<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/NCT01696214</url>
  </required_header>
  <id_info>
    <org_study_id>ARCTC-09</org_study_id>
    <secondary_id>IR34HL109482-01A1</secondary_id>
    <nct_id>NCT01696214</nct_id>
  </id_info>
  <brief_title>A Pilot Study to Determine the Feasibility and Utility of Implementing of the Full Scale TOM Trial</brief_title>
  <acronym>SAPS</acronym>
  <official_title>SAPS:Smoking Asthmatics Pilot Study:</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of the pilot (SAPS) protocol is to determine the feasibility and utility of&#xD;
      implementing the provisional design of the full scale TOM trial (e.g., the six month&#xD;
      treatment period, the impact of the smoking cessation intervention).&#xD;
&#xD;
      There is no active hypothesis for the Vanguard Protocol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The protocol is a small scale pilot of the full-scale TOM trial, and it will utilize a&#xD;
      placebo design and incorporates 4 treatment arms. In the Vanguard Protocol all participants&#xD;
      are to complete a 4 week run-in with Advair 100/50, followed by randomization to 1 of 4 arms&#xD;
      of study treatment. The 4 drug treatment combinations are (2 inhalers, 2 pills):&#xD;
&#xD;
        -  Advair 250/50, Placebo, Placebo, Placebo&#xD;
&#xD;
        -  Advair 100/50 and montelukast, Placebo, Placebo&#xD;
&#xD;
        -  Advair 100/50 and theophylline, Placebo, Placebo&#xD;
&#xD;
        -  Advair 100/50 and ipratropium, Placebo, Placebo The 24 week treatment phase will be&#xD;
           followed by a 4 week washout period on Advair 100/50. There is no crossover.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">May 2015</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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Asthma Control Test</measure>
    <time_frame>Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and at follow-up visit 1 month off study drug. Median scores over the 24 weeks of treatment were compared.</time_frame>
    <description>The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score &lt;16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Asthma Symptom Utility Index (ASUI)</measure>
    <time_frame>Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and a follow-up visit 1 month off study drug. Median scores, change from initial visit and end of treatment, were compared</time_frame>
    <description>The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent (%) Perdicted FEV1 Changes</measure>
    <time_frame>Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks. Median scores over the 24 weeks of treatment were compared</time_frame>
    <description>Physiologic measures of % predicted FEV1</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Ipratropium</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Theophylline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Montelukast</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>fluticasone 250 mg/salmeterol 50mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone 250 mg/salmeterol 50 mg</intervention_name>
    <description>Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo</description>
    <arm_group_label>fluticasone 250 mg/salmeterol 50mg</arm_group_label>
    <other_name>Advair(fluticasone/salmeterol)250/50</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Montelukast 10mg</intervention_name>
    <description>Participants will be assigned to montelukast once a day for 24 weeks.</description>
    <arm_group_label>Montelukast</arm_group_label>
    <other_name>Singulair</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Theophylline 400 mg</intervention_name>
    <description>Participants will be assigned to theophylline once a day for 24 weeks</description>
    <arm_group_label>Theophylline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ipratropium</intervention_name>
    <description>Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.</description>
    <arm_group_label>Ipratropium</arm_group_label>
    <other_name>Atrovent</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Gender and Age:&#xD;
&#xD;
          -  Males and females, ages 18- 50&#xD;
&#xD;
        Current Smoker:&#xD;
&#xD;
          -  Smoke at least 5 cigarettes per day for at least 5 years&#xD;
&#xD;
          -  Positive urine cotinine test&#xD;
&#xD;
        Asthma:&#xD;
&#xD;
          -  Physician diagnosed asthma&#xD;
&#xD;
          -  Symptomatic, as evidenced by&#xD;
&#xD;
               -  Use of SABA two or more times per week for relief of asthma symptoms, or&#xD;
&#xD;
               -  One or more nocturnal awakenings per week for asthma symptoms ACRC - SC MEETING -&#xD;
                  19 MAY 2012 SAPS │ 25 Confidential, not for attribution or citation.&#xD;
&#xD;
          -  Pre-BD FEV1 greater than or equal to 40% predicted&#xD;
&#xD;
          -  Asthma diagnosis confirmed by either&#xD;
&#xD;
               -  albuterol reversibility of FEV1 by 12% or more, or&#xD;
&#xD;
               -  20% fall in FEV1 at 8mg or less of methacholine&#xD;
&#xD;
          -  If over age 45, a DLco greater than 80% predicted&#xD;
&#xD;
          -  Females of childbearing potential: not pregnant, not lactating and agree to practice&#xD;
             an adequate birth control method (abstinence, combination barrier and spermicide, or&#xD;
