<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/NCT04413643</url>
  </required_header>
  <id_info>
    <org_study_id>18-25750</org_study_id>
    <nct_id>NCT04413643</nct_id>
  </id_info>
  <brief_title>NIV for COPD: Hospital to Home</brief_title>
  <acronym>H2H</acronym>
  <official_title>Noninvasive Ventilation for Chronic Obstructive Pulmonary Disease: Hospital to Home Pilot</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>San Francisco Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ResMed</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>San Francisco Veterans Affairs Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to evaluate the impact of providing patients admitted with acute&#xD;
      exacerbations of COPD (AECOPD) with non-invasive ventilation (NIV)home devices prior to&#xD;
      discharge on hospital readmission rates and other secondary outcomes.&#xD;
&#xD;
      Aim 1 To test whether continuation of NIV at home after being initiated during&#xD;
      hospitalization for AECOPD improves subsequent admission-free survival in patients with&#xD;
      chronic hypercapnic respiratory failure secondary to COPD&#xD;
&#xD;
      Hypothesis 1: The use of targeted NIV during hospitalization with continuation upon discharge&#xD;
      to home will improve one-year all-cause mortality as compared to published mortality in the&#xD;
      current literature.&#xD;
&#xD;
      Hypothesis 2: The use of targeted NIV during hospitalization with continuation upon discharge&#xD;
      to home will reduce readmission rates for AECOPD within-institution historical data.&#xD;
&#xD;
      Aim 2 To evaluate the feasibility of a larger multisite randomized controlled trial in&#xD;
      veterans using inclusion and exclusion criteria specified in this pilot.&#xD;
&#xD;
      Outcomes&#xD;
&#xD;
      Primary: Event-free survival (re-hospitalization for AECOPD, time to readmission for AECOPD,&#xD;
      and all-cause mortality)&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        1. Unplanned readmission rates (all complications)&#xD;
&#xD;
        2. Time to readmissions for admissions other than AECOPD.&#xD;
&#xD;
        3. Arterial blood gas/Venous blood gas (ABG/VBG): PaO2, PaCO2 and serum bicarbonate at&#xD;
           Baseline, 6 and 12 months&#xD;
&#xD;
        4. Pulmonary function (handheld spirometer or in-laboratory based on specific institution&#xD;
           resources) at Baseline, 6, and 12 months 5.6 minute walk test at Baseline, 6,and 12&#xD;
           months&#xD;
&#xD;
      6.Health related quality of life (HRQOL) measured by the St. Georges respiratory&#xD;
      questionnaires (SGRQ) at Baseline, 1,3,6,9 and 12 months 7.Adherence to NIV at Week 1-2,&#xD;
      Months 1,3,6,9 and 12 8.Sleep assessed by type 3 portable monitors 9.Sleep assessed by&#xD;
      questionnaires: Insomnia severity index (ISI), Epworth Sleepiness Scale (ESS), Pittsburgh&#xD;
      Sleep Quality Index (PSQI), Functional Outcomes of Sleep Short Form (FOSQ-10) at Baseline,&#xD;
      1,3,6,9 and 12 months 11.Utilization of healthcare services (number of visits to outpatient&#xD;
      clinics and emergency services, number of inpatient admissions)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality&#xD;
      worldwide, with the economic and social burden of disease anticipated to increase annually.&#xD;
      Acute exacerbations of COPD (AECOPD) are associated with significant in-hospital mortality&#xD;
      (6-8%), high readmission rates (60-80%), and even more dramatic 1-year mortality (23-49%).&#xD;
&#xD;
      The use of non-invasive ventilation (NIV) has been extensively evaluated in both patients&#xD;
      with stable disease in the home setting and in AECOPD during hospitalization. It is widely&#xD;
      accepted that NIV used during AECOPD in the inpatient setting reduces rates of endotracheal&#xD;
      intubation, as well as length of ICU and hospital stay. Long-term use of NIV, particularly at&#xD;
      higher pressures, in the home setting in COPD patients with evidence of chronic compensated&#xD;
      respiratory acidosis (PaCO2 &gt;45mmHg) decreases elevated PaCo2 and serum bicarbonate levels,&#xD;
      improves pulmonary function, and improves quality of life. Little is known about whether&#xD;
      patients initiated on NIV during an AECOPD and subsequently transitioned to long-term home&#xD;
      NIV on discharge demonstrate reduced AECOPD rates, readmission rates, or differences in&#xD;
      morbidity and mortality. The few existing randomized trials aimed at this patient population&#xD;
      suffer from criticisms of lack of power, varying degrees of patient symptoms, conflicting&#xD;
      results, and inconsistent approaches in NIV strategies. Nonetheless, this is an important&#xD;
      population to address, as AECOPD frequently leads to accelerated loss of lung function&#xD;
      (pre-AECOPD function not recovered), decreased quality of life (QOL), more frequent&#xD;
      exacerbations, and higher overall mortality. If NIV can minimize the loss of lung function&#xD;
      during the transition period following AECOPD, QOL, physical activity tolerance, readmission&#xD;
      rates and overall mortality may improve.&#xD;
&#xD;
      Economic analyses of the use of NIV in patients with AECOPD transitioning from the inpatient&#xD;
