<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/NCT02252094</url>
  </required_header>
  <id_info>
    <org_study_id>NMRC/TA/0015/2013</org_study_id>
    <nct_id>NCT02252094</nct_id>
  </id_info>
  <brief_title>Ultra-protective Pulmonary Ventilation Supported by Low Flow ECCO2R for Severe ARDS</brief_title>
  <acronym>U-Protect</acronym>
  <official_title>Ultra-protective Pulmonary Ventilation Supported by Low Flow Extracorporeal Carbon Dioxide Removal (ECCO2R) and Prone Positioning for ARDS; a Pilot Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University Health System, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Baxter Healthcare Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National University Health System, Singapore</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>
      This study evaluates the use of ultra-protective ventilation, where very low ventilation&#xD;
      volumes are used, in patients with severe acute respiratory distress syndrome (ARDS) meeting&#xD;
      criteria to nurse in the prone position. Half the patients will receive ultra-protective&#xD;
      ventilation support by extracorporeal carbon dioxide removal, while the other half will&#xD;
      receive conventional lung protective ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current best practices for management of severe ARDS include lung protective ventilation and&#xD;
      nursing in the prone position. However, the best lung protective strategy is not currently&#xD;
      established and using smaller ventilation volumes than standard lung protective ventilation&#xD;
      suggest lung recovery is improved.&#xD;
&#xD;
      Application of smaller ventilation volumes requires extracorporeal carbon dioxide removal,&#xD;
      using a device similar to a dialysis to remove carbon dioxide directly from the blood. One&#xD;
      such device in the Prismalung, it removes blood through a catheter, much like a dialysis&#xD;
      catheter, pumps it through a gas exchange cartridge which removes carbon dioxide. The gas&#xD;
      exchange cartridge functions in a similar way to a dialysis filter, except it allow gases to&#xD;
      pass through, unlike dialysis filters which allow passage of fluid and small molecules.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Device no longer available in Singapore&#xD;
  </why_stopped>
  <start_date type="Actual">May 22, 2017</start_date>
  <completion_date type="Actual">May 31, 2019</completion_date>
  <primary_completion_date type="Actual">May 31, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Data analysis will be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Plateau Pressure</measure>
    <time_frame>Duration of ventilation for severe ARDS, expected average time 10 days</time_frame>
    <description>Ability to achieve a plateau pressure of &lt;/=25 cmH20 in the intervention arm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of stay in ICU stay</measure>
    <time_frame>Duration of patient stay in ICU, expected average stay 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Duration of patient stay in hospital</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Monitored for 3 months</time_frame>
    <description>ICU mortality, hospital mortality, 30 day, 60 day and 90 day mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Imaging</measure>
    <time_frame>One data set per patient during first 72 hours</time_frame>
    <description>Echocardiogram data will be collected before prone position, after prone positioning and following initiation of ultra-protective ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extracorporeal carbon dioxide removal related complications</measure>
    <time_frame>Duration of severe ARDS, expected average time frame 10 days</time_frame>
    <description>Complications or adverse events related to ECCO2R and associated anticoagulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator free days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All severe adverse events</measure>
    <time_frame>Duration of ICU stay (anticipate average stay 1-2 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patient meeting proning criteria in each group</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ability to successfully prone</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of dialysis in ICU, and ability to successfully initiate</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of referrals for ECMO</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate and reasons for declining consent to study participation</measure>
    <time_frame>First 48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Enrolment rates</measure>
    <time_frame>First 48 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung recruitability</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilation parameters</measure>
    <time_frame>Duration of mechanical ventilation</time_frame>
    <description>Data download from mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator associated pneumonia rates</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barotrauma complications</measure>
    <time_frame>Duration of ICU stay</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers of Pulmonary Inflammation</measure>
    <time_frame>Day 0, 4 and 7</time_frame>
    <description>Serum will be drawn and stored for pulmonary biomarkers analysis at the above time points</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Respiratory Distress Syndrome, Adult</condition>
  <arm_group>
