<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/NCT03803358</url>
  </required_header>
  <id_info>
    <org_study_id>NIV-Training</org_study_id>
    <nct_id>NCT03803358</nct_id>
  </id_info>
  <brief_title>NIV-Training in Hypercapnic COPD Patients</brief_title>
  <official_title>The Effects of Non-invasive Ventilation During Cycle Exercise Within a 3-week Pulmonary Rehabilitation Program in COPD Patients With Chronic Hypercapnic Respiratory Failure - a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Schön Klinik Berchtesgadener Land</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Löwenstein Medical GmbH &amp; Co. KG</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bad Reichenhaller Forschungsanstalt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Schön Klinik Berchtesgadener Land</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>
      The aim of the study is to investigate the additional effects of the use of NIV during&#xD;
      exercise within a 3-week PR program on exercise capacity in COPD patients with chronic&#xD;
      hypercapnic respiratory failure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Scientific Background/ Rationale:&#xD;
&#xD;
      Quality of life and exercise tolerance are commonly reduced in people with chronic&#xD;
      obstructive pulmonary disease (COPD), especially in people with chronic hypercapnic&#xD;
      respiratory failure (CHRF). Endurance exercise training as part of a pulmonary rehabilitation&#xD;
      (PR) programme is an important treatment for people with COPD and has been shown to improve&#xD;
      quality of life, exercise tolerance and physical activity. However, individuals with CHRF may&#xD;
      have difficulties performing endurance exercise at an adequate training intensity to achieve&#xD;
      the desired physiological changes.&#xD;
&#xD;
      Non-invasive ventilation (NIV) is a method of providing breathing support using a ventilator&#xD;
      and is usually delivered via a full face mask. A recent study showed that during a single&#xD;
      exercise session in people with CHRF, NIV dramatically improves exercise tolerance and&#xD;
      reduces breathlessness. Consequently, NIV used over a complete exercise training program may&#xD;
      allow people with COPD and CHRF to exercise at a higher intensity to achieve greater&#xD;
      improvement in exercise tolerance, quality of life and physical activity. So far this has&#xD;
      only been tested in a small number of studies with small numbers of participants, and none&#xD;
      with CHRF. It is currently not known from literature whether the demonstrated benefits of NIV&#xD;
      during exercise training are clinically worthwhile or cost-effective.&#xD;
&#xD;
      Aims The aim of the study is to investigate the additional effects of the use of NIV during&#xD;
      exercise within a 3-week PR program on exercise capacity in COPD patients with chronic&#xD;
      hypercapnic respiratory failure.&#xD;
&#xD;
      Hypothesis It is assumed that a 3-week exercise training program with additional NIV, using&#xD;
      titrated pressures, reduces the work of breathing. With this, it is theorized, COPD patients&#xD;
      with CHRF are able to train for a longer duration and/ or with higher training intensities&#xD;
      over the course of the training program and may achieve better PR outcomes.&#xD;
&#xD;
      Primary Hypothesis:&#xD;
&#xD;
      H.0: COPD-Patients with CHRF have the same increase in exercise capacity (endurance cycle&#xD;
      time) when training with additional NIV as without NIV, during a 3-week PR program.&#xD;
&#xD;
      H.1: COPD-Patients with CHRF have a superior increase in exercise capacity (endurance cycle&#xD;
      time) when training with additional NIV as without NIV, during a 3-week PR program.&#xD;
&#xD;
      Main Objective To determine if NIV during exercise is a useful tool for increasing exercise&#xD;
      tolerance in hypercapnic patients, exercise tolerance (cycle endurance time) will be measured&#xD;
      without NIV at PR admission/ discharge&#xD;
&#xD;
      Materials and Method A total of 26 COPD patient (age: 40-80 years) in GOLD Stages IV&#xD;
      diagnosed with CHRF, already treated with nocturnal NIV and referred for a comprehensive PR&#xD;
      program will be recruited and randomized into two groups: 1) exercise with NIV during&#xD;
      exercise (nocturnal NIV will continue) and 2) control group - exercise without NIV during&#xD;
      exercise (nocturnal NIV will continue).&#xD;
&#xD;
      Initially, patients will perform a maximum cardiopulmonary test to determine the Peak Work&#xD;
      Rate (WRpeak). On a separate day, patients will perform a cycle endurance test (CET) at&#xD;
      75%WRpeak without NIV using oxygen as prescribed, if needed. TcPCO2, heart rate and SpO2 via&#xD;
      SenTec will be measured continuously during CET. In addition to the continuously recorded&#xD;
      data, dyspnoea/ respiratory effort/ leg-fatigue (10-point Borg scale), capillary blood gases&#xD;
      and the arterial blood pressure will be taken at the beginning/ end/ recovery/ isotime of the&#xD;
      CET.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Actual">July 27, 2021</completion_date>
