<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/NCT02237274</url>
  </required_header>
  <id_info>
    <org_study_id>222/13</org_study_id>
    <nct_id>NCT02237274</nct_id>
  </id_info>
  <brief_title>Cardiopulmonary Adaptation of Short Term Exposure to High Altitude in Fontan Patients: Swiss Fontan &amp; ALtitude COllaboratioN (FALCON) Study</brief_title>
  <acronym>FALCON</acronym>
  <official_title>Cardiopulmonary Adaptation of Short Term Exposure to High Altitude in Fontan Patients: Swiss Fontan &amp; ALtitude COllaboratioN (FALCON) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mach Gaensslen Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Important advances in cardiac surgery, intensive care, and diagnostic modalities over the&#xD;
      last decades have led to a steady growth in the number of adults with congenital heart&#xD;
      defects. Among adults with congenital heart disease, patients with a Fontan circulation&#xD;
      typically show the lowest values of peak oxygen consumption. For these patients, strict&#xD;
      exclusion from activities at high altitude may have an impact on quality of life. The&#xD;
      investigators aim to elucidate the short term effects of a stay at high altitude on&#xD;
      hemodynamic adaptation, exercise capacity and clinical well being in adult Fontan patients.&#xD;
      The investigators hypothesize that patients with a Fontan circulation in NYHA functional&#xD;
      class I-II are able to increase their cardiac output during exercise at high altitude in&#xD;
      order to meet the required metabolic demands and therefore tolerate the journey to the&#xD;
      Jungfraujoch well.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Important advances in cardiac surgery, intensive care, and diagnostic modalities over the&#xD;
      last decades have led to a steady growth in the number of adults with congenital heart&#xD;
      defects (Grown-up congenital heart disease GUCH). Among adults with congenital heart disease,&#xD;
      patients with a Fontan circulation typically show the lowest values of peak oxygen&#xD;
      consumption with peak VO2 values between 15 and 29 ml/kg/min, corresponding to 43-64 % of the&#xD;
      predicted values in healthy controls. For these patients, strict exclusion from activities at&#xD;
      high altitude may have an impact on quality of life. Unfortunately, the most recent&#xD;
      recommendations for physical activity, recreation sport, and exercise training in paediatric&#xD;
      patients with congenital heart disease do not provide specific recommendations. The&#xD;
      investigators study therefore aims to elucidate the short term effects of a stay at high&#xD;
      altitude on hemodynamic adaptation, exercise capacity and clinical well being in adult Fontan&#xD;
      patients. These results are necessary to counsel GUCH patients with respect to their leasure&#xD;
      activities in Switzerland.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The aims of the study are to measure a)the hemodynamic adaptation (pulmonary blood flow) at&#xD;
      rest and during exercise; b)the response of cardiopulmonary parameters to exercise&#xD;
      (ventilation, O2 uptake) and c) heart rate variability and occurrence of arrhythmias during&#xD;
      the journey and while performing study measures in patients with a Fontan circulation. The&#xD;
      measurements will be performed at high altitude and at lowland and compared with an age- and&#xD;
      gender-matched control group of healthy subjects. The objective is to test the clinical&#xD;
      tolerance of high altitude exposure after a rapid ascent with public transport in patients&#xD;
      with a Fontan circulation. The investigators hypothesize that patients with a Fontan&#xD;
      circulation in NYHA functional class I-II are able to increase their cardiac output during&#xD;
      exercise at high altitude in order to meet the required metabolic demands despite hypoxia&#xD;
      induced pulmonary vasoconstriction and therefore tolerate the journey to the Jungfraujoch&#xD;
      well.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      The investigators aim to include 30 patients with a Fontan circulation and 30 age and&#xD;
      gender-matched healthy adults. Baseline testing in Bern (540m over sea level)includes: a&#xD;
      symptom limited cardiopulmonary exercise stress test on a cycle ergometer with a ramp&#xD;
      protocol (CPX); a pulmonary function test (spirometry); a symptom limited, stepwise&#xD;
      increasing workload test with non-invasive inert gas rebreathing method for pulmonary blood&#xD;
      flow measurement during exercise (Innocor®); analysis of heart rate variability (HRV);&#xD;
      Holter-ECG monitoring for detection of arrhythmias.&#xD;
&#xD;
      Within a time period of 12 weeks, the baseline tests will be repeated on the Jungfraujoch&#xD;
      (3454m).&#xD;
&#xD;
      The primary endpoint of this study is the increase of pulmonary blood flow during exercise in&#xD;
      response to high altitude exposure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in pulmonary blood flow during exercise at high altitude</measure>
    <time_frame>During exercise at high altitude, maximum 12 weeks after baseline measurements</time_frame>
    <description>Pulmonary blood flow measurement during exercise: a symptom limited, stepwise increasing workload test with non-invasive inert gas rebreathing method for (Innocor®)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in peak VO2 (exercise capacity)</measure>
    <time_frame>During exercise at high altitude, maximum 12 weeks after baseline measurements</time_frame>
    <description>Peak VO2 (exercise capacity): a symptom limited cardiopulmonary exercise stress test on a cycle ergometer with a ramp protocol (CPX)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in clinical symptoms (tolerance of high alt. exposure, funct.l NYHA class, dyspnea Borg scale)</measure>
    <time_frame>During exercise at high altitude, maximum 12 weeks after baseline measurements</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in sympathovagal balance of the autonomic nervous system</measure>