             hormonal) for the duration of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of COPD or emphysema&#xD;
&#xD;
          -  Other major chronic illnesses in the opinion of the investigator that might interfere&#xD;
             with the study:&#xD;
&#xD;
             - e.g. including but not limited to uncontrolled diabetes, uncontrolled HIV infection&#xD;
             or other immune system disorder, hyperthyroidism, seizure disorders, renal failure,&#xD;
             liver disease, non-skin cancer, unstable psychiatric illness.&#xD;
&#xD;
          -  Recent active substance abuse (in past 6 months)&#xD;
&#xD;
          -  Lung disease other than asthma including COPD, bronchiectasis, sarcoidosis, or other&#xD;
             significant lung disease&#xD;
&#xD;
          -  Unstable cardiac disease (decompensated CHF, unstable angina, recent MI, atrial&#xD;
             fibrillation, supraventricular or ventricular tachycardia, congenital heart disease,&#xD;
             or severe uncontrolled hypertension).&#xD;
&#xD;
          -  High risk of near fatal or fatal asthma as defined by the following 1-3&#xD;
&#xD;
               -  ICU admission of asthma in the past year&#xD;
&#xD;
               -  more than 2 hospitalizations for asthma in the previous year&#xD;
&#xD;
               -  more than 3 ED visits for asthma in the previous year&#xD;
&#xD;
               -  intubation or ICU admission for asthma in the past 2 years&#xD;
&#xD;
               -  use of more than 2 canisters of inhaled short-acting beta2-agonist in past month&#xD;
&#xD;
          -  Acute asthma exacerbation in the past 4 weeks (treatment with systemic&#xD;
             corticosteroids)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joe Ramsdell, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSD</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Airway Research &amp; Clinical Trials Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>June 25, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>August 8, 2016</results_first_submitted>
  <results_first_submitted_qc>October 3, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 12, 2016</results_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Joe Ramsdell</investigator_full_name>
    <investigator_title>Medical Doctor</investigator_title>
  </responsible_party>
  <keyword>asthma,smokers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
    <mesh_term>Theophylline</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
    <mesh_term>Ipratropium</mesh_term>
    <mesh_term>Fluticasone-Salmeterol Drug Combination</mesh_term>
    <mesh_term>Montelukast</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>results will be presented been publication four-minute meetings</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Ipratropium</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and placebo montelukast.&#xD;
Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times</description>
        </group>
        <group group_id="P2">
          <title>Theophylline</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.&#xD;
Theophylline: Participants will be assigned to theophylline 400 mg once a day for 24 weeks</description>
        </group>
        <group group_id="P3">
          <title>Montelukast</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.&#xD;
Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.</description>
        </group>
        <group group_id="P4">
          <title>Fluticasone 250 mg/Salmeterol 50mg</title>
          <description>Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.&#xD;
Fluticasone 250 mg/salmeterol 50 mg:&#xD;
Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>smoking asthmatics</population>
      <group_list>
        <group group_id="B1">
          <title>Ipratropium</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and montelukast.&#xD;
Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times</description>
        </group>
        <group group_id="B2">
          <title>Theophylline</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 300 mg once a day for 24 weeks with placebo tiotroprium and montelukast.&#xD;
Theophylline: Participants will be assigned to theophylline 300 mg once a day for 24 weeks</description>
        </group>
        <group group_id="B3">
          <title>Montelukast</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and tiotroprium.&#xD;
Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.</description>
        </group>
        <group group_id="B4">
          <title>Fluticasone 250 mg/Salmeterol 50mg</title>
          <description>Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, tiotroprium, and montelukast.&#xD;
Fluticasone 250 mg/salmeterol 50 mg:&#xD;
Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50</description>
        </group>
        <group group_id="B5">
          <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="4"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="19"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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 group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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 group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49" lower_limit="42" upper_limit="50"/>
                    <measurement group_id="B2" value="48" lower_limit="44" upper_limit="50"/>