    <arm_group_label>Conventional lung protective ventilation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lung protective ventilation (6ml/kg predicted body weight). All other interventions per intensive care unit standardised ARDS management protocol</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ultra-protective ventilation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultra-protective ventilation (&lt;/= 3ml/kg predicted body weight) targeting plateau pressure of &lt;/= 25 cmH2O, supported by Prismalung. All other intervention per intensive care unit standardised ARDS management protocol</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Prismalung</intervention_name>
    <description>Prism lung (Baxter Healthcare/Gambro Lund, Sweden) is an extracorporeal carbon dioxide removal device. It removes blood through a double lumen catheter and pumps it through a hollow fiber gas exchange cartridge which is impervious to fluid. Carbon dioxide diffuses out, down a concentration gradient which is maintained by sweep gas flowing through the centre of the hollow fibres. The decarboxylated blood is returned to the patient through the double lumen catheter.</description>
    <arm_group_label>Ultra-protective ventilation</arm_group_label>
    <other_name>Low flow extracorporeal carbon dioxide removal</other_name>
    <other_name>Respiratory Dialysis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ultra-protective ventilation</intervention_name>
    <description>Ventilation with &lt;/= 3ml/kg predicted body weight</description>
    <arm_group_label>Ultra-protective ventilation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional Lung Protective Ventilation</intervention_name>
    <description>Ventilation with 6ml/kg predicted body weight</description>
    <arm_group_label>Conventional lung protective ventilation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Admitted to MICU with respiratory failure and intubated&#xD;
&#xD;
          -  ARDS criteria per Berlin definition&#xD;
&#xD;
          -  PaO2:FiO2 ratio ≤ 200 mmHg for &gt; 6 hours with FiO2 ≥0.5&#xD;
&#xD;
          -  Expected to require mechanical ventilation for &gt;48 hours&#xD;
&#xD;
          -  Reversible disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anticoagulation contraindicated&#xD;
&#xD;
          -  Proven HIT&#xD;
&#xD;
          -  Unable to obtain central venous access&#xD;
&#xD;
          -  Refractory hypoxia (PaO2:FiO2 ≤80 after recruitment and proning) or other indication&#xD;
             for ECMO&#xD;
&#xD;
          -  Home oxygen use&#xD;
&#xD;
          -  Severe COPD&#xD;
&#xD;
          -  Interstitial lung disease&#xD;
&#xD;
          -  &gt; 7 days of mechanical ventilation&#xD;
&#xD;
          -  Immunocompromised patient (bone marrow, untreated HIV, PJP)&#xD;
&#xD;
          -  Advanced malignancy with life expectancy ≤ 6months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew E Cove, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ng Teng Fong General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>609606</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Terragni PP, Del Sorbo L, Mascia L, Urbino R, Martin EL, Birocco A, Faggiano C, Quintel M, Gattinoni L, Ranieri VM. Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology. 2009 Oct;111(4):826-35. doi: 10.1097/ALN.0b013e3181b764d2.</citation>
    <PMID>19741487</PMID>
  </reference>
  <reference>
    <citation>Bein T, Weber-Carstens S, Goldmann A, Muller T, Staudinger T, Brederlau J, Muellenbach R, Dembinski R, Graf BM, Wewalka M, Philipp A, Wernecke KD, Lubnow M, Slutsky AS. Lower tidal volume strategy ( approximately 3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med. 2013 May;39(5):847-56. doi: 10.1007/s00134-012-2787-6. Epub 2013 Jan 10.</citation>
    <PMID>23306584</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>September 10, 2020</last_update_submitted>
  <last_update_submitted_qc>September 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National University Health System, Singapore</investigator_affiliation>
    <investigator_full_name>Matthew COVE</investigator_full_name>
    <investigator_title>Matthew COVE</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</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/NCT02252094
org study id: NMRC/TA/0015/2013
nct id: NCT02252094
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study evaluates the use of ultra-protective ventilation, where very low ventilation
      volumes are used, in patients with severe acute respiratory distress syndrome (ARDS) meeting
      criteria to nurse in the prone position. Half the patients will receive ultra-protective
      ventilation support by extracorporeal carbon dioxide removal, while the other half will
      receive conventional lung protective ventilation.
Current best practices for management of severe ARDS include lung protective ventilation and
      nursing in the prone position. However, the best lung protective strategy is not currently
      established and using smaller ventilation volumes than standard lung protective ventilation
      suggest lung recovery is improved.

      Application of smaller ventilation volumes requires extracorporeal carbon dioxide removal,
      using a device similar to a dialysis to remove carbon dioxide directly from the blood. One
      such device in the Prismalung, it removes blood through a catheter, much like a dialysis
      catheter, pumps it through a gas exchange cartridge which removes carbon dioxide. The gas
      exchange cartridge functions in a similar way to a dialysis filter, except it allow gases to
      pass through, unlike dialysis filters which allow passage of fluid and small molecules.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Data analysis will be blinded.
