<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/NCT03766542</url>
  </required_header>
  <id_info>
    <org_study_id>OSPAP study</org_study_id>
    <nct_id>NCT03766542</nct_id>
  </id_info>
  <brief_title>Continuous Positive Pressure Versus Bi-level in Overlap Syndrome</brief_title>
  <official_title>Optimal Positive Airway Pressure in Overlap Syndrome: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Sao Joao</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Marta Drummond MD PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Joao Carlos Winck MD PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mafalda van Zeller MD Phstud</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Sao Joao</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Continuous positive airway pressure (CPAP) became the established treatment for overlap&#xD;
      syndrome (OS). It has been showed that the survival benefits of CPAP favored hypercapnic&#xD;
      patients. When considering hypercapnic stable COPD patients, survival benefits occurred when&#xD;
      the use of bi- level ventilation therapy was targeted to significantly reduce hypercapnia.&#xD;
&#xD;
      This highlights the relevance of hypercapnia and hypoventilation correction. Thus, the&#xD;
      purpose of this study is to compare the use of CPAP to Bi-level ventilation in hypercapnic OS&#xD;
      patients, since the later may correct not only the airway patency but also increase the&#xD;
      magnitude of each breath.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD)&#xD;
      represent two of the most prevalent respiratory disorders in clinical practice and their&#xD;
      coexistence is often described has &quot;overlap syndrome&quot; (OS) In patients with COPD, the&#xD;
      coexistence of OSA is associated with an increased risk of death from any cause, and&#xD;
      hospitalization because of COPD exacerbation. Treatment with continuous positive airway&#xD;
      pressure (CPAP) has been showed to be effective and associated with improved survival and&#xD;
      decreased hospitalizations. When CPAP became established treatment for overlap syndrome, a&#xD;
      multivariate analysis revealed that the hours of CPAP use were an independent predictor of&#xD;
      mortality. Furthermore, it has been showed that the survival benefit of CPAP favors&#xD;
      hypercapnic patients with overlap syndrome.&#xD;
&#xD;
      Regarding hypercapnic stable COPD patients, the best results with long-term non-invasive&#xD;
      positive pressure ventilation have been noted in studies using more intensive strategies of&#xD;
      ventilation, with higher inspiratory pressures and higher backup rates that improved or even&#xD;
      normalized daytime hypercapnia. In fact, survival benefits occurred when ventilation was&#xD;
      targeted to significantly reduce hypercapnia.&#xD;
&#xD;
      As for typical COPD, overlap syndrome patients might also benefit from optimal daytime&#xD;
      hypercapnia correction, which could be better achieved using bi-level ventilation instead of&#xD;
      CPAP, since it could not only maintain airway patency but also improve alveolar ventilation.&#xD;
&#xD;
      This study aims to compare CPAP therapy to bi-level ventilatory support in overlap syndrome&#xD;
      patients, not only for the efficacy to achieve hypercapnia reduction, but also regarding&#xD;
      acute disease exacerbations, symptoms and treatment compliance. Therefore, the authors&#xD;
      designed a randomized controlled trial with recruitment and power calculations based on the&#xD;
      applicant's own data.&#xD;
&#xD;
      After the diagnosis, patients will be randomized either for CPAP or BPAP treatment.&#xD;
&#xD;
      If CPAP is to be initiated, optimal pressure to maintain upper airway patency will be&#xD;
      determined. If there are continued obstructive respiratory events at 15 cm H2O of CPAP,&#xD;
      patients will cross-over to the BPAP study arm.&#xD;
&#xD;
      Regarding BPAP titration, patients will be treated with ventilators set in pressure support&#xD;
      spontaneous/timed mode, both inspiratory and expiratory positive airway pressures (IPAP and&#xD;
      EPAP) will be manually titrated. EPAP will ensure optimal pressure for maintaining upper&#xD;
      airway patency and IPAP will be defined according to patient tolerance and pressure support&#xD;
      necessary to achieve normal PaCO2 values or to reduce baseline PaCO2 by 20% or more;&#xD;
      Follow-up will be performed at 1, 6 and 12 months. Follow-up will include clinical evaluation&#xD;
      with physical examination and questionnaires (COPD Assessment test, Epworth Sleepiness Scale&#xD;
      and MRC dyspnea score), blood gas analysis, treatment adherence, AHI, nocturnal pulse&#xD;
      oximetry and exacerbations.&#xD;
&#xD;
      12-month follow-up will also include lung function test, 6-min walking test and nocturnal&#xD;
      capnography.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 1, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective randomized controlled trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>diurnal hypercapnia (pCO2 &lt;= 45 mmH2O )</measure>
    <time_frame>1 year</time_frame>
    <description>(PaCO2 &lt;= 45 mmH2O )</description>
  </primary_outcome>
  <primary_outcome>
    <measure>nocturnal oxygen desaturation correction</measure>
    <time_frame>1 year</time_frame>
    <description>Mean nocturnal SpO2 &gt;=90%, with &lt;10% of the total recording time &lt;90% after correction of leaks)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in FEV1</measure>
    <time_frame>1 year</time_frame>