      to home setting are also sparse, but of high value as healthcare transitions toward bundled&#xD;
      payments and penalties for readmissions. This pilot study seeks to better inform the&#xD;
      literature on the role of NIV initiated during inpatient AECOPD and continued long-term&#xD;
      following discharge home in patients with chronic hypercapnic respiratory failure due to&#xD;
      COPD. The investigators hypothesize that the use of NIV during acute inpatient treatment of&#xD;
      AECOPD followed by continuation of NIV therapy long-term at home will improve admission free&#xD;
      survival, improve quality of life, reduce 1-year exacerbation rates, and reduce 30d&#xD;
      readmissions.&#xD;
&#xD;
      This is a prospective 1-year interventional pilot study that will occur at 4 Veterans Affairs&#xD;
      (VA) hospitals (Sacramento, Durham, Pittsburgh, and San Francisco).&#xD;
&#xD;
      The total enrollment goal across all sites is 50. Total study period expected includes an&#xD;
      enrollment period of approximately 10-12 months and follow-up period of 12 months for a total&#xD;
      study duration of approximately 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a feasibility trial intended to inform a larger clinical trial based on outcomes data collected.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>1 year</time_frame>
    <description>Re-hospitalization for AECOPD, time to readmission for AECOPD, and all-cause mortality</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Unplanned readmission rates (all complications)</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to readmissions for admissions other than AECOPD</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PaO2 levels from baseline to 12mo</measure>
    <time_frame>1 year</time_frame>
    <description>PaO2 will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change PaCO2 levels from baseline to 12mo</measure>
    <time_frame>1 year</time_frame>
    <description>PaCO2 will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum bicarbonate levels from baseline to 12mo</measure>
    <time_frame>1 year</time_frame>
    <description>Serum bicarbonate will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Forced expiratory volume (FEV1) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Absolute Forced Expiratory Volume (L) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>% Forced Expiratory Volume measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Forced Vital Capacity (FVC) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Absolute Forced Vital Capacity (L) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>% Forced Vital Capacity measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Total Lung Capacity (TLC) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Absolute Total Lung Capacity (L) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>% Total Lung Capacity measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Residual Volume (RV) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Absolute Residual Volume (L) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>% Residual Volume measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>FEV1/FVC% measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spirometry/Lung Function</measure>
    <time_frame>1 year</time_frame>
    <description>Diffusion Capacity (DLCO) measured at baseline, 6mo and 12mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 minute walk test</measure>
    <time_frame>1 year</time_frame>
    <description>At baseline, 6 mo and 12 mo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>St. Georges Respiratory Questionnaire</measure>
    <time_frame>1 year</time_frame>
    <description>50-item, 3 component questionnaire. Scores range from 0-100 with a higher score indicating more limitations. Measures the impact of breathing symptoms on quality of life. Administered at baseline, 1, 3, 6, 9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence/Compliance with NIV</measure>
    <time_frame>1 year</time_frame>
    <description>Standard total days used since therapy initiation (day 0). Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence/Compliance with NIV</measure>
    <time_frame>1 year</time_frame>
    <description>Percent days with use &gt;4h/d. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence/Compliance with NIV</measure>
    <time_frame>1 year</time_frame>
    <description>Average time used on days used. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence/Compliance with NIV</measure>
    <time_frame>1 year</time_frame>
    <description>Average time used on all days. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep assessed by type 3 portable monitors and transcutaneous capnography</measure>
    <time_frame>1 year</time_frame>
    <description>At baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epworth Sleepiness Scale assessment for daytime sleepiness</measure>
    <time_frame>1 year</time_frame>
    <description>8 question survey that measures the propensity of falling asleep in different situations. Composite score reported, with a range from 0-24, the higher the score indicating a greater propensity for falling asleep. Administered at baseline, 1, 3, 6, 9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insomnia Severity Index assessment for difficulty falling asleep and staying asleep.</measure>
