<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/NCT03041428</url>
  </required_header>
  <id_info>
    <org_study_id>FINBA_CritLab_1</org_study_id>
    <nct_id>NCT03041428</nct_id>
  </id_info>
  <brief_title>Ultra Protective Ventilation During Venoarterial Extracorporeal Membrane Oxygenation (UPV-ECMO)</brief_title>
  <acronym>UPV-ECMO</acronym>
  <official_title>Effect of Ultraprotective Ventilation on the Lung Inflammatory Response in Patients With Acute Pulmonary Edema Treated With Venoarterial Extracorporeal Oxygenation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación para la Investigación Biosanitaria del Principado de Asturias</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundación para la Investigación Biosanitaria del Principado de Asturias</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mechanical ventilation, in spite of being a life-saving technique, can also induce lung&#xD;
      injury (VILI) mediated by an inflammatory response, thus having a profound impact in the&#xD;
      course of critically ill patients. Ventilatory strategies aimed to minimize this VILI have&#xD;
      reduced mortality rates. Patients suffering cardiogenic pulmonary edema may need venoarterial&#xD;
      extracorporeal oxygenation, at the same time they are being mechanically ventilated. The&#xD;
      objective of this study is to analyze changes induced by the use of utraprotective&#xD;
      ventilatory strategies in the inflammatory lung response of these patients and their impact&#xD;
      on outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mechanical ventilation is the cornerstone of the critically-ill patients support, providing&#xD;
      better gas exchange conditions while respiratory muscles rest. Providing this life-support&#xD;
      technique may be harmful on the lung tissue, last decades research efforts were focused on&#xD;
      minimizing the ventilator-induced lung injury (VILI). Knowledge regarding the mechanisms of&#xD;
      this injury has led to changes in the clinical practice, consisting on the application of&#xD;
      positive end-expiratory pressure (PEEP) and the use of low tidal volumes, giving rise to the&#xD;
      strategy known as &quot;protective ventilation&quot;. Moreover, the use of extracorporeal membrane&#xD;
      oxygenation (ECMO) techniques contributes to maintaining an adequate gas exchange until lung&#xD;
      damage resolution. A tidal volume in the range of 6 ml/Kg of ideal body weight, with a&#xD;
      reasonable level of PEEP is the standard of care for patients with the ARDS. However, optimal&#xD;
      levels of tidal volume and PEEP have not been completely established. On the other side,&#xD;
      decreasing tidal volume below 6 ml/Kg faces its own problems. The role of the so-called&#xD;
      &quot;ultraprotective&quot; approaches, in which extracorporeal support is required to reduce tidal&#xD;
      volumes up to 3 ml/kg or less, although feasible, is currently under research. During&#xD;
      venoarterial ECMO, blood is removed from the vessels and pumped through a circuit where is&#xD;
      oxygenated and CO2 is removed; finally, the blood is returned to the arterial circulation.&#xD;
      The development of new circuits and devices made this therapy become safer and more useful,&#xD;
      improving outcomes so that its application has been widespread to many centers all over the&#xD;
      world. One of the ECMO advantages is carbon dioxide removal, which allows reducing tidal&#xD;
      volume below 6 ml/kg. Ultraprotective strategies with 3 ml/kg have demonstrated to be&#xD;
      feasible, but the additional benefit of this strategy is to be demonstrated. Therefore, in&#xD;
      this study, patients suffering cardiogenic pulmonary edema requiring ECMO and mechanical&#xD;
      ventilation are submitted to an ultraprotective ventilator strategy. Lung inflammatory&#xD;
      response is measured before and after the intervention, in order to evaluate its impact in&#xD;
      this subset of patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">December 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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in lung inflammatory mediators levels</measure>
    <time_frame>Baseline and 18 hours after the intervention</time_frame>
    <description>Bronchoalveolar lavage cytokines levels, measured in ng/ml</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Cardiogenic Pulmonary Edema</condition>
  <condition>Ventilator-Induced Lung Injury</condition>
  <condition>Extracorporeal Circulation; Complications</condition>
  <arm_group>