    <description>Forced Expiratory Volume (FEV1) in first second (% of predicted) from pre-intervention to follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in FVC</measure>
    <time_frame>1 year</time_frame>
    <description>Forced vital capacity (FVC) (% of predicted) from pre-intervention to follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in RV</measure>
    <time_frame>1 year</time_frame>
    <description>Residual volume (RV) (% of predicted) from pre-intervention to follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>exercise tolerance</measure>
    <time_frame>1 year</time_frame>
    <description>Change in the 6 minute walking test from pre-intervention to follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleepiness evaluation</measure>
    <time_frame>1 year</time_frame>
    <description>Epworth sleepiness scale is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.&#xD;
Comparation of patient score from pre-intervention to follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>acute respiratory exacerbations</measure>
    <time_frame>1 year</time_frame>
    <description>Frequency of acute exacerbations of COPD requiring addition of antibiotics and or steroids and or hospital admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance to PAP</measure>
    <time_frame>1 year</time_frame>
    <description>median hours of compliance per night</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PAP usage</measure>
    <time_frame>1 year</time_frame>
    <description>percentage of days of use per month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspnoea evaluation</measure>
    <time_frame>1 year</time_frame>
    <description>The mMRC Dyspnea Scale quantifies disability attributable to breathlessness and is useful for baseline dyspnea characterization in patients with respiratory diseases. The score can range from 0 to 4. The higher the mMRC score the higher the dyspnea.&#xD;
Comparation of patient score from pre-intervention to follow up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms of COPD</measure>
    <time_frame>1 year</time_frame>
    <description>COPD Assessment test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apneia/Hiponeia Index</measure>
    <time_frame>1 year</time_frame>
    <description>Number of Residual AHI/per hour</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nocturnal hypoventilation</measure>
    <time_frame>1 year</time_frame>
    <description>∆PtcCO2&lt;10mmHg during night from pre-intervention to follow up</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Overlap Syndrome</condition>
  <condition>Nocturnal Hypoventilation</condition>
  <arm_group>
    <arm_group_label>CPAP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oronasal CPAP therapy applied as per current international guidelines</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bi-level</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oronasal Bi-level therapy + supplemental oxygen (if necessary) applied as per current international guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bi-level positive airway pressure with ventilatory support</intervention_name>
    <description>Positive airway pressure will be applied in the experimental group through a oronasal interface, in ventilatory support mode (Bi-level) with a fixed backup rate.</description>
    <arm_group_label>Bi-level</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>continuous positive airway pressure without ventilatory support</intervention_name>
    <description>Continuous positive airway pressure (CPAP) will be applied in the active comparator group through a oronasal interface.</description>
    <arm_group_label>CPAP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD (FEV1/FVC &lt; 70 (post-BD) and history of smoking - 10 PPY)&#xD;
&#xD;
          -  FEV1&lt; 80% and COPD symptoms&#xD;
&#xD;
          -  AHI ≥ 15 events/hour&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Persistent hypercapnic respiratory failure with acidosis (defined as pH &lt;7.30 after&#xD;
             bronchodilators)&#xD;
&#xD;
          -  Hypoxia requiring long term oxygen therapy&#xD;
&#xD;
          -  BMI &gt; 35 kg/m2&#xD;
&#xD;
          -  Previously-initiated long term non-invasive positive pressure ventilation&#xD;
&#xD;
          -  Other lung disease resulting in respiratory symptoms&#xD;
&#xD;
          -  Age &lt;40 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Malignant comorbidities&#xD;
&#xD;
          -  Patients undergoing renal replacement therapy&#xD;
&#xD;
          -  Restrictive lung disease causing hypercapnia&#xD;
&#xD;
          -  Severe heart failure, unstable angina and severe arrhythmias&#xD;
&#xD;
          -  Inability to comply with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>February 8, 2017</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>December 5, 2018</last_update_submitted>
  <last_update_submitted_qc>December 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Sao Joao</investigator_affiliation>
    <investigator_full_name>Miguel R. Goncalves</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoventilation</mesh_term>
    <mesh_term>Undifferentiated Connective Tissue Diseases</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03766542
org study id: OSPAP study
nct id: NCT03766542
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Continuous positive airway pressure (CPAP) became the established treatment for overlap
      syndrome (OS). It has been showed that the survival benefits of CPAP favored hypercapnic
      patients. When considering hypercapnic stable COPD patients, survival benefits occurred when
      the use of bi- level ventilation therapy was targeted to significantly reduce hypercapnia.