    <time_frame>1 year</time_frame>
    <description>7-item survey that uses a likert scale. Measures the nature, severity, and impact of insomnia in adults. Composite score reported (0-28), with a higher score indicating a greater severity of insomnia. Administered at baseline, 1, 3, 6, 9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh sleep quality index (PSQI) questionnaire to measure sleep disturbance and sleep habits</measure>
    <time_frame>1 year</time_frame>
    <description>19 item questionnaire with 7 domains (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction), using a likert scale. Measures sleep disturbance and usual sleep habits during the prior month only. A global socre of 0-21 is used, with a score &gt;5 indicating poor sleep quality. The higher the score the poorer the sleep quality. Administered at baseline, 1, 3, 6, 9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Outcomes of Sleep Questionnaire (short form) to measure functional status resulting from sleepiness and is a measure of sleep-related HRQoL.</measure>
    <time_frame>1 year</time_frame>
    <description>10 item questionnaire with 5 subscales. Subscale scores are averaged to obtain a total score ranging from 5-20, with a higher score indicating better functional status. Administered at baseline, 1, 3, 6, 9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Utilization of healthcare services (visits to outpatient clinics and emergency services, and number of inpatient admissions)</measure>
    <time_frame>1 year</time_frame>
    <description>Visits (both outpatient and inpatient) will be identified based on VA-specific stop codes which define what type of visit occurred (specialty, date, and provider type).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <condition>Noninvasive Ventilation</condition>
  <arm_group>
    <arm_group_label>Noninvasive Ventilation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be introduced to NIV and educated on sleep disordered breathing. NIV will be initiated during hospitalization following resolution of acute respiratory failure. NIV settings will be based on inspiratory and expiratory positive airway pressures (IPAP, EPAP), rates, and tidal volumes tolerated during the acute phase of treatment. Initial settings will be set with goals of tolerance and acceptance of therapy. Minimum pressure difference between IPAP and EPAP settings will be 5cmH20. Volume assured pressure support mode with a target tidal volume (Vt) of 8ml/kg ideal body weight will be used. Final device settings and patient parameters will be documented after 10 minutes of acclimation to the device. Data from the device will be reviewed the following day. Tolerance, mask comfort, and acceptance of therapy will be assessed. Changes to settings, mask interface, or other comfort features will be performed at this initial reassessment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Noninvasive Ventilation</intervention_name>
    <description>The use of non-invasive ventilation (NIV) has been extensively evaluated in both patients with stable disease in the home setting and in AECOPD during hospitalization. It is widely accepted that NIV used during AECOPD in the inpatient setting reduces rates of endotracheal intubation, as well as length of ICU and hospital stay. Long-term use of NIV, particularly at higher pressures, in the home setting in COPD patients with evidence of chronic compensated respiratory acidosis (PaCO2 &gt;45mmHg) decreases elevated PaCo2 and serum bicarbonate levels, improves pulmonary function, and improves quality of life. Little is known about whether patients initiated on NIV during an AECOPD and subsequently transitioned to long-term home NIV on discharge demonstrate reduced AECOPD rates, readmission rates, or differences in morbidity and mortality.</description>
    <arm_group_label>Noninvasive Ventilation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Admission for acute hypercapnic respiratory failure requiring mechanical ventilation&#xD;
             or NIV&#xD;
&#xD;
          2. Resolution of acute respiratory failure reflected by normalization of pH and downgrade&#xD;
             of clinical status to ward or floor status.&#xD;
&#xD;
          3. Severe COPD defined by GOLD stage 3 (FEV1 30-50%) or 4 (FEV1 &lt; 30%) OR GOLD C or D.&#xD;
             Pulmonary function tests (PFTs) done within 3 years preceding admission are acceptable&#xD;
             to document an obstructive ventilatory defect and decrease diffusion capacity&#xD;
             consistent with emphysema and COPD. If no PFTs are available, bedside spirometry will&#xD;
             be performed to confirm COPD.&#xD;
&#xD;
          4. Chronic compensated respiratory acidosis based on PaCO2 &gt;52 adjusted for pH 7.40, on&#xD;
             pre-admission laboratory values or after resolution of acute respiratory failure.&#xD;
&#xD;
          5. Able to consent without surrogate and complete all required study visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Moderate or severe obstructive sleep apnea (OSA), apnea-hypopnea index (AHI) &gt;15/h.&#xD;
             Sleep testing done within the prior 3 years with no increase in body mass index (BMI)&#xD;
             &gt;2kg/m2 or major change in cardiopulmonary conditions (new reduced ejection heart&#xD;