                    <measurement group_id="B3" value="39" lower_limit="28" upper_limit="50"/>
                    <measurement group_id="B4" value="28" lower_limit="26" upper_limit="50"/>
                    <measurement group_id="B5" value="41" lower_limit="26" upper_limit="50"/>
                  </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="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="9"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Asthma Control Test</title>
        <description>The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score &lt;16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3.</description>
        <time_frame>Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and at follow-up visit 1 month off study drug. Median scores over the 24 weeks of treatment were compared.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ipratropium</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and montelukast.&#xD;
ipratropium: Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Theophylline</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and montelukast.&#xD;
Theophylline 400 mg: Participants will be assigned to Theophylline once a day for 24 weeks</description>
          </group>
          <group group_id="O3">
            <title>Montelukast</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and ipratropium.&#xD;
Montelukast 10mg: Participants will be assigned to Leukotriene receptor antagonist once a day for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone 250 mg/Salmeterol 50mg</title>
            <description>Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, ipratropium, and montelukast.&#xD;
Fluticasone 250 mg/salmeterol 50 mg: Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Asthma Control Test</title>
          <description>The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score &lt;16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.5" lower_limit="13" upper_limit="19"/>
                    <measurement group_id="O2" value="13" lower_limit="7" upper_limit="19"/>
                    <measurement group_id="O3" value="12" lower_limit="9" upper_limit="15"/>
                    <measurement group_id="O4" value="10" lower_limit="5" upper_limit="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Asthma Symptom Utility Index (ASUI)</title>
        <description>The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation.</description>
        <time_frame>Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and a follow-up visit 1 month off study drug. Median scores, change from initial visit and end of treatment, were compared</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ipratropium</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast.&#xD;
ipratropium: Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Theophylline</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.&#xD;
Theophylline 400 mg: Participants will be assigned to theophylline once a day for 24 weeks</description>
          </group>
          <group group_id="O3">
            <title>Montelukast</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.&#xD;
Montelukast 10mg: Participants will be assigned to montelukast once a day for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone 250 mg/Salmeterol 50mg</title>
            <description>Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.&#xD;
Fluticasone 250 mg/salmeterol 50 mg: Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo</description>
          </group>
        </group_list>
        <measure>
          <title>The Asthma Symptom Utility Index (ASUI)</title>
          <description>The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" spread="0.07"/>
                    <measurement group_id="O2" value="0.24" spread="0.20"/>
                    <measurement group_id="O3" value="0.14" spread="0.15"/>
                    <measurement group_id="O4" value="0.13" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent (%) Perdicted FEV1 Changes</title>
        <description>Physiologic measures of % predicted FEV1</description>
        <time_frame>Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks. Median scores over the 24 weeks of treatment were compared</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ipratropium</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and placebo montelukast.&#xD;
Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times</description>
          </group>
          <group group_id="O2">
            <title>Theophylline</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.&#xD;
Theophylline: Participants will be assigned to theophylline 400 mg once a day for 24 weeks</description>
          </group>
          <group group_id="O3">
            <title>Montelukast</title>
            <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.&#xD;
Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone 250 mg/Salmeterol 50mg</title>
            <description>Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.&#xD;
Fluticasone 250 mg/salmeterol 50 mg:&#xD;
Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Perdicted FEV1 Changes</title>
          <description>Physiologic measures of % predicted FEV1</description>
          <units>percent predicted FEV1</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.62" spread="7.89"/>
