitations to our study, there was a 26% withdrawal rate in this study, with a higher rate of withdrawals occurring earlier in the trial. Patients requested withdrawal if they felt the treatment was not helping them and, in particular, if they suffered an exacerbation. This was most evident at the first study visit after treatment commencement, when the greatest number of withdrawals occurred.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Prof Christine Jenkins</name_or_title>
      <organization>The George Institute for Global Health</organization>
      <phone>+61280524300</phone>
      <email>christine.jenkins@sydney.edu.au</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/NCT02261727
org study id: TGI-Resp-01
secondary id: 1033117
nct id: NCT02261727
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this multi-centre, double blind, randomised, controlled trial (DBRCT) is to assess
      the effect of low dose theophylline, singly and in combination with low dose oral prednisone,
      on COPD (Chronic Obstructive Pulmonary Disease) exacerbations, quality of life and secondary
      clinical outcomes compared with usual therapy and placebo over 48 weeks of treatment. 1670
      symptomatic patients with COPD will be recruited in China for comparison of low dose
      theophylline versus placebo and low dose theophylline + low dose prednisone The primary
      end-point for this study is the annualised COPD exacerbation rate between the treatment
      groups. Secondary outcomes included time to first severe exacerbation requiring
      hospitalisation or death, health status, and pre- and post-bronchodilator spirometry.
The investigators hypothesise that patients with COPD will have beneficial responses to low
      dose theophylline and prednisone, superior to placebo and low dose theophylline alone,
      reflected by a range of clinical outcomes.

      The study aims to demonstrate that treatment with low dose oral prednisone and low dose, slow
      release theophylline compared to low dose, slow release theophylline only or placebo will
      reduce COPD exacerbations and improve a range of secondary outcomes including quality of
      life, COPD Assessment Test (CAT) score, hospital admissions and lung function.

      Eligible participants will be randomised to one of three treatment arms in a DBRCT and will
      receive placebo OR low-dose theophylline (100 mg twice a day) OR low-dose theophylline 100 mg
      twice a day (BD) plus low-dose prednisone (5 mg once a day)

      Patients will be eligible for inclusion if all the following criteria are met:

        -  Current or former smokers (>10 pack years) or biomass exposure

        -  40 - 80 years of age

        -  Clinical diagnosis of COPD

        -  Post-bronchodilator forced expiratory volume at one second (FEV1) <70% predicted

        -  Post bronchodilator FEV1/forced vital capacity (FVC) ratio<0.7
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Total COPD Exacerbation Rate
time frame: 48 weeks observation; rate annualised
description: The total number of COPD exacerbations reported within 48 weeks
measure: Time to First COPD Exacerbation
time frame: Median time (days) from randomisation to first exacerbation over a 48 week period per participant
description: The median time (days) from randomisation to first exacerbation per participant
measure: Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)
time frame: Change over 48 week study duration
description: THe St. George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations.
measure: Post Bronchodilator FEV1
time frame: Change at 48 weeks
description: The change in post bronchodilator FEV1 from baseline to 48 weeks
measure: Change in COPD Assessment Test (CAT) Score
time frame: 48 weeks
description: The COPD Assessment Test (CAT) is a patient-completed questionnaire assessing globally the impact of COPD (cough, sputum, dysnea, chest tighteness) on health status. The range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life. The outcome measure is assessing the change in score from baseline to 48 weeks. A negative change denotes an improvement in health status.
measure: Hospitalisations
time frame: 48 weeks
description: The total number of hospitalisation events within 48 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo theophylline, one tablet twice daily, and Placebo prednisone, one tablet once daily
arm group label: Low-dose theophylline arm
arm group type: Active Comparator
description: Theophylline 100 mg twice daily
arm group label: Theophylline and Prednisone arm
arm group type: Active Comparator
description: Theophylline 100 mg twice daily plus prednisone 5 mg once daily
intervention type: Drug
intervention name: Theophylline
description: Theophylline is an oral methylxanthine which relaxes smooth muscle through its action as a phosphodiesterase inhibitor
arm group label: Low-dose theophylline arm
arm group label: Theophylline and Prednisone arm
other name: Theophylline (100 mg twice a day)
intervention type: Drug
intervention name: Prednisone
description: Prednisone is an oral glucocorticosteroid which has anti-inflammatory properties
arm group label: Theophylline and Prednisone arm
other name: Prednisone (5mg once daily)
other name: cortisone
intervention type: Drug
intervention name: Placebo (for prednisone)
description: Arm 1 : Theophylline Placebo 1 tab twice daily and Prednisone placebo 1 tab once daily
Arm 2 : Theophylline 100mg 1 tab twice daily and Prednisone placebo 1 tab once daily
arm group label: Low-dose theophylline arm
arm group label: Placebo
other name: Prednisone placebo 1 tab once daily in arms 1 and 2
intervention type: Drug
intervention name: Placebo (for Theophylline)
description: One tablet twice daily in arm 1 (theophylline placebo 1 BD + prednisone placebo 1 once daily)
arm group label: Placebo
other name: Theophylline placebo 1 tab twice daily
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Norbert Berend, MD
role: Principal Investigator
affiliation: The George Institute
last name: Christine R Jenkins, MD
role: Principal Investigator
affiliation: The George Institute
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Prednisone
mesh term: Cortisone
mesh term: Theophylline
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There are some limitations to our study, there was a 26% withdrawal rate in this study, with a higher rate of withdrawals occurring earlier in the trial. Patients requested withdrawal if they felt the treatment was not helping them and, in particular, if they suffered an exacerbation. This was most evident at the first study visit after treatment commencement, when the greatest number of withdrawals occurred.
point of contact: 