             failure [HFrEF], atrial fibrillation [AFib], opioid use with morphine dose equivalent&#xD;
             (MDDE) &gt;120mg, or cardiothoracic surgery for lung resection or coronary artery bypass&#xD;
             grafting) will be accepted for AHI severity.&#xD;
&#xD;
          2. BMI&gt;35 kg/m2&#xD;
&#xD;
          3. Congestive heart failure (HFrEF, EF&lt; 45%)&#xD;
&#xD;
          4. Other cause of chronic respiratory failure: Obesity hypoventilation syndrome, spinal&#xD;
             cord injury (cervical or thoracic) neuromuscular disease, diaphragmatic paralysis,&#xD;
             chest wall restrictive ventilatory defect&#xD;
&#xD;
          5. Lack of stable housing, homelessness, or unreliable electricity source in home&#xD;
             environment.&#xD;
&#xD;
          6. Use of NIV at home within past three months&#xD;
&#xD;
          7. Failure to tolerate NIV during initial hospitalization&#xD;
&#xD;
          8. Unable or unwilling to comply with the protocol&#xD;
&#xD;
          9. Age &lt;18 years&#xD;
&#xD;
         10. Inability to consent due to limited cognitive capacity&#xD;
&#xD;
         11. Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathleen Sarmiento, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>San Francisco VA Health Care System</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Julia von Oppenfeld, BA</last_name>
    <phone>415-221-4810</phone>
    <phone_ext>23482</phone_ext>
    <email>Julia.vonOppenfeld@va.gov</email>
  </overall_contact>
  <location>
    <facility>
      <name>San Francisco VA Health Care System</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94121</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Julia von Oppenfeld, BA</last_name>
    </contact>
    <investigator>
      <last_name>Kathleen Sarmiento, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mehrdad Arjomandi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, Dowson L, Duffy N, Gibson GJ, Hughes PD, Hurst JR, Lewis KE, Mukherjee R, Nickol A, Oscroft N, Patout M, Pepperell J, Smith I, Stradling JR, Wedzicha JA, Polkey MI, Elliott MW, Hart N. Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial. JAMA. 2017 Jun 6;317(21):2177-2186. doi: 10.1001/jama.2017.4451.</citation>
    <PMID>28528348</PMID>
  </reference>
  <reference>
    <citation>Budweiser S, Hitzl AP, Jorres RA, Heinemann F, Arzt M, Schroll S, Pfeifer M. Impact of noninvasive home ventilation on long-term survival in chronic hypercapnic COPD: a prospective observational study. Int J Clin Pract. 2007 Sep;61(9):1516-22. doi: 10.1111/j.1742-1241.2007.01427.x.</citation>
    <PMID>17686094</PMID>
  </reference>
  <reference>
    <citation>De Backer L, Vos W, Dieriks B, Daems D, Verhulst S, Vinchurkar S, Ides K, De Backer J, Germonpre P, De Backer W. The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study. Int J Chron Obstruct Pulmon Dis. 2011;6:615-24. doi: 10.2147/COPD.S22823. Epub 2011 Nov 18.</citation>
    <PMID>22135493</PMID>
  </reference>
  <reference>
    <citation>Storre JH, Matrosovich E, Ekkernkamp E, Walker DJ, Schmoor C, Dreher M, Windisch W. Home mechanical ventilation for COPD: high-intensity versus target volume noninvasive ventilation. Respir Care. 2014 Sep;59(9):1389-97. doi: 10.4187/respcare.02941. Epub 2014 Jul 29.</citation>
    <PMID>25074944</PMID>
  </reference>
  <reference>
    <citation>Oscroft NS, Chadwick R, Davies MG, Quinnell TG, Smith IE. Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD. Respir Med. 2014 Oct;108(10):1508-15. doi: 10.1016/j.rmed.2014.07.010. Epub 2014 Jul 23.</citation>
    <PMID>25123526</PMID>
  </reference>
  <reference>
    <citation>Mansfield D, Naughton MT. Effects of continuous positive airway pressure on lung function in patients with chronic obstructive pulmonary disease and sleep disordered breathing. Respirology. 1999 Dec;4(4):365-70. doi: 10.1046/j.1440-1843.1999.00206.x.</citation>
    <PMID>10612570</PMID>
  </reference>
  <reference>
    <citation>Gunduz C, Basoglu OK, Tasbakan MS. Prevalence of overlap syndrome in chronic obstructive pulmonary disease patients without sleep apnea symptoms. Clin Respir J. 2018 Jan;12(1):105-112. doi: 10.1111/crj.12493. Epub 2016 Jun 6.</citation>
    <PMID>27148977</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>October 7, 2019</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>May 28, 2020</last_update_submitted>
  <last_update_submitted_qc>May 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>San Francisco Veterans Affairs Medical Center</investigator_affiliation>
    <investigator_full_name>Kathleen Sarmiento</investigator_full_name>
    <investigator_title>Staff Physician, Medicine Service</investigator_title>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>BIPAP</keyword>
  <keyword>NIV</keyword>
  <keyword>Respiratory failure</keyword>
  <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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04413643
org study id: 18-25750
nct id: NCT04413643
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This is a pilot study to evaluate the impact of providing patients admitted with acute
      exacerbations of COPD (AECOPD) with non-invasive ventilation (NIV)home devices prior to
      discharge on hospital readmission rates and other secondary outcomes.

