<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/NCT01691885</url>
  </required_header>
  <id_info>
    <org_study_id>116601</org_study_id>
    <nct_id>NCT01691885</nct_id>
  </id_info>
  <brief_title>RELOVAIR® Lung Deflation Study</brief_title>
  <official_title>A Randomised, Double-Blind, Placebo-Controlled, Cross-Over, Single-Centre Study to Investigate the Acute Lung Deflation Effects of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg Once Daily on Cardiac Biventricular Function and Arterial Stiffness in Adults With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <brief_summary>
    <textblock>
      The primary objective of the study is to test the hypothesis that lung hyperinflation&#xD;
      contributes to cardiac dysfunction in COPD and that the treatment of lung deflation with&#xD;
      FF/VI Inhalation Powder 100/25 mcg administered once daily (QD) will result in the reversal&#xD;
      of this cardiac dysfunction compared with placebo. This will be assessed by measures of right&#xD;
      and left global and regional systolic and diastolic cardiac function as assessed using a 30&#xD;
      minute CMR.&#xD;
&#xD;
      A secondary objective will be to investigate the effect of FF/VI inhalation powder 100/25mcg&#xD;
      QD on measures of arterial stiffness in the form of pulse wave analysis and distensability in&#xD;
      the pulmonary and systemic circulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a Phase IIIb, randomised, double-blind, placebo-controlled, cross-over,&#xD;
      single-centre study to investigate the acute effects of FF/VI inhalation powder 100/25mcg QD&#xD;
      in lung deflation on cardiac biventricular function and arterial stiffness in adults with&#xD;
      COPD.&#xD;
&#xD;
      Subjects will visit the clinic a minimum of 4 times over a 28-day period with a further&#xD;
      contact which can be either a telephone contact or clinic visit (Visit/Contact 4). A 7-day&#xD;
      run-in period will be followed by two 7-day (maximum 14-day) treatment periods separated by a&#xD;
      7(±2) day wash-out period. The first dose of treatment will be taken the day after&#xD;
      randomisation. A safety Follow-up contact (either visit or telephone) will occur 7(±2) days&#xD;
      post the last treatment day.&#xD;
&#xD;
      Subjects will be prescribed appropriate COPD therapy at the end of Treatment Visit 5, if&#xD;
      required. There are no plans to provide the study drug for compassionate use following study&#xD;
      completion.&#xD;
&#xD;
      It is planned to have 44 completed evaluable subjects. Subjects who withdraw early will be&#xD;
      replaced. In order to ensure 44 evaluable subjects, assuming a 10% protocol deviation rate,&#xD;
      49 subjects will be randomised. The total duration of subject participation, including the&#xD;
      follow-up period, will be approximately 36 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVI) at the End of the Overall Treatment Period</measure>
    <time_frame>Baseline and end of Treatment Period (7 days)</time_frame>
    <description>RVEDVI is a measure of the volume of blood in the right ventricle at the end of diastole, normalized over body surface area and was measured using Cardiac Magnetic Resonance (CMR) imaging. RVEDVI is calculated as the right ventricular end diastolic volume (RDEDV) divided by the body surface area (BSA). The change from Baseline in RVEDVI was analyzed using a mixed model analysis with period, treatment group, and Baseline RVEDVI fitted as fixed effects and participants fitted as a random effect. The Baseline is defined as the assessment performed pre-dose at Day 1 of Treatment Period 1. The change from Baseline is calculated as the RVEDVI value at the end of each treatment period minus the Baseline value. The Per Protocol (PP) Population was comprised of all participants in the modified intent-to-treat (mITT) Population not identified as having deviations considered to impact the primary efficacy analysis.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>A/B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo followed by Fluticasone Furoate Vilanterol Combination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B/A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Fluticasone Furoate Vilanterol Combination followed by Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone Furoate</intervention_name>
    <description>100mcg Once daily</description>
    <arm_group_label>A/B</arm_group_label>
    <arm_group_label>B/A</arm_group_label>
    <other_name>RELOVAIR®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vilanterol</intervention_name>
    <description>25mcg Once daily</description>
    <arm_group_label>A/B</arm_group_label>
    <arm_group_label>B/A</arm_group_label>
    <other_name>RELOVAIR®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type of subject: Outpatient.&#xD;
&#xD;
          -  Informed consent: Subjects must give their signed and dated written informed consent&#xD;
             to participate.&#xD;
&#xD;
          -  Gender: Males or females. Female subjects must be post-menopausal or using a highly&#xD;
             effective method for avoidance of pregnancy. The decision to include or exclude women&#xD;
             of childbearing potential may be made at the discretion of the investigator in&#xD;
