<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/NCT01683669</url>
  </required_header>
  <id_info>
    <org_study_id>91/12</org_study_id>
    <nct_id>NCT01683669</nct_id>
  </id_info>
  <brief_title>Effect of Variable PSV in Acute Lung Injury: Part I and Part II</brief_title>
  <official_title>Physiological Research on Variable Pressure Support Ventilation in Patients With Acute Acute Lung Injury: Part I and Part II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Genova</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Genova</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Noisy Pressure Support Ventilation (noisy-PSV) would lead to improved lung function, while&#xD;
      preserving respiratory muscle unloading. Basically, noisy PSV differs from other assisted&#xD;
      mechanical ventilation modes that may also increase the variability of the respiratory&#xD;
      pattern (e.g. proportional assist ventilation) by the fact that the variability does not&#xD;
      depend on changes in the patient's inspiratory efforts.&#xD;
&#xD;
      The aim of this study is to evaluate the optimal variability for noisy PSV in patients with&#xD;
      ALI based on its effects on respiratory mechanics, breathing comfort, gas exchange, and&#xD;
      hemodynamics. The investigators hypothesize that noise in pressure support leads to&#xD;
      variations in VT that are able to improve lung function and that physiologic variables&#xD;
      respond differently to the degree of variability in pressure support&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect on arterial oxygenation in each setting of variability</measure>
    <time_frame>after 45 minutes of mechanical ventilation with each level of variable pressure support</time_frame>
    <description>The investigators perform an arterial blood gas and oxygenation is evaluated with PaO2/FiO2 ratio</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>work of breathing</measure>
    <time_frame>every 9 minutes, up to 45 minutes, of mechanical ventilation in each level of variable pressure support</time_frame>
    <description>work of breathing will be recorded as pressure-time product (PTP) measured on the esophageal pressure curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>effects on hemodynamic</measure>
    <time_frame>after 45 minutes of mechanical ventilation with each level of variable pressure support</time_frame>
    <description>the investigator will record blood pressure and cardiac output</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>effect on arterial carbon dioxide</measure>
    <time_frame>after 45 minutes of mechanical ventilation with each level of variable pressure support</time_frame>
    <description>The investigators perform an arterial blood gas and arterial carbon dioxide is evaluated with PaCO2.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Acute Lung Injury (ALI)</condition>
  <condition>Acute Distress Respiratory Syndrome (ARDS)</condition>
  <arm_group>
    <arm_group_label>Noisy-PSV 1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>different levels of variable pressure support</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Noisy-PSV 2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>different levels of variable pressure support</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Noisy-PSV 1</intervention_name>
    <description>Noisy-PSV 1: different levels of variable pressure support (PS) will be randomized: a) PS variability equal to 0%, b) PS variability equal to 45%, c) PS variability equal to 90%.</description>
    <arm_group_label>Noisy-PSV 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Noisy-PSV 2</intervention_name>
    <description>Noisy-PSV 2 : different levels of variable Pressure Support (PS) will be randomized: a) PS equal to Baseline and variability 0%; b) PS equal to Baseline and variability set in order achieve an increase or decrease of pressure of 5 cmH2O; c) PS equal to Baseline - 5 cmH2O and variability 0%; d) PS equal to Baseline - 5 cmH2O and set in order achieve an increase or decrease of pressure of 5 cmH2O.</description>
    <arm_group_label>Noisy-PSV 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Intubated/tracheostomized patients in assisted mechanical ventilation&#xD;
&#xD;
          -  PaO2/FiO2 100-300, with PEEP ≥ than 5 cmH2O.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  History of chronic lung disease (COPD)&#xD;
&#xD;
          -  Presence of thoracic drainage&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paolo Pelosi, Professor</last_name>