    <arm_group_label>Recruited patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ultraprotective ventilation</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Ultraprotective ventilation</intervention_name>
    <description>Adjusting ventilator parameters for 3 ml/kg of tidal volume in order to achieve the ultra protective strategy</description>
    <arm_group_label>Recruited patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cardiogenic pulmonary edema supported by venoarterial extracorporeal membrane&#xD;
             oxygenation.&#xD;
&#xD;
          -  Invasive mechanical ventilatory support under sedation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Immunosupresion.&#xD;
&#xD;
          -  Hemodynamic instability refractory to mechanical support, conditioning an end-of-life&#xD;
             approach and terminal situation.&#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>Guillermo M Albaiceta</last_name>
    <role>Principal Investigator</role>
    <affiliation>HUCA-FINBA, Universidad de Oviedo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias (HUCA)</name>
      <address>
        <city>Oviedo</city>
        <state>Principado De Asturias</state>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.</citation>
    <PMID>10793162</PMID>
  </reference>
  <reference>
    <citation>Leligdowicz A, Fan E. Extracorporeal life support for severe acute respiratory distress syndrome. Curr Opin Crit Care. 2015 Feb;21(1):13-9. doi: 10.1097/MCC.0000000000000170.</citation>
    <PMID>25517890</PMID>
  </reference>
  <reference>
    <citation>Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1. doi: 10.1186/cc8230. Epub 2010 Jan 7.</citation>
    <PMID>20055989</PMID>
  </reference>
  <reference>
    <citation>Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007 Jan 15;175(2):160-6. doi: 10.1164/rccm.200607-915OC. Epub 2006 Oct 12.</citation>
    <PMID>17038660</PMID>
  </reference>
  <reference>
    <citation>Figueroa-Casas JB, Montoya R. Effect of Tidal Volume Size and Its Delivery Mode on Patient-Ventilator Dyssynchrony. Ann Am Thorac Soc. 2016 Dec;13(12):2207-2214. doi: 10.1513/AnnalsATS.201605-362OC.</citation>
    <PMID>27598383</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>
  <reference>
    <citation>Fan E, Gattinoni L, Combes A, Schmidt M, Peek G, Brodie D, Muller T, Morelli A, Ranieri VM, Pesenti A, Brochard L, Hodgson C, Van Kiersbilck C, Roch A, Quintel M, Papazian L. Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts. Intensive Care Med. 2016 May;42(5):712-724. doi: 10.1007/s00134-016-4314-7. Epub 2016 Mar 23.</citation>
    <PMID>27007108</PMID>
  </reference>
  <reference>
    <citation>Schmidt M, Stewart C, Bailey M, Nieszkowska A, Kelly J, Murphy L, Pilcher D, Cooper DJ, Scheinkestel C, Pellegrino V, Forrest P, Combes A, Hodgson C. Mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study. Crit Care Med. 2015 Mar;43(3):654-64. doi: 10.1097/CCM.0000000000000753.</citation>
    <PMID>25565460</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>March 29, 2021</last_update_submitted>
  <last_update_submitted_qc>March 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Pulmonary Edema</mesh_term>
    <mesh_term>Ventilator-Induced Lung Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All datasets underlying the study are available upon request to the study principal investigators. All of the individual participant data collected during the trial, informed consent forms, study protocol, statistical analysis plan, analytic R code and raw data, are available under reasonable request, and after deindentification.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Starting 3 months after publication.</ipd_time_frame>
    <ipd_access_criteria>Principal investigators will review requests of data to be provided.</ipd_access_criteria>
  </patient_data>
  <pending_results>
    <submitted>August 22, 2022</submitted>
    <returned>July 14, 2023</returned>
  </pending_results>
  <!-- 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/NCT03041428
org study id: FINBA_CritLab_1
nct id: NCT03041428
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Mechanical ventilation, in spite of being a life-saving technique, can also induce lung
      injury (VILI) mediated by an inflammatory response, thus having a profound impact in the
      course of critically ill patients. Ventilatory strategies aimed to minimize this VILI have
      reduced mortality rates. Patients suffering cardiogenic pulmonary edema may need venoarterial
      extracorporeal oxygenation, at the same time they are being mechanically ventilated. The
      objective of this study is to analyze changes induced by the use of utraprotective
      ventilatory strategies in the inflammatory lung response of these patients and their impact
      on outcomes.