      Aim 1 To test whether continuation of NIV at home after being initiated during
      hospitalization for AECOPD improves subsequent admission-free survival in patients with
      chronic hypercapnic respiratory failure secondary to COPD

      Hypothesis 1: The use of targeted NIV during hospitalization with continuation upon discharge
      to home will improve one-year all-cause mortality as compared to published mortality in the
      current literature.

      Hypothesis 2: The use of targeted NIV during hospitalization with continuation upon discharge
      to home will reduce readmission rates for AECOPD within-institution historical data.

      Aim 2 To evaluate the feasibility of a larger multisite randomized controlled trial in
      veterans using inclusion and exclusion criteria specified in this pilot.

      Outcomes

      Primary: Event-free survival (re-hospitalization for AECOPD, time to readmission for AECOPD,
      and all-cause mortality)

      Secondary:

        1. Unplanned readmission rates (all complications)

        2. Time to readmissions for admissions other than AECOPD.

        3. Arterial blood gas/Venous blood gas (ABG/VBG): PaO2, PaCO2 and serum bicarbonate at
           Baseline, 6 and 12 months

        4. Pulmonary function (handheld spirometer or in-laboratory based on specific institution
           resources) at Baseline, 6, and 12 months 5.6 minute walk test at Baseline, 6,and 12
           months