                    <measurement group_id="O2" value="4.73" spread="7.72"/>
                    <measurement group_id="O3" value="0.87" spread="10.57"/>
                    <measurement group_id="O4" value="-5.71" spread="5.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ipratropium</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 0.02% solution, 2.5 ml via mini nebulizer for 24 weeks with placebo theophylline and montelukast.&#xD;
Ipratropium: Participants will be assigned to ipratropium 0.02% solution, 2.5 ml via mini nebulizer 3 times</description>
        </group>
        <group group_id="E2">
          <title>Theophylline</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 300 mg once a day for 24 weeks with placebo tiotroprium and montelukast.&#xD;
Theophylline: Participants will be assigned to theophylline 300 mg once a day for 24 weeks</description>
        </group>
        <group group_id="E3">
          <title>Montelukast</title>
          <description>Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and tiotroprium.&#xD;
Montelukast 10mg: Participants will be assigned to montelukast 10 mg once a day for 24 weeks.</description>
        </group>
        <group group_id="E4">
          <title>Fluticasone 250 mg/Salmeterol 50mg</title>
          <description>Participants will be assigned to inhaled fluticasone 250 mg/salmeterol 50 mg twice a day for 24 weeks with placebo theophylline, tiotroprium, and montelukast.&#xD;
Fluticasone 250 mg/salmeterol 50 mg:&#xD;
Participants will be assigned to a 24 week treatment with inhaled fluticasone 250 mg /salmeterol 50</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>asthma exacerbation</sub_title>
                <description>Participant hospitalized overnight with asthma exacerbation. Study drug stopped while overnight hospitalization and continued with randomized study drug and completed double blind portion of study.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>death</sub_title>
                <description>Participant in the run-out phase with open label Advair 100/50 and was found dead. Autopsy found cause of that to be due to Phencyclidine and Cocaine Toxicity</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="4" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>tachycardia</sub_title>
                <description>transient tachycardia</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>iritis</sub_title>
                <description>transient viral</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <description>transient nausea</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <description>transient diarrhea</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <description>transient constipation</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>drowsiness</sub_title>
                <description>transient drowsiness</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>dry mouth</sub_title>
                <description>transient dry mouth</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>edema</sub_title>
                <description>mild transient edema</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>viral infection</sub_title>
                <description>self-limiting viral infection</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>back pain</sub_title>
                <description>transient back pain</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <description>transient chest wall discomfort</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <description>musculoskeletal headache</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>swollen hand</sub_title>
                <description>transient swollen hand</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>sprained finger</sub_title>
                <description>sprained finger, recovered without difficulty</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>migraine headache</sub_title>
                <description>migraine headache</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>urinary tract infection</sub_title>
                <description>treated urinary tract infection with no recurrence</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>rash</sub_title>
                <description>transient rash</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>skin lesion</sub_title>
                <description>stable keratosis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>pruritus</sub_title>
                <description>transient lower extremity itching</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>motor vehicle accident</sub_title>
                <description>motor vehicle accident with no serious injury</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Joe Ramsdell</name_or_title>
      <organization>University of California San Diego</organization>
      <phone>619-543-7241</phone>
      <email>jramsdell@ucsd.edu</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/NCT01696214
org study id: ARCTC-09
secondary id: IR34HL109482-01A1
nct id: NCT01696214
lead sponsor: 
collaborator: 
has dmc: Yes
The primary aim of the pilot (SAPS) protocol is to determine the feasibility and utility of
      implementing the provisional design of the full scale TOM trial (e.g., the six month
      treatment period, the impact of the smoking cessation intervention).

      There is no active hypothesis for the Vanguard Protocol.