    <time_frame>During exercise at high altitude, maximum 12 weeks after baseline measurements</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in occurrence of arrhythmias</measure>
    <time_frame>During exercise at high altitude, maximum 12 weeks after baseline measurements</time_frame>
    <description>Measured by holter-ECG monitoring</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Fontan Procedure</condition>
  <condition>Altitude</condition>
  <arm_group>
    <arm_group_label>Patients with Fontan circulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High altitude exposition</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Age and gender-matched healthy volunteers</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>High altitude exposition</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High altitude exposition</intervention_name>
    <description>High altitude exposition</description>
    <arm_group_label>Age and gender-matched healthy volunteers</arm_group_label>
    <arm_group_label>Patients with Fontan circulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age above 18years&#xD;
&#xD;
          -  Congenital heart disease and Fontan circulation&#xD;
&#xD;
          -  NYHA functional class I &amp; II&#xD;
&#xD;
          -  Peak VO2 &gt; 45% of predicted&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &quot;Failing Fontan&quot;, peak VO2 &lt; 45% of predicted&#xD;
&#xD;
          -  Significant right-to-left shunt&#xD;
&#xD;
          -  Baseline arterial O2 saturation at rest &lt;90% at room air&#xD;
&#xD;
          -  Hospitalization within the last 3 months for cardiac reasons&#xD;
&#xD;
          -  Decrease in functional NYHA class within the last 3 months&#xD;
&#xD;
          -  Motor skill inability to perform a maximal exercise stress test&#xD;
&#xD;
          -  Respiratory Exchange Ratio &lt; 1&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Markus Schwerzmann, Professor, Dr med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Cardiology, GUCH, Bern University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Cardiology, GUCH, Bern University Hospital</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <results_reference>
    <citation>Bartsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation. 2007 Nov 6;116(19):2191-202. doi: 10.1161/CIRCULATIONAHA.106.650796. No abstract available.</citation>
    <PMID>17984389</PMID>
  </results_reference>
  <results_reference>
    <citation>Fredriksen PM, Veldtman G, Hechter S, Therrien J, Chen A, Warsi MA, Freeman M, Liu P, Siu S, Thaulow E, Webb G. Aerobic capacity in adults with various congenital heart diseases. Am J Cardiol. 2001 Feb 1;87(3):310-4. doi: 10.1016/s0002-9149(00)01364-3.</citation>
    <PMID>11165966</PMID>
  </results_reference>
  <results_reference>
    <citation>Driscoll DJ, Durongpisitkul K. Exercise testing after the Fontan operation. Pediatr Cardiol. 1999 Jan-Feb;20(1):57-9; discussion 60. doi: 10.1007/s002469900397. No abstract available.</citation>
    <PMID>9861079</PMID>
  </results_reference>
  <results_reference>
    <citation>Freedom RM, Hamilton R, Yoo SJ, Mikailian H, Benson L, McCrindle B, Justino H, Williams WG. The Fontan procedure: analysis of cohorts and late complications. Cardiol Young. 2000 Oct;10(4):307-31. doi: 10.1017/s1047951100009616. No abstract available.</citation>
    <PMID>10950328</PMID>
  </results_reference>
  <results_reference>
    <citation>Takken T, Giardini A, Reybrouck T, Gewillig M, Hovels-Gurich HH, Longmuir PE, McCrindle BW, Paridon SM, Hager A. Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease: a report from the Exercise, Basic &amp; Translational Research Section of the European Association of Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and Lung Exercise Group, and the Association for European Paediatric Cardiology. Eur J Prev Cardiol. 2012 Oct;19(5):1034-65. doi: 10.1177/1741826711420000.</citation>
    <PMID>23126001</PMID>
  </results_reference>
  <results_reference>
    <citation>Rimoldi SF, Sartori C, Seiler C, Delacretaz E, Mattle HP, Scherrer U, Allemann Y. High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations. Prog Cardiovasc Dis. 2010 May-Jun;52(6):512-24. doi: 10.1016/j.pcad.2010.03.005.</citation>
    <PMID>20417345</PMID>
  </results_reference>
  <results_reference>
    <citation>Luks AM, Stout K, Swenson ER. Evaluating the safety of high-altitude travel in patients with adult congenital heart disease. Congenit Heart Dis. 2010 May-Jun;5(3):220-32. doi: 10.1111/j.1747-0803.2010.00415.x.</citation>
    <PMID>20576041</PMID>
  </results_reference>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>February 20, 2015</last_update_submitted>
  <last_update_submitted_qc>February 20, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 23, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fontan circulation</keyword>
  <keyword>High altitude exposure</keyword>
  <!-- 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/NCT02237274
org study id: 222/13
nct id: NCT02237274
lead sponsor: 
collaborator: 
has dmc: No
Important advances in cardiac surgery, intensive care, and diagnostic modalities over the
      last decades have led to a steady growth in the number of adults with congenital heart
      defects. Among adults with congenital heart disease, patients with a Fontan circulation
      typically show the lowest values of peak oxygen consumption. For these patients, strict
      exclusion from activities at high altitude may have an impact on quality of life. The
      investigators aim to elucidate the short term effects of a stay at high altitude on
      hemodynamic adaptation, exercise capacity and clinical well being in adult Fontan patients.
      The investigators hypothesize that patients with a Fontan circulation in NYHA functional
      class I-II are able to increase their cardiac output during exercise at high altitude in
      order to meet the required metabolic demands and therefore tolerate the journey to the
      Jungfraujoch well.
Background:

      Important advances in cardiac surgery, intensive care, and diagnostic modalities over the
      last decades have led to a steady growth in the number of adults with congenital heart
      defects (Grown-up congenital heart disease GUCH). Among adults with congenital heart disease,
      patients with a Fontan circulation typically show the lowest values of peak oxygen
      consumption with peak VO2 values between 15 and 29 ml/kg/min, corresponding to 43-64 % of the
      predicted values in healthy controls. For these patients, strict exclusion from activities at
      high altitude may have an impact on quality of life. Unfortunately, the most recent
      recommendations for physical activity, recreation sport, and exercise training in paediatric
      patients with congenital heart disease do not provide specific recommendations. The
      investigators study therefore aims to elucidate the short term effects of a stay at high
      altitude on hemodynamic adaptation, exercise capacity and clinical well being in adult Fontan
      patients. These results are necessary to counsel GUCH patients with respect to their leasure
      activities in Switzerland.

      Objective:

      The aims of the study are to measure a)the hemodynamic adaptation (pulmonary blood flow) at
      rest and during exercise; b)the response of cardiopulmonary parameters to exercise
      (ventilation, O2 uptake) and c) heart rate variability and occurrence of arrhythmias during
      the journey and while performing study measures in patients with a Fontan circulation. The
      measurements will be performed at high altitude and at lowland and compared with an age- and
      gender-matched control group of healthy subjects. The objective is to test the clinical
      tolerance of high altitude exposure after a rapid ascent with public transport in patients
      with a Fontan circulation. The investigators hypothesize that patients with a Fontan
      circulation in NYHA functional class I-II are able to increase their cardiac output during
      exercise at high altitude in order to meet the required metabolic demands despite hypoxia
      induced pulmonary vasoconstriction and therefore tolerate the journey to the Jungfraujoch
      well.

      Methods:

      The investigators aim to include 30 patients with a Fontan circulation and 30 age and
      gender-matched healthy adults. Baseline testing in Bern (540m over sea level)includes: a
      symptom limited cardiopulmonary exercise stress test on a cycle ergometer with a ramp
      protocol (CPX); a pulmonary function test (spirometry); a symptom limited, stepwise
      increasing workload test with non-invasive inert gas rebreathing method for pulmonary blood
      flow measurement during exercise (Innocor®); analysis of heart rate variability (HRV);
      Holter-ECG monitoring for detection of arrhythmias.