      6.Health related quality of life (HRQOL) measured by the St. Georges respiratory
      questionnaires (SGRQ) at Baseline, 1,3,6,9 and 12 months 7.Adherence to NIV at Week 1-2,
      Months 1,3,6,9 and 12 8.Sleep assessed by type 3 portable monitors 9.Sleep assessed by
      questionnaires: Insomnia severity index (ISI), Epworth Sleepiness Scale (ESS), Pittsburgh
      Sleep Quality Index (PSQI), Functional Outcomes of Sleep Short Form (FOSQ-10) at Baseline,
      1,3,6,9 and 12 months 11.Utilization of healthcare services (number of visits to outpatient
      clinics and emergency services, number of inpatient admissions)
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality
      worldwide, with the economic and social burden of disease anticipated to increase annually.
      Acute exacerbations of COPD (AECOPD) are associated with significant in-hospital mortality
      (6-8%), high readmission rates (60-80%), and even more dramatic 1-year mortality (23-49%).

      The use of non-invasive ventilation (NIV) has been extensively evaluated in both patients
      with stable disease in the home setting and in AECOPD during hospitalization. It is widely
      accepted that NIV used during AECOPD in the inpatient setting reduces rates of endotracheal
      intubation, as well as length of ICU and hospital stay. Long-term use of NIV, particularly at
      higher pressures, in the home setting in COPD patients with evidence of chronic compensated
      respiratory acidosis (PaCO2 >45mmHg) decreases elevated PaCo2 and serum bicarbonate levels,
      improves pulmonary function, and improves quality of life. Little is known about whether
      patients initiated on NIV during an AECOPD and subsequently transitioned to long-term home
      NIV on discharge demonstrate reduced AECOPD rates, readmission rates, or differences in
      morbidity and mortality. The few existing randomized trials aimed at this patient population
      suffer from criticisms of lack of power, varying degrees of patient symptoms, conflicting
      results, and inconsistent approaches in NIV strategies. Nonetheless, this is an important
      population to address, as AECOPD frequently leads to accelerated loss of lung function
      (pre-AECOPD function not recovered), decreased quality of life (QOL), more frequent
      exacerbations, and higher overall mortality. If NIV can minimize the loss of lung function
      during the transition period following AECOPD, QOL, physical activity tolerance, readmission
      rates and overall mortality may improve.

      Economic analyses of the use of NIV in patients with AECOPD transitioning from the inpatient
      to home setting are also sparse, but of high value as healthcare transitions toward bundled
      payments and penalties for readmissions. This pilot study seeks to better inform the
      literature on the role of NIV initiated during inpatient AECOPD and continued long-term
      following discharge home in patients with chronic hypercapnic respiratory failure due to
      COPD. The investigators hypothesize that the use of NIV during acute inpatient treatment of
      AECOPD followed by continuation of NIV therapy long-term at home will improve admission free
      survival, improve quality of life, reduce 1-year exacerbation rates, and reduce 30d
      readmissions.

      This is a prospective 1-year interventional pilot study that will occur at 4 Veterans Affairs
      (VA) hospitals (Sacramento, Durham, Pittsburgh, and San Francisco).