Mechanical ventilation is the cornerstone of the critically-ill patients support, providing
      better gas exchange conditions while respiratory muscles rest. Providing this life-support
      technique may be harmful on the lung tissue, last decades research efforts were focused on
      minimizing the ventilator-induced lung injury (VILI). Knowledge regarding the mechanisms of
      this injury has led to changes in the clinical practice, consisting on the application of
      positive end-expiratory pressure (PEEP) and the use of low tidal volumes, giving rise to the
      strategy known as "protective ventilation". Moreover, the use of extracorporeal membrane
      oxygenation (ECMO) techniques contributes to maintaining an adequate gas exchange until lung
      damage resolution. A tidal volume in the range of 6 ml/Kg of ideal body weight, with a
      reasonable level of PEEP is the standard of care for patients with the ARDS. However, optimal
      levels of tidal volume and PEEP have not been completely established. On the other side,
      decreasing tidal volume below 6 ml/Kg faces its own problems. The role of the so-called
      "ultraprotective" approaches, in which extracorporeal support is required to reduce tidal
      volumes up to 3 ml/kg or less, although feasible, is currently under research. During
      venoarterial ECMO, blood is removed from the vessels and pumped through a circuit where is
      oxygenated and CO2 is removed; finally, the blood is returned to the arterial circulation.
      The development of new circuits and devices made this therapy become safer and more useful,
      improving outcomes so that its application has been widespread to many centers all over the
      world. One of the ECMO advantages is carbon dioxide removal, which allows reducing tidal
      volume below 6 ml/kg. Ultraprotective strategies with 3 ml/kg have demonstrated to be
      feasible, but the additional benefit of this strategy is to be demonstrated. Therefore, in
      this study, patients suffering cardiogenic pulmonary edema requiring ECMO and mechanical
      ventilation are submitted to an ultraprotective ventilator strategy. Lung inflammatory
      response is measured before and after the intervention, in order to evaluate its impact in
      this subset of patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Change in lung inflammatory mediators levels
time frame: Baseline and 18 hours after the intervention
description: Bronchoalveolar lavage cytokines levels, measured in ng/ml
arm group label: Recruited patients
arm group type: Experimental
description: Ultraprotective ventilation
intervention type: Device
intervention name: Ultraprotective ventilation
description: Adjusting ventilator parameters for 3 ml/kg of tidal volume in order to achieve the ultra protective strategy
arm group label: Recruited patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Guillermo M Albaiceta
role: Principal Investigator
affiliation: HUCA-FINBA, Universidad de Oviedo
facility: 
country: Spain
citation: Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
PMID: 10793162
citation: Leligdowicz A, Fan E. Extracorporeal life support for severe acute respiratory distress syndrome. Curr Opin Crit Care. 2015 Feb;21(1):13-9. doi: 10.1097/MCC.0000000000000170.
PMID: 25517890
citation: Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1. doi: 10.1186/cc8230. Epub 2010 Jan 7.
PMID: 20055989
citation: Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007 Jan 15;175(2):160-6. doi: 10.1164/rccm.200607-915OC. Epub 2006 Oct 12.
PMID: 17038660
citation: Figueroa-Casas JB, Montoya R. Effect of Tidal Volume Size and Its Delivery Mode on Patient-Ventilator Dyssynchrony. Ann Am Thorac Soc. 2016 Dec;13(12):2207-2214. doi: 10.1513/AnnalsATS.201605-362OC.
PMID: 27598383
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
citation: Fan E, Gattinoni L, Combes A, Schmidt M, Peek G, Brodie D, Muller T, Morelli A, Ranieri VM, Pesenti A, Brochard L, Hodgson C, Van Kiersbilck C, Roch A, Quintel M, Papazian L. Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts. Intensive Care Med. 2016 May;42(5):712-724. doi: 10.1007/s00134-016-4314-7. Epub 2016 Mar 23.
PMID: 27007108
citation: Schmidt M, Stewart C, Bailey M, Nieszkowska A, Kelly J, Murphy L, Pilcher D, Cooper DJ, Scheinkestel C, Pellegrino V, Forrest P, Combes A, Hodgson C. Mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study. Crit Care Med. 2015 Mar;43(3):654-64. doi: 10.1097/CCM.0000000000000753.
PMID: 25565460
responsible party type: Sponsor
mesh term: Lung Injury
mesh term: Pulmonary Edema
mesh term: Ventilator-Induced Lung Injury
sharing ipd: Yes
ipd description: All datasets underlying the study are available upon request to the study principal investigators. All of the individual participant data collected during the trial, informed consent forms, study protocol, statistical analysis plan, analytic R code and raw data, are available under reasonable request, and after deindentification.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Starting 3 months after publication.
ipd access criteria: Principal investigators will review requests of data to be provided.
submitted: August 22, 2022
returned: July 14, 2023