      This highlights the relevance of hypercapnia and hypoventilation correction. Thus, the
      purpose of this study is to compare the use of CPAP to Bi-level ventilation in hypercapnic OS
      patients, since the later may correct not only the airway patency but also increase the
      magnitude of each breath.
Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD)
      represent two of the most prevalent respiratory disorders in clinical practice and their
      coexistence is often described has "overlap syndrome" (OS) In patients with COPD, the
      coexistence of OSA is associated with an increased risk of death from any cause, and
      hospitalization because of COPD exacerbation. Treatment with continuous positive airway
      pressure (CPAP) has been showed to be effective and associated with improved survival and
      decreased hospitalizations. When CPAP became established treatment for overlap syndrome, a
      multivariate analysis revealed that the hours of CPAP use were an independent predictor of
      mortality. Furthermore, it has been showed that the survival benefit of CPAP favors
      hypercapnic patients with overlap syndrome.

      Regarding hypercapnic stable COPD patients, the best results with long-term non-invasive
      positive pressure ventilation have been noted in studies using more intensive strategies of
      ventilation, with higher inspiratory pressures and higher backup rates that improved or even
      normalized daytime hypercapnia. In fact, survival benefits occurred when ventilation was
      targeted to significantly reduce hypercapnia.

      As for typical COPD, overlap syndrome patients might also benefit from optimal daytime
      hypercapnia correction, which could be better achieved using bi-level ventilation instead of
      CPAP, since it could not only maintain airway patency but also improve alveolar ventilation.

      This study aims to compare CPAP therapy to bi-level ventilatory support in overlap syndrome
      patients, not only for the efficacy to achieve hypercapnia reduction, but also regarding
      acute disease exacerbations, symptoms and treatment compliance. Therefore, the authors
      designed a randomized controlled trial with recruitment and power calculations based on the
      applicant's own data.

      After the diagnosis, patients will be randomized either for CPAP or BPAP treatment.

      If CPAP is to be initiated, optimal pressure to maintain upper airway patency will be
      determined. If there are continued obstructive respiratory events at 15 cm H2O of CPAP,
      patients will cross-over to the BPAP study arm.