      The total enrollment goal across all sites is 50. Total study period expected includes an
      enrollment period of approximately 10-12 months and follow-up period of 12 months for a total
      study duration of approximately 2 years.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a feasibility trial intended to inform a larger clinical trial based on outcomes data collected.
primary purpose: Treatment
masking: None (Open Label)
measure: Event-free survival
time frame: 1 year
description: Re-hospitalization for AECOPD, time to readmission for AECOPD, and all-cause mortality
measure: Unplanned readmission rates (all complications)
time frame: 1 year
measure: Time to readmissions for admissions other than AECOPD
time frame: 1 year
measure: Change in PaO2 levels from baseline to 12mo
time frame: 1 year
description: PaO2 will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate)
measure: Change PaCO2 levels from baseline to 12mo
time frame: 1 year
description: PaCO2 will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate)
measure: Change in serum bicarbonate levels from baseline to 12mo
time frame: 1 year
description: Serum bicarbonate will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate)
measure: Spirometry/Lung Function
time frame: 1 year
description: Forced expiratory volume (FEV1) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Absolute Forced Expiratory Volume (L) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: % Forced Expiratory Volume measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Forced Vital Capacity (FVC) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Absolute Forced Vital Capacity (L) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: % Forced Vital Capacity measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Total Lung Capacity (TLC) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Absolute Total Lung Capacity (L) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: % Total Lung Capacity measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Residual Volume (RV) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Absolute Residual Volume (L) measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: % Residual Volume measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: FEV1/FVC% measured at baseline, 6mo and 12mo
measure: Spirometry/Lung Function
time frame: 1 year
description: Diffusion Capacity (DLCO) measured at baseline, 6mo and 12mo
measure: 6 minute walk test
time frame: 1 year
description: At baseline, 6 mo and 12 mo
measure: St. Georges Respiratory Questionnaire
time frame: 1 year
description: 50-item, 3 component questionnaire. Scores range from 0-100 with a higher score indicating more limitations. Measures the impact of breathing symptoms on quality of life. Administered at baseline, 1, 3, 6, 9 and 12 months
measure: Adherence/Compliance with NIV
time frame: 1 year
description: Standard total days used since therapy initiation (day 0). Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.
measure: Adherence/Compliance with NIV
time frame: 1 year
description: Percent days with use >4h/d. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.
measure: Adherence/Compliance with NIV
time frame: 1 year
description: Average time used on days used. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.
measure: Adherence/Compliance with NIV
time frame: 1 year
description: Average time used on all days. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device.
measure: Sleep assessed by type 3 portable monitors and transcutaneous capnography
time frame: 1 year
description: At baseline
measure: Epworth Sleepiness Scale assessment for daytime sleepiness
time frame: 1 year
description: 8 question survey that measures the propensity of falling asleep in different situations. Composite score reported, with a range from 0-24, the higher the score indicating a greater propensity for falling asleep. Administered at baseline, 1, 3, 6, 9 and 12 months
measure: Insomnia Severity Index assessment for difficulty falling asleep and staying asleep.
time frame: 1 year
description: 7-item survey that uses a likert scale. Measures the nature, severity, and impact of insomnia in adults. Composite score reported (0-28), with a higher score indicating a greater severity of insomnia. Administered at baseline, 1, 3, 6, 9 and 12 months
measure: Pittsburgh sleep quality index (PSQI) questionnaire to measure sleep disturbance and sleep habits
time frame: 1 year
description: 19 item questionnaire with 7 domains (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction), using a likert scale. Measures sleep disturbance and usual sleep habits during the prior month only. A global socre of 0-21 is used, with a score >5 indicating poor sleep quality. The higher the score the poorer the sleep quality. Administered at baseline, 1, 3, 6, 9 and 12 months
measure: Functional Outcomes of Sleep Questionnaire (short form) to measure functional status resulting from sleepiness and is a measure of sleep-related HRQoL.
time frame: 1 year