    <role>Study Director</role>
    <affiliation>University of Genoa, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Intensive Care Medicine Unit - IRCCS San Martino - IST</name>
      <address>
        <city>Genoa</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Falk DJ, Deruisseau KC, Van Gammeren DL, Deering MA, Kavazis AN, Powers SK. Mechanical ventilation promotes redox status alterations in the diaphragm. J Appl Physiol (1985). 2006 Oct;101(4):1017-24. doi: 10.1152/japplphysiol.00104.2006. Epub 2006 May 4.</citation>
    <PMID>16675618</PMID>
  </reference>
  <reference>
    <citation>Esteban A, Anzueto A, Alia I, Gordo F, Apezteguia C, Palizas F, Cide D, Goldwaser R, Soto L, Bugedo G, Rodrigo C, Pimentel J, Raimondi G, Tobin MJ. How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med. 2000 May;161(5):1450-8. doi: 10.1164/ajrccm.161.5.9902018.</citation>
    <PMID>10806138</PMID>
  </reference>
  <reference>
    <citation>Seymour CW, Frazer M, Reilly PM, Fuchs BD. Airway pressure release and biphasic intermittent positive airway pressure ventilation: are they ready for prime time? J Trauma. 2007 May;62(5):1298-308; discussion 1308-9. doi: 10.1097/TA.0b013e31803c562f.</citation>
    <PMID>17495742</PMID>
  </reference>
  <reference>
    <citation>Neumann P, Wrigge H, Zinserling J, Hinz J, Maripuu E, Andersson LG, Putensen C, Hedenstierna G. Spontaneous breathing affects the spatial ventilation and perfusion distribution during mechanical ventilatory support. Crit Care Med. 2005 May;33(5):1090-5. doi: 10.1097/01.ccm.0000163226.34868.0a.</citation>
    <PMID>15891341</PMID>
  </reference>
  <reference>
    <citation>Henzler D, Pelosi P, Bensberg R, Dembinski R, Quintel M, Pielen V, Rossaint R, Kuhlen R. Effects of partial ventilatory support modalities on respiratory function in severe hypoxemic lung injury. Crit Care Med. 2006 Jun;34(6):1738-45. doi: 10.1097/01.CCM.0000218809.49883.54.</citation>
    <PMID>16625116</PMID>
  </reference>
  <reference>
    <citation>Suki B, Alencar AM, Sujeer MK, Lutchen KR, Collins JJ, Andrade JS Jr, Ingenito EP, Zapperi S, Stanley HE. Life-support system benefits from noise. Nature. 1998 May 14;393(6681):127-8. doi: 10.1038/30130. No abstract available.</citation>
    <PMID>9603516</PMID>
  </reference>
  <reference>
    <citation>Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L370-5. doi: 10.1152/ajplung.00036.2003.</citation>
    <PMID>12851212</PMID>
  </reference>
  <reference>
    <citation>Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, Lefevre GR, Mutch WA. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002 Feb 15;165(4):456-62. doi: 10.1164/ajrccm.165.4.2108006.</citation>
    <PMID>11850336</PMID>
  </reference>
  <reference>
    <citation>Mutch WA, Lefevre GR, Cheang MS. Biologic variability in mechanical ventilation in a canine oleic acid lung injury model. Am J Respir Crit Care Med. 2001 Jun;163(7):1756-7. doi: 10.1164/ajrccm.163.7.16372c. No abstract available.</citation>
    <PMID>11401900</PMID>
  </reference>
  <reference>
    <citation>Lefevre GR, Kowalski SE, Girling LG, Thiessen DB, Mutch WA. Improved arterial oxygenation after oleic acid lung injury in the pig using a computer-controlled mechanical ventilator. Am J Respir Crit Care Med. 1996 Nov;154(5):1567-72. doi: 10.1164/ajrccm.154.5.8912782.</citation>
    <PMID>8912782</PMID>
  </reference>
  <reference>
    <citation>Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000 Jul;28(7):2457-64. doi: 10.1097/00003246-200007000-00045.</citation>
    <PMID>10921579</PMID>
  </reference>
  <reference>
    <citation>McMullen MC, Girling LG, Graham MR, Mutch WA. Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation. Anesthesiology. 2006 Jul;105(1):91-7. doi: 10.1097/00000542-200607000-00017.</citation>
    <PMID>16809999</PMID>
  </reference>
  <reference>
    <citation>Gama de Abreu M, Spieth PM, Pelosi P, Carvalho AR, Walter C, Schreiber-Ferstl A, Aikele P, Neykova B, Hubler M, Koch T. Noisy pressure support ventilation: a pilot study on a new assisted ventilation mode in experimental lung injury. Crit Care Med. 2008 Mar;36(3):818-27. doi: 10.1097/01.CCM.0000299736.55039.3A.</citation>
    <PMID>18431269</PMID>
  </reference>
  <reference>
    <citation>Spieth PM, Carvalho AR, Guldner A, Pelosi P, Kirichuk O, Koch T, de Abreu MG. Effects of different levels of pressure support variability in experimental lung injury. Anesthesiology. 2009 Feb;110(2):342-50. doi: 10.1097/ALN.0b013e318194d06e.</citation>
    <PMID>19194161</PMID>