  <primary_completion_date type="Actual">July 27, 2021</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>A total of 26 COPD patients in GOLD Stages IV diagnosed with CHRF, already treated with nocturnal NIV and referred for a comprehensive PR program will be recruited and randomized into two groups: 1) exercise with NIV during exercise (nocturnal NIV will continue) and 2) control group - exercise without NIV during exercise (nocturnal NIV will continue).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise tolerance</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in cycle endurance time without NIV within PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Partial pressure of transcutaneous carbon dioxide</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in partial pressure of carbon dioxide levels during CET, recorded via SenTec (Switzerland, Therwill)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen saturation</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in Oxygen Saturation during CET, recorded via SenTec (Switzerland, Therwill)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in Heart Rate during CET, recorded via SenTec (Switzerland, Therwill)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial pressure of carbon dioxide</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in partial pressure of carbon dioxide pre/ post CET, recovery, isotime, recorded via capillary taken blood gases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partial pressure of oxygen</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in partial pressure of oxygen pre/ post CET, recovery, isotime, recorded via capillary taken blood gases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial blood pressure</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in arterial blood pressure pre/ post CET, recovery, isotime</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients perception - Dyspnoe</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in perceived dyspnoea /respiratory effort pre/ post CET, recovery, isotime recorded via Borg Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients perception - leg fatigue</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in perceived leg fatigue pre/ post CET, recovery, isotime recorded via Borg Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients Quality of life - Chronic Respiratory Questionnaire</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in Chronic Respiratory Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients Quality of life - Severe Respiratory Insufficiency Questionnaire</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in Severe Respiratory Insufficiency Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety and Depression</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in Hospital Anxiety and Depression Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal voluntary muscle contraction</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Change in muscle contraction force (m. rectus femoris) recorded via MicroFet</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients perception to physical Training with additional NIV</measure>
    <time_frame>Day 1 and Day 21</time_frame>
    <description>Patients in the Intervention Group will be interviewed how they perceived the Treatment, via a questionnaire with open- and closed ended questions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>cycle exercise with additional NIV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the intervention group (exercise training with non-invasive ventilation) exercise NIV pressures will be optimally adjusted to each individual patient to decrease TcPCO2 values. An IPAP of at least 15 cmH20 will be used to provide sufficient pressure to relief patients breathing muscles. Nocturnal NIV will be continued.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cycle exercise without NIV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the control Group (standard exercise training without NIV ), patients will be execute cycle exercise without additional NIV (usual care). Nocturnal NIV will be continued.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>exercise training with non-invasive ventilation</intervention_name>
    <description>In the intervention group (exercise training with non-invasive ventilation) exercise NIV pressures will be optimally adjusted to each individual patient to decrease TcPCO2 values. An IPAP of at least 15 cmH20 will be used to provide sufficient pressure to relief patients breathing muscles. Nocturnal NIV will be continued.</description>
    <arm_group_label>cycle exercise with additional NIV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>standard exercise training without NIV</intervention_name>
    <description>In the control Group (standard exercise training without NIV ), patients will be execute cycle exercise without additional NIV (usual care). Nocturnal NIV will be continued.</description>
    <arm_group_label>cycle exercise without NIV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of very severe COPD Gold Stage IV&#xD;
&#xD;
          -  Age: 40-80 years&#xD;
&#xD;
          -  PaCO2 &gt;50mmHg (at rest, during sleep or exercise)&#xD;
&#xD;
          -  Implemented nocturnal non-invasive ventilation therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant cardiovascular, orthopaedic or neurological conditions that are likely to&#xD;
             be the primary impairment to exercise performance&#xD;
&#xD;
          -  Other significant pulmonary disease which could affect exercise or NIV (e.g. asthma)&#xD;
&#xD;
          -  BMI &gt; 35 kg/m2&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Klaus Kenn, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Philipps University of Marburg, Department of pulmonary rehabilitation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Schoen Klinik Berchtesgadener Land</name>
      <address>
        <city>Schönau Am Königssee</city>
        <state>Bayern</state>
        <zip>83471</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>July 27, 2021</last_update_submitted>
  <last_update_submitted_qc>July 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Schön Klinik Berchtesgadener Land</investigator_affiliation>
    <investigator_full_name>Klaus Kenn</investigator_full_name>
    <investigator_title>Prof. Dr. Klaus Kenn</investigator_title>
  </responsible_party>
  <keyword>CHRF</keyword>
  <keyword>NIV</keyword>
  <keyword>exercise training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypercapnia</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/NCT03803358
org study id: NIV-Training
nct id: NCT03803358
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to investigate the additional effects of the use of NIV during
      exercise within a 3-week PR program on exercise capacity in COPD patients with chronic
      hypercapnic respiratory failure.
Scientific Background/ Rationale:

      Quality of life and exercise tolerance are commonly reduced in people with chronic
      obstructive pulmonary disease (COPD), especially in people with chronic hypercapnic
      respiratory failure (CHRF). Endurance exercise training as part of a pulmonary rehabilitation
      (PR) programme is an important treatment for people with COPD and has been shown to improve
      quality of life, exercise tolerance and physical activity. However, individuals with CHRF may
      have difficulties performing endurance exercise at an adequate training intensity to achieve
      the desired physiological changes.

      Non-invasive ventilation (NIV) is a method of providing breathing support using a ventilator
      and is usually delivered via a full face mask. A recent study showed that during a single
      exercise session in people with CHRF, NIV dramatically improves exercise tolerance and
      reduces breathlessness. Consequently, NIV used over a complete exercise training program may
      allow people with COPD and CHRF to exercise at a higher intensity to achieve greater
      improvement in exercise tolerance, quality of life and physical activity. So far this has
      only been tested in a small number of studies with small numbers of participants, and none
      with CHRF. It is currently not known from literature whether the demonstrated benefits of NIV
      during exercise training are clinically worthwhile or cost-effective.

      Aims The aim of the study is to investigate the additional effects of the use of NIV during
      exercise within a 3-week PR program on exercise capacity in COPD patients with chronic
      hypercapnic respiratory failure.

      Hypothesis It is assumed that a 3-week exercise training program with additional NIV, using
      titrated pressures, reduces the work of breathing. With this, it is theorized, COPD patients
      with CHRF are able to train for a longer duration and/ or with higher training intensities
      over the course of the training program and may achieve better PR outcomes.

      Primary Hypothesis:

      H.0: COPD-Patients with CHRF have the same increase in exercise capacity (endurance cycle
      time) when training with additional NIV as without NIV, during a 3-week PR program.

      H.1: COPD-Patients with CHRF have a superior increase in exercise capacity (endurance cycle
      time) when training with additional NIV as without NIV, during a 3-week PR program.

      Main Objective To determine if NIV during exercise is a useful tool for increasing exercise
      tolerance in hypercapnic patients, exercise tolerance (cycle endurance time) will be measured
      without NIV at PR admission/ discharge

      Materials and Method A total of 26 COPD patient (age: 40-80 years) in GOLD Stages IV
      diagnosed with CHRF, already treated with nocturnal NIV and referred for a comprehensive PR
      program will be recruited and randomized into two groups: 1) exercise with NIV during
      exercise (nocturnal NIV will continue) and 2) control group - exercise without NIV during
      exercise (nocturnal NIV will continue).