description: 10 item questionnaire with 5 subscales. Subscale scores are averaged to obtain a total score ranging from 5-20, with a higher score indicating better functional status. Administered at baseline, 1, 3, 6, 9 and 12 months
measure: Utilization of healthcare services (visits to outpatient clinics and emergency services, and number of inpatient admissions)
time frame: 1 year
description: Visits (both outpatient and inpatient) will be identified based on VA-specific stop codes which define what type of visit occurred (specialty, date, and provider type).
arm group label: Noninvasive Ventilation
arm group type: Experimental
description: Subjects will be introduced to NIV and educated on sleep disordered breathing. NIV will be initiated during hospitalization following resolution of acute respiratory failure. NIV settings will be based on inspiratory and expiratory positive airway pressures (IPAP, EPAP), rates, and tidal volumes tolerated during the acute phase of treatment. Initial settings will be set with goals of tolerance and acceptance of therapy. Minimum pressure difference between IPAP and EPAP settings will be 5cmH20. Volume assured pressure support mode with a target tidal volume (Vt) of 8ml/kg ideal body weight will be used. Final device settings and patient parameters will be documented after 10 minutes of acclimation to the device. Data from the device will be reviewed the following day. Tolerance, mask comfort, and acceptance of therapy will be assessed. Changes to settings, mask interface, or other comfort features will be performed at this initial reassessment period.
intervention type: Device
intervention name: Noninvasive Ventilation
description: The use of non-invasive ventilation (NIV) has been extensively evaluated in both patients with stable disease in the home setting and in AECOPD during hospitalization. It is widely accepted that NIV used during AECOPD in the inpatient setting reduces rates of endotracheal intubation, as well as length of ICU and hospital stay. Long-term use of NIV, particularly at higher pressures, in the home setting in COPD patients with evidence of chronic compensated respiratory acidosis (PaCO2 >45mmHg) decreases elevated PaCo2 and serum bicarbonate levels, improves pulmonary function, and improves quality of life. Little is known about whether patients initiated on NIV during an AECOPD and subsequently transitioned to long-term home NIV on discharge demonstrate reduced AECOPD rates, readmission rates, or differences in morbidity and mortality.
arm group label: Noninvasive Ventilation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kathleen Sarmiento, MD, MPH
role: Principal Investigator
affiliation: San Francisco VA Health Care System
last name: Julia von Oppenfeld, BA
phone: 415-221-4810
phone ext: 23482
email: Julia.vonOppenfeld@va.gov
facility: 
contact: 
investigator: 
investigator: 
country: United States
citation: Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, Dowson L, Duffy N, Gibson GJ, Hughes PD, Hurst JR, Lewis KE, Mukherjee R, Nickol A, Oscroft N, Patout M, Pepperell J, Smith I, Stradling JR, Wedzicha JA, Polkey MI, Elliott MW, Hart N. Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial. JAMA. 2017 Jun 6;317(21):2177-2186. doi: 10.1001/jama.2017.4451.
PMID: 28528348
citation: Budweiser S, Hitzl AP, Jorres RA, Heinemann F, Arzt M, Schroll S, Pfeifer M. Impact of noninvasive home ventilation on long-term survival in chronic hypercapnic COPD: a prospective observational study. Int J Clin Pract. 2007 Sep;61(9):1516-22. doi: 10.1111/j.1742-1241.2007.01427.x.
PMID: 17686094
citation: De Backer L, Vos W, Dieriks B, Daems D, Verhulst S, Vinchurkar S, Ides K, De Backer J, Germonpre P, De Backer W. The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study. Int J Chron Obstruct Pulmon Dis. 2011;6:615-24. doi: 10.2147/COPD.S22823. Epub 2011 Nov 18.
PMID: 22135493
citation: Storre JH, Matrosovich E, Ekkernkamp E, Walker DJ, Schmoor C, Dreher M, Windisch W. Home mechanical ventilation for COPD: high-intensity versus target volume noninvasive ventilation. Respir Care. 2014 Sep;59(9):1389-97. doi: 10.4187/respcare.02941. Epub 2014 Jul 29.
PMID: 25074944
citation: Oscroft NS, Chadwick R, Davies MG, Quinnell TG, Smith IE. Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD. Respir Med. 2014 Oct;108(10):1508-15. doi: 10.1016/j.rmed.2014.07.010. Epub 2014 Jul 23.
PMID: 25123526
citation: Mansfield D, Naughton MT. Effects of continuous positive airway pressure on lung function in patients with chronic obstructive pulmonary disease and sleep disordered breathing. Respirology. 1999 Dec;4(4):365-70. doi: 10.1046/j.1440-1843.1999.00206.x.
PMID: 10612570
citation: Gunduz C, Basoglu OK, Tasbakan MS. Prevalence of overlap syndrome in chronic obstructive pulmonary disease patients without sleep apnea symptoms. Clin Respir J. 2018 Jan;12(1):105-112. doi: 10.1111/crj.12493. Epub 2016 Jun 6.
PMID: 27148977
responsible party type: Principal Investigator
investigator affiliation: San Francisco Veterans Affairs Medical Center
investigator full name: Kathleen Sarmiento
investigator title: Staff Physician, Medicine Service
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No