measure: Plateau Pressure
time frame: Duration of ventilation for severe ARDS, expected average time 10 days
description: Ability to achieve a plateau pressure of </=25 cmH20 in the intervention arm
measure: Length of stay in ICU stay
time frame: Duration of patient stay in ICU, expected average stay 2 weeks
measure: Length of hospital stay
time frame: Duration of patient stay in hospital
measure: Mortality
time frame: Monitored for 3 months
description: ICU mortality, hospital mortality, 30 day, 60 day and 90 day mortality
measure: Cardiac Imaging
time frame: One data set per patient during first 72 hours
description: Echocardiogram data will be collected before prone position, after prone positioning and following initiation of ultra-protective ventilation
measure: Extracorporeal carbon dioxide removal related complications
time frame: Duration of severe ARDS, expected average time frame 10 days
description: Complications or adverse events related to ECCO2R and associated anticoagulation
measure: Ventilator free days
time frame: 28 days
measure: All severe adverse events
time frame: Duration of ICU stay (anticipate average stay 1-2 weeks)
measure: Number of patient meeting proning criteria in each group
time frame: Duration of ICU stay
measure: Ability to successfully prone
time frame: Duration of ICU stay
measure: Incidence of dialysis in ICU, and ability to successfully initiate
time frame: Duration of ICU stay
measure: Incidence of referrals for ECMO
time frame: Duration of ICU stay
measure: Rate and reasons for declining consent to study participation
time frame: First 48 hours
measure: Enrolment rates
time frame: First 48 hours
measure: Lung recruitability
time frame: Duration of ICU stay
measure: Ventilation parameters
time frame: Duration of mechanical ventilation
description: Data download from mechanical ventilation
measure: Ventilator associated pneumonia rates
time frame: Duration of ICU stay
measure: Barotrauma complications
time frame: Duration of ICU stay
measure: Biomarkers of Pulmonary Inflammation
time frame: Day 0, 4 and 7
description: Serum will be drawn and stored for pulmonary biomarkers analysis at the above time points
arm group label: Conventional lung protective ventilation
arm group type: Active Comparator
description: Lung protective ventilation (6ml/kg predicted body weight). All other interventions per intensive care unit standardised ARDS management protocol
arm group label: Ultra-protective ventilation
arm group type: Experimental
description: Ultra-protective ventilation (</= 3ml/kg predicted body weight) targeting plateau pressure of </= 25 cmH2O, supported by Prismalung. All other intervention per intensive care unit standardised ARDS management protocol
intervention type: Device
intervention name: Prismalung
description: Prism lung (Baxter Healthcare/Gambro Lund, Sweden) is an extracorporeal carbon dioxide removal device. It removes blood through a double lumen catheter and pumps it through a hollow fiber gas exchange cartridge which is impervious to fluid. Carbon dioxide diffuses out, down a concentration gradient which is maintained by sweep gas flowing through the centre of the hollow fibres. The decarboxylated blood is returned to the patient through the double lumen catheter.
arm group label: Ultra-protective ventilation
other name: Low flow extracorporeal carbon dioxide removal
other name: Respiratory Dialysis
intervention type: Other
intervention name: Ultra-protective ventilation
description: Ventilation with </= 3ml/kg predicted body weight
arm group label: Ultra-protective ventilation
intervention type: Other
intervention name: Conventional Lung Protective Ventilation
description: Ventilation with 6ml/kg predicted body weight
arm group label: Conventional lung protective ventilation
criteria: 
gender: All
minimum age: 21 Years
maximum age: 90 Years
healthy volunteers: No
last name: Matthew E Cove, MBChB
role: Principal Investigator
affiliation: National University Health System
facility: 
facility: 
country: Singapore
citation: Terragni PP, Del Sorbo L, Mascia L, Urbino R, Martin EL, Birocco A, Faggiano C, Quintel M, Gattinoni L, Ranieri VM. Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal. Anesthesiology. 2009 Oct;111(4):826-35. doi: 10.1097/ALN.0b013e3181b764d2.
PMID: 19741487
citation: Bein T, Weber-Carstens S, Goldmann A, Muller T, Staudinger T, Brederlau J, Muellenbach R, Dembinski R, Graf BM, Wewalka M, Philipp A, Wernecke KD, Lubnow M, Slutsky AS. Lower tidal volume strategy ( approximately 3 ml/kg) combined with extracorporeal CO2 removal versus 'conventional' protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med. 2013 May;39(5):847-56. doi: 10.1007/s00134-012-2787-6. Epub 2013 Jan 10.
PMID: 23306584
responsible party type: Principal Investigator
investigator affiliation: National University Health System, Singapore
investigator full name: Matthew COVE
investigator title: Matthew COVE
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
sharing ipd: No