<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/NCT04435613</url>
  </required_header>
  <id_info>
    <org_study_id>S022018</org_study_id>
    <nct_id>NCT04435613</nct_id>
  </id_info>
  <brief_title>Clinical and Physiological Assessment of a Nearly Ultra-protective Lung Ventilation Strategy: A Quasi-experimental Preliminary Study in ARDS Patients</brief_title>
  <official_title>Clinical and Physiological Assessment of a Nearly Ultra-protective Lung Ventilation Strategy: A Quasi-experimental Preliminary Study in ARDS Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clinica las Condes, Chile</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clinica las Condes, Chile</source>
  <oversight_info>
    <has_dmc>Yes</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 aims to determine whether a protective mechanical ventilator strategy generates a&#xD;
      reduction in the Bohr´s dead space in patients with moderate or severe acute respiratory&#xD;
      distress syndrome (ARDS). Commonly used ventilatory strategies in the clinical practice were&#xD;
      applied sequentially to assess their impact. Data obtained from volumetric capnography will&#xD;
      be recorded after each ventilatory strategy is applied&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protective mechanical ventilation strategies are currently the cornerstone of treatment for&#xD;
      patients undergoing mechanical ventilatory support. Among them, we can mention the reduction&#xD;
      in tidal volume, the reduction in driving pressure, the PEEP setting, and the respiratory&#xD;
      rate reduction. All of these strategies are aimed at preventing ventilator-induced lung&#xD;
      injury. Few clinical studies have evaluated the effects of protective mechanical ventilation&#xD;
      strategies on dead-space. This study was designed to evaluate dead space and alveolar&#xD;
      ventilation with a sequence of protective ventilatory strategies, keeping PEEP levels&#xD;
      constant. The ventilatory strategy was developed to reduce tidal volume, set an&#xD;
      end-inspiratory pause, and reduce the frequencies of lung tissue impact.&#xD;
&#xD;
      Baseline:&#xD;
&#xD;
      All the patients kept the variables under study constant for 60 minutes. Each of the&#xD;
      participants was studied for a period of 150 minutes. PEEP programming was set with&#xD;
      transpulmonary end-expiratory pressures to maintain between 0 and 5 cmH2O and was remained&#xD;
      constant throughout the study.&#xD;
&#xD;
      Protocol design:&#xD;
&#xD;
      Baseline: Vt 7 ml/kg/PBW Phase I: Vt 6 ml/kg/PBW. Phase II: Vt 5 ml/kg/PBW. Phase III:&#xD;
      end-inspiratory pause prolongation until achieving I:E ratio equal to 1, maintaining a&#xD;
      constant Vt level (5 ml/kg/PBW) Phase IV: Respiratory rate reduction by 20% of basal&#xD;
      conditions, maintaining constant VT level (5 ml/kg/PBW).&#xD;
&#xD;
      After 30 minutes of continuous monitoring, minute ventilation, mechanical power, variables&#xD;
      obtained by volumetric capnography, and arterial blood gases were recorded in each study&#xD;
      phase.&#xD;
&#xD;
      This study will be performed in the Intensive Care Unit of a University Hospital.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 4, 2019</start_date>
  <completion_date type="Actual">August 30, 2020</completion_date>
  <primary_completion_date type="Actual">August 29, 2020</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>
    <intervention_model_description>A quasi-experimental, non-randomized study</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To analyse the effects of different protective mechanical ventilator strategies on Bohr's dead space (VDBohr/VT) in patients with acute respiratory distress syndrome</measure>
    <time_frame>150 minutes</time_frame>
    <description>After the systematic reduction of the tidal volume, end-inspiratory pause prolongation, and the reduction of the respiratory rate, the optimisation of the dead space and the alveolar ventilation could be generated.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>ARDS</condition>
  <condition>Volumetric Capnography</condition>
  <arm_group>
    <arm_group_label>protective mechanical ventilation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Ten patients with moderate to severe ARDS were subjected to a nearly ultra-protective ventilation strategy generating a reduction in minute ventilation (Tidal volume of 5 ml/kg of predicted body weight together with a 20% reduction in respiratory rate). In addition to end-inspiratory pause, prolongation was set to avoid hypercapnia. Protocol phases: Baseline conditions: Tidal volume of 7 ml/kg. I: Tidal volume of 6 ml/kg. II: Tidal volume of 5 ml/kg. III: Increase end-inspiratory pause until achieving an I:E ratio equal to 1. IV: Respiratory rate reduction until 20% of the basal condition keeping constant I:E ratio equal to 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>protective mechanical ventilation strategies</intervention_name>
    <description>1. Reduce tidal volume from 7 ml/kg to 5 ml/kg. 2 Set end-inspiratory pausa. 3 respiratory rate reduction until 20% of the basal condition</description>
    <arm_group_label>protective mechanical ventilation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age older than 18 years&#xD;
&#xD;