      Initially, patients will perform a maximum cardiopulmonary test to determine the Peak Work
      Rate (WRpeak). On a separate day, patients will perform a cycle endurance test (CET) at
      75%WRpeak without NIV using oxygen as prescribed, if needed. TcPCO2, heart rate and SpO2 via
      SenTec will be measured continuously during CET. In addition to the continuously recorded
      data, dyspnoea/ respiratory effort/ leg-fatigue (10-point Borg scale), capillary blood gases
      and the arterial blood pressure will be taken at the beginning/ end/ recovery/ isotime of the
      CET.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A total of 26 COPD patients in GOLD Stages IV diagnosed with CHRF, already treated with nocturnal NIV and referred for a comprehensive PR program will be recruited and randomized into two groups: 1) exercise with NIV during exercise (nocturnal NIV will continue) and 2) control group - exercise without NIV during exercise (nocturnal NIV will continue).
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Exercise tolerance
time frame: Day 1 and Day 21
description: Change in cycle endurance time without NIV within PR
measure: Partial pressure of transcutaneous carbon dioxide
time frame: Day 1 and Day 21
description: Change in partial pressure of carbon dioxide levels during CET, recorded via SenTec (Switzerland, Therwill)
measure: Oxygen saturation
time frame: Day 1 and Day 21
description: Change in Oxygen Saturation during CET, recorded via SenTec (Switzerland, Therwill)
measure: Heart rate
time frame: Day 1 and Day 21
description: Change in Heart Rate during CET, recorded via SenTec (Switzerland, Therwill)
measure: Partial pressure of carbon dioxide
time frame: Day 1 and Day 21
description: Change in partial pressure of carbon dioxide pre/ post CET, recovery, isotime, recorded via capillary taken blood gases
measure: Partial pressure of oxygen
time frame: Day 1 and Day 21
description: Change in partial pressure of oxygen pre/ post CET, recovery, isotime, recorded via capillary taken blood gases
measure: Arterial blood pressure
time frame: Day 1 and Day 21
description: Change in arterial blood pressure pre/ post CET, recovery, isotime
measure: Patients perception - Dyspnoe
time frame: Day 1 and Day 21
description: Change in perceived dyspnoea /respiratory effort pre/ post CET, recovery, isotime recorded via Borg Scale
measure: Patients perception - leg fatigue
time frame: Day 1 and Day 21
description: Change in perceived leg fatigue pre/ post CET, recovery, isotime recorded via Borg Scale
measure: Patients Quality of life - Chronic Respiratory Questionnaire
time frame: Day 1 and Day 21
description: Change in Chronic Respiratory Questionnaire
measure: Patients Quality of life - Severe Respiratory Insufficiency Questionnaire
time frame: Day 1 and Day 21
description: Change in Severe Respiratory Insufficiency Questionnaire
measure: Anxiety and Depression
time frame: Day 1 and Day 21
description: Change in Hospital Anxiety and Depression Scale
measure: Maximal voluntary muscle contraction
time frame: Day 1 and Day 21
description: Change in muscle contraction force (m. rectus femoris) recorded via MicroFet
measure: Patients perception to physical Training with additional NIV
time frame: Day 1 and Day 21
description: Patients in the Intervention Group will be interviewed how they perceived the Treatment, via a questionnaire with open- and closed ended questions
arm group label: cycle exercise with additional NIV
arm group type: Experimental
description: In the intervention group (exercise training with non-invasive ventilation) exercise NIV pressures will be optimally adjusted to each individual patient to decrease TcPCO2 values. An IPAP of at least 15 cmH20 will be used to provide sufficient pressure to relief patients breathing muscles. Nocturnal NIV will be continued.
arm group label: cycle exercise without NIV
arm group type: Active Comparator
description: In the control Group (standard exercise training without NIV ), patients will be execute cycle exercise without additional NIV (usual care). Nocturnal NIV will be continued.
intervention type: Other
intervention name: exercise training with non-invasive ventilation
description: In the intervention group (exercise training with non-invasive ventilation) exercise NIV pressures will be optimally adjusted to each individual patient to decrease TcPCO2 values. An IPAP of at least 15 cmH20 will be used to provide sufficient pressure to relief patients breathing muscles. Nocturnal NIV will be continued.
arm group label: cycle exercise with additional NIV
intervention type: Other
intervention name: standard exercise training without NIV
description: In the control Group (standard exercise training without NIV ), patients will be execute cycle exercise without additional NIV (usual care). Nocturnal NIV will be continued.
arm group label: cycle exercise without NIV
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Klaus Kenn, Prof. Dr.
role: Principal Investigator
affiliation: Philipps University of Marburg, Department of pulmonary rehabilitation
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Schön Klinik Berchtesgadener Land
investigator full name: Klaus Kenn
investigator title: Prof. Dr. Klaus Kenn
mesh term: Hypercapnia
sharing ipd: No