      Within a time period of 12 weeks, the baseline tests will be repeated on the Jungfraujoch
      (3454m).

      The primary endpoint of this study is the increase of pulmonary blood flow during exercise in
      response to high altitude exposure.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Change from baseline in pulmonary blood flow during exercise at high altitude
time frame: During exercise at high altitude, maximum 12 weeks after baseline measurements
description: Pulmonary blood flow measurement during exercise: a symptom limited, stepwise increasing workload test with non-invasive inert gas rebreathing method for (Innocor®)
measure: Change from baseline in peak VO2 (exercise capacity)
time frame: During exercise at high altitude, maximum 12 weeks after baseline measurements
description: Peak VO2 (exercise capacity): a symptom limited cardiopulmonary exercise stress test on a cycle ergometer with a ramp protocol (CPX)
measure: Change from baseline in clinical symptoms (tolerance of high alt. exposure, funct.l NYHA class, dyspnea Borg scale)
time frame: During exercise at high altitude, maximum 12 weeks after baseline measurements
measure: Change from baseline in sympathovagal balance of the autonomic nervous system
time frame: During exercise at high altitude, maximum 12 weeks after baseline measurements
measure: Change from baseline in occurrence of arrhythmias
time frame: During exercise at high altitude, maximum 12 weeks after baseline measurements
description: Measured by holter-ECG monitoring
arm group label: Patients with Fontan circulation
arm group type: Experimental
description: High altitude exposition
arm group label: Age and gender-matched healthy volunteers
arm group type: Other
description: High altitude exposition
intervention type: Other
intervention name: High altitude exposition
description: High altitude exposition
arm group label: Age and gender-matched healthy volunteers
arm group label: Patients with Fontan circulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Markus Schwerzmann, Professor, Dr med.
role: Principal Investigator
affiliation: Department of Cardiology, GUCH, Bern University Hospital
facility: 
country: Switzerland
citation: Bartsch P, Gibbs JS. Effect of altitude on the heart and the lungs. Circulation. 2007 Nov 6;116(19):2191-202. doi: 10.1161/CIRCULATIONAHA.106.650796. No abstract available.
PMID: 17984389
citation: Fredriksen PM, Veldtman G, Hechter S, Therrien J, Chen A, Warsi MA, Freeman M, Liu P, Siu S, Thaulow E, Webb G. Aerobic capacity in adults with various congenital heart diseases. Am J Cardiol. 2001 Feb 1;87(3):310-4. doi: 10.1016/s0002-9149(00)01364-3.
PMID: 11165966
citation: Driscoll DJ, Durongpisitkul K. Exercise testing after the Fontan operation. Pediatr Cardiol. 1999 Jan-Feb;20(1):57-9; discussion 60. doi: 10.1007/s002469900397. No abstract available.
PMID: 9861079
citation: Freedom RM, Hamilton R, Yoo SJ, Mikailian H, Benson L, McCrindle B, Justino H, Williams WG. The Fontan procedure: analysis of cohorts and late complications. Cardiol Young. 2000 Oct;10(4):307-31. doi: 10.1017/s1047951100009616. No abstract available.
PMID: 10950328
citation: Takken T, Giardini A, Reybrouck T, Gewillig M, Hovels-Gurich HH, Longmuir PE, McCrindle BW, Paridon SM, Hager A. Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease: a report from the Exercise, Basic & Translational Research Section of the European Association of Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and Lung Exercise Group, and the Association for European Paediatric Cardiology. Eur J Prev Cardiol. 2012 Oct;19(5):1034-65. doi: 10.1177/1741826711420000.
PMID: 23126001
citation: Rimoldi SF, Sartori C, Seiler C, Delacretaz E, Mattle HP, Scherrer U, Allemann Y. High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations. Prog Cardiovasc Dis. 2010 May-Jun;52(6):512-24. doi: 10.1016/j.pcad.2010.03.005.
PMID: 20417345
citation: Luks AM, Stout K, Swenson ER. Evaluating the safety of high-altitude travel in patients with adult congenital heart disease. Congenit Heart Dis. 2010 May-Jun;5(3):220-32. doi: 10.1111/j.1747-0803.2010.00415.x.
PMID: 20576041
responsible party type: Sponsor