             accordance with local practice in relation to adequate contraception.&#xD;
&#xD;
          -  Age 40 and above&#xD;
&#xD;
          -  Smoking history of at least 15 pack years. Previous smokers are defined as those who&#xD;
             have stopped smoking for at least 6 months prior to Visit 1.&#xD;
&#xD;
          -  Established diagnosis of COPD according to ATS/ERS criteria: Subjects with a measured&#xD;
             post-albuterol/salbutamol FEV1 less than 70% of predicted normal values; FEV1/FVC&#xD;
             ratio after bronchodilator less than 0.7; Post-bronchodilator spirometry will be&#xD;
             performed approximately 15 minutes after the subject has self-administered 4&#xD;
             inhalations (i.e., total 400mcg) of salbutamol via an MDI with a valved-holding&#xD;
             chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated; MRC&#xD;
             SCORE greater than 1&#xD;
&#xD;
          -  Residual Volume (RVol) greater than and equal to 20% above predicted value&#xD;
             demonstrating evidence of reversibility post bronchodilator of greater than and equal&#xD;
             to 7.5% predicted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy: Women who are pregnant or lactating.&#xD;
&#xD;
          -  Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of&#xD;
             asthma are eligible if they also have a current diagnosis of COPD).&#xD;
&#xD;
          -  α1-antitrypsin deficiency: Subjects with known α-1 antitrypsin deficiency as the&#xD;
             underlying cause of COPD&#xD;
&#xD;
          -  Other respiratory disorders: Subjects with active tuberculosis or lung cancer as well&#xD;
             as clinically significant bronchiectasis, sarcoidosis, pulmonary fibrosis,&#xD;
             interstitial lung diseases or other active pulmonary diseases. Pulmonary hypertension&#xD;
             from causes other than COPD.&#xD;
&#xD;
          -  Lung resection or transplantation: Subjects with lung volume reduction surgery within&#xD;
             the 12 months prior to Screening or having had a lung transplant or pneumonectomy.&#xD;
&#xD;
          -  A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to&#xD;
             screening and at least 30 days following the last dose of oral corticosteroids (if&#xD;
             applicable).&#xD;
&#xD;
          -  Lower respiratory tract infection: Subjects with lower respiratory tract infection&#xD;
             that required the use of antibiotics within 6 weeks prior to screening.&#xD;
&#xD;
          -  Pulmonary Rehabilitation: Patients to be excluded if they have been in the acute phase&#xD;
             of pulmonary rehabilitation in the 4 weeks prior to screening&#xD;
&#xD;
          -  Current severe heart failure (New York Heart Association class IV) [New York&#xD;
             HeartAssociation, 1994]. Subjects will also be excluded if they have a known ejection&#xD;
             fraction of less than 30%.&#xD;
&#xD;
          -  Abnormal and clinically significant 12-lead ECG&#xD;
&#xD;
          -  Other systemic inflammatory conditions associated with chronic inflammation in the&#xD;
             opinion of the investigator (e.g. rheumatoid arthritis, connective tissue disorders&#xD;
             and Inflammatory Bowel Disease)&#xD;
&#xD;
          -  Other significant diseases / abnormalities: Any life-threatening condition with life&#xD;
             expectancy greater than 1 year, other than vascular disease or COPD, that might&#xD;
             prevent the subject from completing the study.&#xD;
&#xD;
          -  Coronary Artery Bypass Grafting (CABG) in the 6 months prior to screening.&#xD;
&#xD;
          -  Myocardial infarction, cerebrovascular event or coronary artery intervention other&#xD;
             than CABG in the 1 month prior to screening.&#xD;
&#xD;
        Inclusion of these patients with events over 1 month prior to screening will be based on&#xD;
        physician's judgment.&#xD;
&#xD;
          -  History of malignancy within the past 5 years, other than non-melanoma skin cancer.&#xD;
&#xD;
          -  End stage chronic renal disease: Subjects will be excluded if on renal replacement&#xD;
             therapy (hemodialysis or peritoneal). Drug/food allergy: Subjects with a history of&#xD;
             hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroid)&#xD;
             or components of the inhalation powder (e.g. lactose, magnesium stearate). In&#xD;
             addition, patients with a history of severe milk protein allergy that, in the opinion&#xD;
             of the study physician, contraindicates the subject's participation will also be&#xD;
             excluded.&#xD;
&#xD;
          -  Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug&#xD;
             abuse within the last 2 years.&#xD;
&#xD;
          -  Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or&#xD;
             nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen should not&#xD;
             be initiated during the trial.&#xD;
&#xD;
          -  Questionable validity of consent: Subjects with a history of psychiatric disease,&#xD;
             intellectual deficiency, poor motivation or other conditions that will limit the&#xD;
             validity of informed consent to participate in the study or the potential compliance&#xD;