      Regarding BPAP titration, patients will be treated with ventilators set in pressure support
      spontaneous/timed mode, both inspiratory and expiratory positive airway pressures (IPAP and
      EPAP) will be manually titrated. EPAP will ensure optimal pressure for maintaining upper
      airway patency and IPAP will be defined according to patient tolerance and pressure support
      necessary to achieve normal PaCO2 values or to reduce baseline PaCO2 by 20% or more;
      Follow-up will be performed at 1, 6 and 12 months. Follow-up will include clinical evaluation
      with physical examination and questionnaires (COPD Assessment test, Epworth Sleepiness Scale
      and MRC dyspnea score), blood gas analysis, treatment adherence, AHI, nocturnal pulse
      oximetry and exacerbations.

      12-month follow-up will also include lung function test, 6-min walking test and nocturnal
      capnography.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective randomized controlled trial.
primary purpose: Treatment
masking: None (Open Label)
measure: diurnal hypercapnia (pCO2 <= 45 mmH2O )
time frame: 1 year
description: (PaCO2 <= 45 mmH2O )
measure: nocturnal oxygen desaturation correction
time frame: 1 year
description: Mean nocturnal SpO2 >=90%, with <10% of the total recording time <90% after correction of leaks)
measure: Changes in FEV1
time frame: 1 year
description: Forced Expiratory Volume (FEV1) in first second (% of predicted) from pre-intervention to follow up
measure: Changes in FVC
time frame: 1 year
description: Forced vital capacity (FVC) (% of predicted) from pre-intervention to follow up
measure: Changes in RV
time frame: 1 year
description: Residual volume (RV) (% of predicted) from pre-intervention to follow up
measure: exercise tolerance
time frame: 1 year
description: Change in the 6 minute walking test from pre-intervention to follow up
measure: Sleepiness evaluation
time frame: 1 year
description: Epworth sleepiness scale is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.
Comparation of patient score from pre-intervention to follow up
measure: acute respiratory exacerbations
time frame: 1 year
description: Frequency of acute exacerbations of COPD requiring addition of antibiotics and or steroids and or hospital admission
measure: Compliance to PAP
time frame: 1 year
description: median hours of compliance per night
measure: PAP usage
time frame: 1 year
description: percentage of days of use per month
measure: Dyspnoea evaluation
time frame: 1 year
description: The mMRC Dyspnea Scale quantifies disability attributable to breathlessness and is useful for baseline dyspnea characterization in patients with respiratory diseases. The score can range from 0 to 4. The higher the mMRC score the higher the dyspnea.
Comparation of patient score from pre-intervention to follow up
measure: Symptoms of COPD
time frame: 1 year
description: COPD Assessment test
measure: Apneia/Hiponeia Index
time frame: 1 year
description: Number of Residual AHI/per hour
measure: nocturnal hypoventilation
time frame: 1 year
description: ∆PtcCO2<10mmHg during night from pre-intervention to follow up
arm group label: CPAP
arm group type: Active Comparator
description: Oronasal CPAP therapy applied as per current international guidelines
arm group label: Bi-level
arm group type: Experimental
description: Oronasal Bi-level therapy + supplemental oxygen (if necessary) applied as per current international guidelines
intervention type: Device
intervention name: Bi-level positive airway pressure with ventilatory support
description: Positive airway pressure will be applied in the experimental group through a oronasal interface, in ventilatory support mode (Bi-level) with a fixed backup rate.
arm group label: Bi-level
intervention type: Device
intervention name: continuous positive airway pressure without ventilatory support
description: Continuous positive airway pressure (CPAP) will be applied in the active comparator group through a oronasal interface.
arm group label: CPAP
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Hospital Sao Joao
investigator full name: Miguel R. Goncalves
investigator title: Clinical Professor
mesh term: Hypoventilation
mesh term: Undifferentiated Connective Tissue Diseases
mesh term: Syndrome
sharing ipd: Undecided