          -  The requirement of invasive mechanical ventilation for more than 4 hours and less than&#xD;
             72 hours&#xD;
&#xD;
          -  Severe hypoxemia (PAFI &lt; 200) secondary to ARDS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Heart failure stage IV&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease (COPD) on home oxygen&#xD;
&#xD;
          -  Bronchopulmonary fistula&#xD;
&#xD;
          -  Hypovolemic Shock with active hemorrhage&#xD;
&#xD;
          -  Gastrointestinal bleeding&#xD;
&#xD;
          -  Oesophageal Varices&#xD;
&#xD;
          -  Nasopharynx surgery, recent oesophageal or gastric surgery&#xD;
&#xD;
          -  Massive Pulmonary Thromboembolism&#xD;
&#xD;
          -  Catastrophic respiratory failure requiring urgent extracorporeal life support&#xD;
&#xD;
          -  Respiratory acidosis. Hydrogen potential (pH) is less than 7.20 and PaCO2 higher than&#xD;
             60 mmHg at baseline.&#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>Martín Benites Albanese, Physician</last_name>
    <role>Principal Investigator</role>
    <affiliation>Critical Care Department, Clínica Las Condes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clínica Las Condes</name>
      <address>
        <city>Santiago</city>
        <state>Metropolitana</state>
        <zip>13114</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <reference>
    <citation>Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.</citation>
    <PMID>27620287</PMID>
  </reference>
  <reference>
    <citation>Tusman G, Sipmann FS, Borges JB, Hedenstierna G, Bohm SH. Validation of Bohr dead space measured by volumetric capnography. Intensive Care Med. 2011 May;37(5):870-4. doi: 10.1007/s00134-011-2164-x. Epub 2011 Feb 26.</citation>
    <PMID>21359609</PMID>
  </reference>
  <reference>
    <citation>Tusman G, Gogniat E, Bohm SH, Scandurra A, Suarez-Sipmann F, Torroba A, Casella F, Giannasi S, Roman ES. Reference values for volumetric capnography-derived non-invasive parameters in healthy individuals. J Clin Monit Comput. 2013 Jun;27(3):281-8. doi: 10.1007/s10877-013-9433-x. Epub 2013 Feb 7.</citation>
    <PMID>23389294</PMID>
  </reference>
  <reference>
    <citation>Lellouche F, Delorme M, Brochard L. Impact of Respiratory Rate and Dead Space in the Current Era of Lung Protective Mechanical Ventilation. Chest. 2020 Jul;158(1):45-47. doi: 10.1016/j.chest.2020.02.033. Epub 2020 Jul 2. No abstract available.</citation>
    <PMID>32654726</PMID>
  </reference>
  <reference>
    <citation>Astrom E, Uttman L, Niklason L, Aboab J, Brochard L, Jonson B. Pattern of inspiratory gas delivery affects CO2 elimination in health and after acute lung injury. Intensive Care Med. 2008 Feb;34(2):377-84. doi: 10.1007/s00134-007-0840-7. Epub 2007 Sep 1.</citation>
    <PMID>17763841</PMID>
  </reference>
  <reference>
    <citation>Devaquet J, Jonson B, Niklason L, Si Larbi AG, Uttman L, Aboab J, Brochard L. Effects of inspiratory pause on CO2 elimination and arterial PCO2 in acute lung injury. J Appl Physiol (1985). 2008 Dec;105(6):1944-9. doi: 10.1152/japplphysiol.90682.2008. Epub 2008 Sep 18.</citation>
    <PMID>18801962</PMID>
  </reference>
  <reference>
    <citation>Aguirre-Bermeo H, Moran I, Bottiroli M, Italiano S, Parrilla FJ, Plazolles E, Roche-Campo F, Mancebo J. End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics. Ann Intensive Care. 2016 Dec;6(1):81. doi: 10.1186/s13613-016-0183-z. Epub 2016 Aug 24.</citation>
    <PMID>27558174</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Clinica las Condes, Chile</investigator_affiliation>
    <investigator_full_name>Martin Benites</investigator_full_name>
    <investigator_title>Principal Investigator: Martín Hernán Benites Albanese</investigator_title>
  </responsible_party>
  <keyword>dead space, end-inspiratory pause, respiratory rate, ARDS</keyword>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 17, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT04435613/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04435613
org study id: S022018
nct id: NCT04435613
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to determine whether a protective mechanical ventilator strategy generates a
      reduction in the Bohr´s dead space in patients with moderate or severe acute respiratory
      distress syndrome (ARDS). Commonly used ventilatory strategies in the clinical practice were
      applied sequentially to assess their impact. Data obtained from volumetric capnography will
      be recorded after each ventilatory strategy is applied
Protective mechanical ventilation strategies are currently the cornerstone of treatment for
      patients undergoing mechanical ventilatory support. Among them, we can mention the reduction
      in tidal volume, the reduction in driving pressure, the PEEP setting, and the respiratory
      rate reduction. All of these strategies are aimed at preventing ventilator-induced lung
      injury. Few clinical studies have evaluated the effects of protective mechanical ventilation
      strategies on dead-space. This study was designed to evaluate dead space and alveolar
      ventilation with a sequence of protective ventilatory strategies, keeping PEEP levels
      constant. The ventilatory strategy was developed to reduce tidal volume, set an
      end-inspiratory pause, and reduce the frequencies of lung tissue impact.