             to study procedures.&#xD;
&#xD;
          -  Additional medication: Use of an investigational device or investigational drug within&#xD;
             30 days or 5 half-lives (whichever is longer) preceding the first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Use of the following medications is not permitted within the following timeframes:&#xD;
             Prohibited Treatment: Depot corticosteroids, Time: 12 weeks; Prohibited Treatment:&#xD;
             Cytochrome P450 3A4 strong inhibitors including but not limited to antiretrovirals&#xD;
             (protease inhibitors) (e.g., indinavir, nelfinavir, ritonavir, saquinavir,&#xD;
             atazanavir); imidazole and triazole anti- fungals (e.g., ketaconazole, itraconazole,&#xD;
             voriconazole); clarithromycin, telithromycin, troleandomycin, mibefradil, cyclosporin,&#xD;
             nefazodone, Time: 6 weeks, Grapefruit is allowed up to Visit 1, then limited to no&#xD;
             more than one glass of grapefruit juice (250 mL/8 ounces) or one grapefruit per day&#xD;
             (The use of cytochrome p450 3A4 inhibitors and inducers in the presence of significant&#xD;
             liver impairment will result in the participant being excluded from the trial);&#xD;
             Prohibited Treatment: Systemic, oral, parenteral (intra-articular) corticosteroids,&#xD;
             Time: 30 days; Prohibited Treatment: Antibiotics, Time: 6 weeks; Prohibited Treatment:&#xD;
             Inhaled corticosteroids, Time: 2 weeks; Inhaled ICS/LABA combination products, Time: 2&#xD;
             weeks; Prohibited Treatment: Long-acting anticholinergics (e.g., tiotropium), Time: 4&#xD;
             days; Prohibited Treatment: PDE-4 inhibitors (e.g., roflumilast), Time: 1 week;&#xD;
             Prohibited Treatment: Oral leukotriene inhibitors (e.g., zafirlukast, montelukast,&#xD;
             zileuton), Time: 48 hours; Prohibited Treatment: Inhaled long acting beta2-agonists&#xD;
             (LABA) (e.g., salmeterol), Time: 48 hours; Prohibited Treatment: Oral beta-agonists,&#xD;
             Time: 48 hours; Prohibited Treatment: Inhaled sodium cromoglycate or nedocromil&#xD;
             sodium, Time: 24 hours; Prohibited Treatment Ipratropium/albuterol (salbutamol)&#xD;
             combination product, Time: 6 hours; Prohibited Treatment: Short-acting&#xD;
             anti-cholinergics (e.g., ipratropium bromide), Time: 6 hours (ipratropium will be&#xD;
             supplied for rescue during the study, in inhaled or nebulized form); Prohibited&#xD;
             Treatment: Theophylline preparations, Time: 48 hours; Prohibited Treatment: Inhaled&#xD;
             short-acting beta2-agonists, Time: 6 hours (albuterol/salbutamol will be supplied for&#xD;
             rescue during the study, in inhaled or nebulized form)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>London</city>
        <zip>E2 9JX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>https://www.clinicalstudydatarequest.com</url>
    <description>Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.</description>
  </link>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>March 26, 2015</results_first_submitted>
  <results_first_submitted_qc>March 26, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 7, 2015</results_first_posted>
  <last_update_submitted>September 26, 2016</last_update_submitted>
  <last_update_submitted_qc>September 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 27, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116601</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
  </study_docs>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>At Visit 1a, participants who met the eligibility criteria stopped their respiratory medication in preparation for their lung volume assessment at screening Visit 1b. At Visit 1b, participants entered a 7(plus or minus 3) day Run-in Period. Overall study duration, following Screening to Follow-up, was 36 days up to a maximum of 54 days.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo Then FF/VI</title>
          <description>Participants entering Treatment Period 1 received matching placebo once daily (QD), each morning via a dry powder inhaler (DPI) for a period of 7 days, up to a maximum of 14 days. Following Treatment Period 1, participants entered a washout period for 7 days, up to a maximum of 9 days. Following the washout period participants entered Treatment Period 2 and received Fluticasone Furoate/Vilanerol (FF/VI) 100/25 micrograms (µg), QD, each morning via a DPI for 7 days, up to a maximum of 14 days.</description>
        </group>
        <group group_id="P2">
          <title>FF/VI Then Placebo</title>
          <description>Participants entering Treatment Period 1 received FF/VI 100/25 µg QD, each morning via a DPI for a period of 7 days, up to a maximum of 14 days. Following Treatment Period 1, participants entered a washout period for 7 days, up to a maximum of 9 days. Following the washout period, participants entered Treatment Period 2 and received matching placebo QD, each morning via a DPI for 7 days, up to a maximum of 14 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1(7-14 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout Period (7-9 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Treatment Period 2 (7-14 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Per Protocol Population</title>