  </reference>
  <reference>
    <citation>Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.</citation>
    <PMID>15269312</PMID>
  </reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2012</study_first_posted>
  <last_update_submitted>May 1, 2017</last_update_submitted>
  <last_update_submitted_qc>May 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Genova</investigator_affiliation>
    <investigator_full_name>Paolo Pelosi</investigator_full_name>
    <investigator_title>Full Professor - Chair of Anesthesiology and Intensive Care Medicine. Chief of Intensive Care Medicine</investigator_title>
  </responsible_party>
  <keyword>ALI</keyword>
  <keyword>ARDS</keyword>
  <keyword>Noisy pressure support ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <!-- 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/NCT01683669
org study id: 91/12
nct id: NCT01683669
lead sponsor: 
has dmc: Yes
Noisy Pressure Support Ventilation (noisy-PSV) would lead to improved lung function, while
      preserving respiratory muscle unloading. Basically, noisy PSV differs from other assisted
      mechanical ventilation modes that may also increase the variability of the respiratory
      pattern (e.g. proportional assist ventilation) by the fact that the variability does not
      depend on changes in the patient's inspiratory efforts.

      The aim of this study is to evaluate the optimal variability for noisy PSV in patients with
      ALI based on its effects on respiratory mechanics, breathing comfort, gas exchange, and
      hemodynamics. The investigators hypothesize that noise in pressure support leads to
      variations in VT that are able to improve lung function and that physiologic variables
      respond differently to the degree of variability in pressure support
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Effect on arterial oxygenation in each setting of variability
time frame: after 45 minutes of mechanical ventilation with each level of variable pressure support
description: The investigators perform an arterial blood gas and oxygenation is evaluated with PaO2/FiO2 ratio
measure: work of breathing
time frame: every 9 minutes, up to 45 minutes, of mechanical ventilation in each level of variable pressure support
description: work of breathing will be recorded as pressure-time product (PTP) measured on the esophageal pressure curve.
measure: effects on hemodynamic
time frame: after 45 minutes of mechanical ventilation with each level of variable pressure support
description: the investigator will record blood pressure and cardiac output
measure: effect on arterial carbon dioxide
time frame: after 45 minutes of mechanical ventilation with each level of variable pressure support
description: The investigators perform an arterial blood gas and arterial carbon dioxide is evaluated with PaCO2.
arm group label: Noisy-PSV 1
arm group type: Other
description: different levels of variable pressure support
arm group label: Noisy-PSV 2
arm group type: Other
description: different levels of variable pressure support
intervention type: Other
intervention name: Noisy-PSV 1
description: Noisy-PSV 1: different levels of variable pressure support (PS) will be randomized: a) PS variability equal to 0%, b) PS variability equal to 45%, c) PS variability equal to 90%.
arm group label: Noisy-PSV 1
intervention type: Other
intervention name: Noisy-PSV 2
description: Noisy-PSV 2 : different levels of variable Pressure Support (PS) will be randomized: a) PS equal to Baseline and variability 0%; b) PS equal to Baseline and variability set in order achieve an increase or decrease of pressure of 5 cmH2O; c) PS equal to Baseline - 5 cmH2O and variability 0%; d) PS equal to Baseline - 5 cmH2O and set in order achieve an increase or decrease of pressure of 5 cmH2O.
arm group label: Noisy-PSV 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Paolo Pelosi, Professor
role: Study Director
affiliation: University of Genoa, Italy
facility: 
country: Italy
citation: Falk DJ, Deruisseau KC, Van Gammeren DL, Deering MA, Kavazis AN, Powers SK. Mechanical ventilation promotes redox status alterations in the diaphragm. J Appl Physiol (1985). 2006 Oct;101(4):1017-24. doi: 10.1152/japplphysiol.00104.2006. Epub 2006 May 4.
PMID: 16675618
citation: Esteban A, Anzueto A, Alia I, Gordo F, Apezteguia C, Palizas F, Cide D, Goldwaser R, Soto L, Bugedo G, Rodrigo C, Pimentel J, Raimondi G, Tobin MJ. How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med. 2000 May;161(5):1450-8. doi: 10.1164/ajrccm.161.5.9902018.