The protocol is a small scale pilot of the full-scale TOM trial, and it will utilize a
      placebo design and incorporates 4 treatment arms. In the Vanguard Protocol all participants
      are to complete a 4 week run-in with Advair 100/50, followed by randomization to 1 of 4 arms
      of study treatment. The 4 drug treatment combinations are (2 inhalers, 2 pills):

        -  Advair 250/50, Placebo, Placebo, Placebo

        -  Advair 100/50 and montelukast, Placebo, Placebo

        -  Advair 100/50 and theophylline, Placebo, Placebo

        -  Advair 100/50 and ipratropium, Placebo, Placebo The 24 week treatment phase will be
           followed by a 4 week washout period on Advair 100/50. There is no crossover.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Asthma Control Test
time frame: Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and at follow-up visit 1 month off study drug. Median scores over the 24 weeks of treatment were compared.
description: The primary symptomatic measure, the Asthma Control Test (ACT), has been shown to be valid for measuring poor asthma control in asthmatic children and non-smoking adults. The ACT is a tool developed by Nathan and collaborators a decade ago for evaluating asthma control. It consists of five questions with five possible answers each. A maximum score of 25 points indicates complete asthma control. A score between 20 and 24 represents partially controlled asthma, while a score 19 or below indicates poorly controlled asthma and a score <16 indicates uncontrolled asthma. The minimally important clinical difference has been determined to be 3.
measure: The Asthma Symptom Utility Index (ASUI)
time frame: Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks and a follow-up visit 1 month off study drug. Median scores, change from initial visit and end of treatment, were compared
description: The Asthma Symptom Utility Index (ASUI), an important secondary outcome in the proposed full-scale TOM Trial, has also been shown to be useful in tracking the frequency and severity of asthma-related symptoms in non-smoking asthmatics. ASUI is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. 11 items are reviewed, with 2-week recall to assess four symptoms (cough, wheeze, shortness of breath, and awakening at night) and medication side-effects each on two dimensions (frequency and severity). 4-point Likert scale is used to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe). Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The change between two time points, initial visit and after 24 weeks of treatment, is reported. The median value is reported with the standard deviation.
measure: Percent (%) Perdicted FEV1 Changes
time frame: Outcome measure was assessed at the initial visit, at randomization following a wash-in period of 1 month, monthly for 24 weeks. Median scores over the 24 weeks of treatment were compared
description: Physiologic measures of % predicted FEV1
arm group label: Ipratropium
arm group type: Placebo Comparator
description: Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast.
arm group label: Theophylline
arm group type: Placebo Comparator
description: Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.
arm group label: Montelukast
arm group type: Placebo Comparator
description: Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.
arm group label: fluticasone 250 mg/salmeterol 50mg
arm group type: Placebo Comparator
description: Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.
intervention type: Drug
intervention name: Fluticasone 250 mg/salmeterol 50 mg
description: Drug: Fluticasone 250 mg/salmeterol 50 mg Participants will be assigned to a 24 week treatment with inhaled fluticasone/salmeterol or matching placebo
arm group label: fluticasone 250 mg/salmeterol 50mg
other name: Advair(fluticasone/salmeterol)250/50
intervention type: Drug
intervention name: Montelukast 10mg
description: Participants will be assigned to montelukast once a day for 24 weeks.
arm group label: Montelukast
other name: Singulair
intervention type: Drug
intervention name: Theophylline 400 mg
description: Participants will be assigned to theophylline once a day for 24 weeks
arm group label: Theophylline
intervention type: Drug
intervention name: ipratropium
description: Participants will be assigned to ipratropium 2.5 mL of 0.02% solution via mini nebulizer 3 times a day day for 24 weeks.
arm group label: Ipratropium
other name: Atrovent
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Joe Ramsdell, MD
role: Principal Investigator
affiliation: UCSD
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Joe Ramsdell
investigator title: Medical Doctor
mesh term: Asthma
mesh term: Fluticasone
mesh term: Xhance
mesh term: Theophylline
mesh term: Salmeterol Xinafoate
mesh term: Ipratropium
mesh term: Fluticasone-Salmeterol Drug Combination
mesh term: Montelukast
sharing ipd: Yes
ipd description: results will be presented been publication four-minute meetings
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 