          <description>All participants received placebo or FF/VI 100/25 µg in either of the two treatment periods QD, each morning from a DPI. Treatment periods lasted 7 days up to a maximum of 14 days for each period. The two treatments were separated by a wash out period of 7 days, up to a maximum of 9 days.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="45"/>
          </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="64.4" spread="8.95"/>
                  </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="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>African American/African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - White/Caucasian/European Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVI) at the End of the Overall Treatment Period</title>
        <description>RVEDVI is a measure of the volume of blood in the right ventricle at the end of diastole, normalized over body surface area and was measured using Cardiac Magnetic Resonance (CMR) imaging. RVEDVI is calculated as the right ventricular end diastolic volume (RDEDV) divided by the body surface area (BSA). The change from Baseline in RVEDVI was analyzed using a mixed model analysis with period, treatment group, and Baseline RVEDVI fitted as fixed effects and participants fitted as a random effect. The Baseline is defined as the assessment performed pre-dose at Day 1 of Treatment Period 1. The change from Baseline is calculated as the RVEDVI value at the end of each treatment period minus the Baseline value. The Per Protocol (PP) Population was comprised of all participants in the modified intent-to-treat (mITT) Population not identified as having deviations considered to impact the primary efficacy analysis.</description>
        <time_frame>Baseline and end of Treatment Period (7 days)</time_frame>
        <population>PP Population. Only those participants available at the specified time points were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching placebo once daily (QD), each morning via a dry powder inhaler (DPI) for a period of 7 days, up to a maximum of 14 days during one of the two Treatment Periods. Participants that received placebo in Treatment Period 1, crossed over after the washout period to receive FF/VI 100/25 μg during Treatment Period 2. Participants that received FF/VI 100/25 μg during Treatment Period 1, crossed over after the washout period to receive placebo during Treatment Period 2.</description>
          </group>
          <group group_id="O2">
            <title>FF/VI</title>
            <description>Participants received FF/VI 100/25 μg QD, each morning via a DPI for a period of 7 days, up to a maximum of 14 days during one of the two Treatment Periods. Participants that received FF/VI 100/25 μg in Treatment Period 1, crossed over after the washout period to receive placebo during Treatment Period 2. Participants that received placebo during Treatment Period 1, crossed over after the washout period to receive FF/VI 100/25 μg during Treatment Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVI) at the End of the Overall Treatment Period</title>
          <description>RVEDVI is a measure of the volume of blood in the right ventricle at the end of diastole, normalized over body surface area and was measured using Cardiac Magnetic Resonance (CMR) imaging. RVEDVI is calculated as the right ventricular end diastolic volume (RDEDV) divided by the body surface area (BSA). The change from Baseline in RVEDVI was analyzed using a mixed model analysis with period, treatment group, and Baseline RVEDVI fitted as fixed effects and participants fitted as a random effect. The Baseline is defined as the assessment performed pre-dose at Day 1 of Treatment Period 1. The change from Baseline is calculated as the RVEDVI value at the end of each treatment period minus the Baseline value. The Per Protocol (PP) Population was comprised of all participants in the modified intent-to-treat (mITT) Population not identified as having deviations considered to impact the primary efficacy analysis.</description>
          <population>PP Population. Only those participants available at the specified time points were analyzed</population>
          <units>Milliliter per meter square (mL/m^2)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.47" spread="1.393"/>
                    <measurement group_id="O2" value="5.35" spread="1.365"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <method_desc>Analysis was performed using an ANCOVA model with covariates of treatment, baseline, period and subject as a random effect.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>5.83</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.74</ci_lower_limit>
            <ci_upper_limit>8.91</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and up to the end of treatment (Study Day 23)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received matching placebo once daily (QD), each morning via a dry powder inhaler (DPI) for a period of 7 days, up to a maximum of 14 days during one of the two Treatment Periods. Participants that received placebo in Treatment Period 1, crossed over after the washout period to receive FF/VI 100/25 μg during Treatment Period 2. Participants that received FF/VI 100/25 μg during Treatment Period 1, crossed over after the washout period to receive placebo during Treatment Period 2.</description>