      Baseline:

      All the patients kept the variables under study constant for 60 minutes. Each of the
      participants was studied for a period of 150 minutes. PEEP programming was set with
      transpulmonary end-expiratory pressures to maintain between 0 and 5 cmH2O and was remained
      constant throughout the study.

      Protocol design:

      Baseline: Vt 7 ml/kg/PBW Phase I: Vt 6 ml/kg/PBW. Phase II: Vt 5 ml/kg/PBW. Phase III:
      end-inspiratory pause prolongation until achieving I:E ratio equal to 1, maintaining a
      constant Vt level (5 ml/kg/PBW) Phase IV: Respiratory rate reduction by 20% of basal
      conditions, maintaining constant VT level (5 ml/kg/PBW).

      After 30 minutes of continuous monitoring, minute ventilation, mechanical power, variables
      obtained by volumetric capnography, and arterial blood gases were recorded in each study
      phase.

      This study will be performed in the Intensive Care Unit of a University Hospital.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: A quasi-experimental, non-randomized study
primary purpose: Other
masking: None (Open Label)
measure: To analyse the effects of different protective mechanical ventilator strategies on Bohr's dead space (VDBohr/VT) in patients with acute respiratory distress syndrome
time frame: 150 minutes
description: After the systematic reduction of the tidal volume, end-inspiratory pause prolongation, and the reduction of the respiratory rate, the optimisation of the dead space and the alveolar ventilation could be generated.
arm group label: protective mechanical ventilation
arm group type: Other
description: Ten patients with moderate to severe ARDS were subjected to a nearly ultra-protective ventilation strategy generating a reduction in minute ventilation (Tidal volume of 5 ml/kg of predicted body weight together with a 20% reduction in respiratory rate). In addition to end-inspiratory pause, prolongation was set to avoid hypercapnia. Protocol phases: Baseline conditions: Tidal volume of 7 ml/kg. I: Tidal volume of 6 ml/kg. II: Tidal volume of 5 ml/kg. III: Increase end-inspiratory pause until achieving an I:E ratio equal to 1. IV: Respiratory rate reduction until 20% of the basal condition keeping constant I:E ratio equal to 1
intervention type: Other
intervention name: protective mechanical ventilation strategies
description: 1. Reduce tidal volume from 7 ml/kg to 5 ml/kg. 2 Set end-inspiratory pausa. 3 respiratory rate reduction until 20% of the basal condition
arm group label: protective mechanical ventilation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martín Benites Albanese, Physician
role: Principal Investigator
affiliation: Critical Care Department, Clínica Las Condes
facility: 
country: Chile
citation: Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.
PMID: 27620287
citation: Tusman G, Sipmann FS, Borges JB, Hedenstierna G, Bohm SH. Validation of Bohr dead space measured by volumetric capnography. Intensive Care Med. 2011 May;37(5):870-4. doi: 10.1007/s00134-011-2164-x. Epub 2011 Feb 26.
PMID: 21359609
citation: Tusman G, Gogniat E, Bohm SH, Scandurra A, Suarez-Sipmann F, Torroba A, Casella F, Giannasi S, Roman ES. Reference values for volumetric capnography-derived non-invasive parameters in healthy individuals. J Clin Monit Comput. 2013 Jun;27(3):281-8. doi: 10.1007/s10877-013-9433-x. Epub 2013 Feb 7.
PMID: 23389294
citation: Lellouche F, Delorme M, Brochard L. Impact of Respiratory Rate and Dead Space in the Current Era of Lung Protective Mechanical Ventilation. Chest. 2020 Jul;158(1):45-47. doi: 10.1016/j.chest.2020.02.033. Epub 2020 Jul 2. No abstract available.
PMID: 32654726
citation: Astrom E, Uttman L, Niklason L, Aboab J, Brochard L, Jonson B. Pattern of inspiratory gas delivery affects CO2 elimination in health and after acute lung injury. Intensive Care Med. 2008 Feb;34(2):377-84. doi: 10.1007/s00134-007-0840-7. Epub 2007 Sep 1.
PMID: 17763841
citation: Devaquet J, Jonson B, Niklason L, Si Larbi AG, Uttman L, Aboab J, Brochard L. Effects of inspiratory pause on CO2 elimination and arterial PCO2 in acute lung injury. J Appl Physiol (1985). 2008 Dec;105(6):1944-9. doi: 10.1152/japplphysiol.90682.2008. Epub 2008 Sep 18.
PMID: 18801962
citation: Aguirre-Bermeo H, Moran I, Bottiroli M, Italiano S, Parrilla FJ, Plazolles E, Roche-Campo F, Mancebo J. End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics. Ann Intensive Care. 2016 Dec;6(1):81. doi: 10.1186/s13613-016-0183-z. Epub 2016 Aug 24.
PMID: 27558174
responsible party type: Principal Investigator
investigator affiliation: Clinica las Condes, Chile
investigator full name: Martin Benites
investigator title: Principal Investigator: Martín Hernán Benites Albanese
sharing ipd: Undecided
provided document: 