PMID: 10806138
citation: Seymour CW, Frazer M, Reilly PM, Fuchs BD. Airway pressure release and biphasic intermittent positive airway pressure ventilation: are they ready for prime time? J Trauma. 2007 May;62(5):1298-308; discussion 1308-9. doi: 10.1097/TA.0b013e31803c562f.
PMID: 17495742
citation: Neumann P, Wrigge H, Zinserling J, Hinz J, Maripuu E, Andersson LG, Putensen C, Hedenstierna G. Spontaneous breathing affects the spatial ventilation and perfusion distribution during mechanical ventilatory support. Crit Care Med. 2005 May;33(5):1090-5. doi: 10.1097/01.ccm.0000163226.34868.0a.
PMID: 15891341
citation: Henzler D, Pelosi P, Bensberg R, Dembinski R, Quintel M, Pielen V, Rossaint R, Kuhlen R. Effects of partial ventilatory support modalities on respiratory function in severe hypoxemic lung injury. Crit Care Med. 2006 Jun;34(6):1738-45. doi: 10.1097/01.CCM.0000218809.49883.54.
PMID: 16625116
citation: Suki B, Alencar AM, Sujeer MK, Lutchen KR, Collins JJ, Andrade JS Jr, Ingenito EP, Zapperi S, Stanley HE. Life-support system benefits from noise. Nature. 1998 May 14;393(6681):127-8. doi: 10.1038/30130. No abstract available.
PMID: 9603516
citation: Arold SP, Suki B, Alencar AM, Lutchen KR, Ingenito EP. Variable ventilation induces endogenous surfactant release in normal guinea pigs. Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L370-5. doi: 10.1152/ajplung.00036.2003.
PMID: 12851212
citation: Boker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, Lefevre GR, Mutch WA. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2002 Feb 15;165(4):456-62. doi: 10.1164/ajrccm.165.4.2108006.
PMID: 11850336
citation: Mutch WA, Lefevre GR, Cheang MS. Biologic variability in mechanical ventilation in a canine oleic acid lung injury model. Am J Respir Crit Care Med. 2001 Jun;163(7):1756-7. doi: 10.1164/ajrccm.163.7.16372c. No abstract available.
PMID: 11401900
citation: Lefevre GR, Kowalski SE, Girling LG, Thiessen DB, Mutch WA. Improved arterial oxygenation after oleic acid lung injury in the pig using a computer-controlled mechanical ventilator. Am J Respir Crit Care Med. 1996 Nov;154(5):1567-72. doi: 10.1164/ajrccm.154.5.8912782.
PMID: 8912782
citation: Mutch WA, Harms S, Lefevre GR, Graham MR, Girling LG, Kowalski SE. Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome. Crit Care Med. 2000 Jul;28(7):2457-64. doi: 10.1097/00003246-200007000-00045.
PMID: 10921579
citation: McMullen MC, Girling LG, Graham MR, Mutch WA. Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation. Anesthesiology. 2006 Jul;105(1):91-7. doi: 10.1097/00000542-200607000-00017.
PMID: 16809999
citation: Gama de Abreu M, Spieth PM, Pelosi P, Carvalho AR, Walter C, Schreiber-Ferstl A, Aikele P, Neykova B, Hubler M, Koch T. Noisy pressure support ventilation: a pilot study on a new assisted ventilation mode in experimental lung injury. Crit Care Med. 2008 Mar;36(3):818-27. doi: 10.1097/01.CCM.0000299736.55039.3A.
PMID: 18431269
citation: Spieth PM, Carvalho AR, Guldner A, Pelosi P, Kirichuk O, Koch T, de Abreu MG. Effects of different levels of pressure support variability in experimental lung injury. Anesthesiology. 2009 Feb;110(2):342-50. doi: 10.1097/ALN.0b013e318194d06e.
PMID: 19194161
citation: Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.
PMID: 15269312
responsible party type: Principal Investigator
investigator affiliation: University of Genova
investigator full name: Paolo Pelosi
investigator title: Full Professor - Chair of Anesthesiology and Intensive Care Medicine. Chief of Intensive Care Medicine
mesh term: Lung Injury
mesh term: Acute Lung Injury
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Respiratory Distress Syndrome
mesh term: Wounds and Injuries