        </group>
        <group group_id="E2">
          <title>FF/VI</title>
          <description>Participants received FF/VI 100/25 μg QD, each morning via a DPI for a period of 7 days, up to a maximum of 14 days during one of the two Treatment Periods. Participants that received FF/VI 100/25 μg in Treatment Period 1, crossed over after the washout period to receive placebo during Treatment Period 2. Participants that received placebo during Treatment Period 1, crossed over after the washout period to receive FF/VI 100/25 μg during Treatment Period 2.</description>
        </group>
      </group_list>
      <serious_events>
        <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="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA 17.0</default_vocab>
        <default_assessment>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="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="44"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
    </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/NCT01691885
org study id: 116601
nct id: NCT01691885
lead sponsor: 
The primary objective of the study is to test the hypothesis that lung hyperinflation
      contributes to cardiac dysfunction in COPD and that the treatment of lung deflation with
      FF/VI Inhalation Powder 100/25 mcg administered once daily (QD) will result in the reversal
      of this cardiac dysfunction compared with placebo. This will be assessed by measures of right
      and left global and regional systolic and diastolic cardiac function as assessed using a 30
      minute CMR.

      A secondary objective will be to investigate the effect of FF/VI inhalation powder 100/25mcg
      QD on measures of arterial stiffness in the form of pulse wave analysis and distensability in
      the pulmonary and systemic circulation.
This will be a Phase IIIb, randomised, double-blind, placebo-controlled, cross-over,
      single-centre study to investigate the acute effects of FF/VI inhalation powder 100/25mcg QD
      in lung deflation on cardiac biventricular function and arterial stiffness in adults with
      COPD.

      Subjects will visit the clinic a minimum of 4 times over a 28-day period with a further
      contact which can be either a telephone contact or clinic visit (Visit/Contact 4). A 7-day
      run-in period will be followed by two 7-day (maximum 14-day) treatment periods separated by a
      7(±2) day wash-out period. The first dose of treatment will be taken the day after
      randomisation. A safety Follow-up contact (either visit or telephone) will occur 7(±2) days
      post the last treatment day.

      Subjects will be prescribed appropriate COPD therapy at the end of Treatment Visit 5, if
      required. There are no plans to provide the study drug for compassionate use following study
      completion.

      It is planned to have 44 completed evaluable subjects. Subjects who withdraw early will be
      replaced. In order to ensure 44 evaluable subjects, assuming a 10% protocol deviation rate,
      49 subjects will be randomised. The total duration of subject participation, including the
      follow-up period, will be approximately 36 days.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVI) at the End of the Overall Treatment Period
time frame: Baseline and end of Treatment Period (7 days)
description: RVEDVI is a measure of the volume of blood in the right ventricle at the end of diastole, normalized over body surface area and was measured using Cardiac Magnetic Resonance (CMR) imaging. RVEDVI is calculated as the right ventricular end diastolic volume (RDEDV) divided by the body surface area (BSA). The change from Baseline in RVEDVI was analyzed using a mixed model analysis with period, treatment group, and Baseline RVEDVI fitted as fixed effects and participants fitted as a random effect. The Baseline is defined as the assessment performed pre-dose at Day 1 of Treatment Period 1. The change from Baseline is calculated as the RVEDVI value at the end of each treatment period minus the Baseline value. The Per Protocol (PP) Population was comprised of all participants in the modified intent-to-treat (mITT) Population not identified as having deviations considered to impact the primary efficacy analysis.
arm group label: A/B
arm group type: Experimental
description: Placebo followed by Fluticasone Furoate Vilanterol Combination
arm group label: B/A
arm group type: Placebo Comparator
description: Fluticasone Furoate Vilanterol Combination followed by Placebo
intervention type: Drug
intervention name: Fluticasone Furoate
description: 100mcg Once daily
arm group label: A/B
arm group label: B/A
other name: RELOVAIR®
intervention type: Drug
intervention name: Vilanterol
description: 25mcg Once daily
arm group label: A/B
arm group label: B/A
other name: RELOVAIR®
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United Kingdom
url: https://www.clinicalstudydatarequest.com
description: Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Fluticasone
mesh term: Xhance
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
study doc: 
study doc: 
study doc: 
study doc: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 