<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/NCT03296293</url>
  </required_header>
  <id_info>
    <org_study_id>ZhoupuH</org_study_id>
    <nct_id>NCT03296293</nct_id>
  </id_info>
  <brief_title>Effects of Positive End-expiratory Pressure on Intracranial Pressure in Patients With Severe Traumatic Brain Injury</brief_title>
  <acronym>PEEP，ICP，CVP</acronym>
  <official_title>Doctor of Department of Emergency and Critical Care Medicine, Zhoupu Hospital Affiliated With Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hongpeng Li</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhoupu Hospital, Pudong New Area, Shanghai, China</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>
      The impact of PEEP on ICP was dependent on the difference between elevated CVP levels and&#xD;
      baseline ICP levels. ICP would increase once elevated CVP through PEEP adjustment exceeds the&#xD;
      baseline ICP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      all patients were exposed to incremental PEEP levels of 0, 5, 10, and 15cmH2O with 100% of&#xD;
      FiO2. The measurements were done bedside on stabilized hemodynamics and intracranial&#xD;
      pressure. The measurement was discontinued if the following situation presented and remedies&#xD;
      were applied accordingly: (1) CPP &lt; 60 mmHg (norepinephrine at 0.3~1.0μg/kg.min was used);&#xD;
      (2) ICP &gt; 25 mmHg (PEEP was restored to 0); (3) increase of pressure plateau &gt; 35 cmH2O&#xD;
      (tidal volume was decreased and PetCO2 was maintained at 30~35mmHg); (4) SpO2 &lt; 90% (PEEP was&#xD;
      restored to 0); and (5) suspicion of pneumothorax (PEEP was restored to 0 and chest&#xD;
      radiography was performed). An equilibration period (at least 90 seconds) was entailed to&#xD;
      ensure a normalized baseline PetCO2 through modulating tidal volume and respiratory rate.&#xD;
&#xD;
      ICP, CVP, Pj, and MAP were measured twice or more at each level of PEEP for consecutively&#xD;
      five days after admission. CPP was calculated according to the following equation:&#xD;
      CPP=MAP-ICP. The difference between baseline ICP and CVP was categorized into the following&#xD;
      three groups according to the previous findings: Group I,IVPD ≤ 3mmHg, Group II, 3 &lt; IVPD ≤ 6&#xD;
      mmHg, Group III, IVPD &gt; 6 mmHg. Relationships between PEEP and ICP, CVP and MAP, CVP and Pj&#xD;
      were analyzed in each group respectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2016</start_date>
  <completion_date type="Actual">August 1, 2017</completion_date>
  <primary_completion_date type="Actual">June 15, 2017</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of positive end-expiratory pressure on intracranial pressure in patients with severe traumatic brain injury</measure>
    <time_frame>up to 12 months</time_frame>
    <description>The impact of PEEP on ICP was dependent on the difference between elevated CVP levels and baseline ICP levels. ICP would increase once elevated CVP through PEEP adjustment exceeds the baseline ICP.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <condition>Mechanical Ventilation Complication</condition>
  <arm_group>
    <arm_group_label>Group I:IVPD≤3mmHg</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Effect of PEEP at 5cmH2O on ICP in Group I:IVPD≤3mmHg Effect of PEEP at 10cmH2O on ICP in Group I:IVPD≤3mmHg Effect of PEEP at 15cmH2O on ICP in Group I:IVPD≤3mmHg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II:3mmHg&lt;IVPD≤6mmHg</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Effect of PEEP at 5cmH2O on ICP in Group II:3mmHg&lt;IVPD≤6mmHg Effect of PEEP at 10cmH2O on ICP in Group II:3mmHg&lt;IVPD≤6mmHg Effect of PEEP at 15cmH2O on ICP in Group II:3mmHg&lt;IVPD≤6mmHg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group III:IVPD&gt;6mmHg</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Effect of PEEP at 5cmH2O on ICP in Group III:IVPD&gt;6mmHg Effect of PEEP at 10cmH2O on ICP in Group III:IVPD&gt;6mmHg Effect of PEEP at 15cmH2O on ICP in Group III:IVPD&gt;6mmHg</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PEEP at 5cmH2O</intervention_name>
    <description>Effect of PEEP at 5cmH2O on ICP</description>
    <arm_group_label>Group I:IVPD≤3mmHg</arm_group_label>
    <arm_group_label>Group II:3mmHg&lt;IVPD≤6mmHg</arm_group_label>
    <arm_group_label>Group III:IVPD&gt;6mmHg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PEEP at 10cmH2O</intervention_name>
    <description>Effect of PEEP at 10cmH2O on ICP</description>
    <arm_group_label>Group I:IVPD≤3mmHg</arm_group_label>
    <arm_group_label>Group II:3mmHg&lt;IVPD≤6mmHg</arm_group_label>
    <arm_group_label>Group III:IVPD&gt;6mmHg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PEEP at 15cmH2O</intervention_name>
    <description>Effect of PEEP at 15cmH2O on ICP</description>
    <arm_group_label>Group I:IVPD≤3mmHg</arm_group_label>
    <arm_group_label>Group II:3mmHg&lt;IVPD≤6mmHg</arm_group_label>
    <arm_group_label>Group III:IVPD&gt;6mmHg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients diagnosed with sTBI (GCS≤8) and applied with MV were initially included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Brain death&#xD;
&#xD;
          -  Younger than 18 or older than 80 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Hemodynamic instability：for example heart rate &gt;120 bpm or CPP &lt;60 mmHg&#xD;
&#xD;
          -  Bulbous lung or pneumothorax&#xD;
&#xD;
          -  Myocardial infarction&#xD;
&#xD;
          -  Refusal of consent&#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>Hongpeng Li, master</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Emergency and Critical Care Medicine, Zhoupu Hospital affiliated with Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China</affiliation>
  </overall_official>
  <results_reference>
    <citation>Nemer SN, Caldeira JB, Santos RG, Guimaraes BL, Garcia JM, Prado D, Silva RT, Azeredo LM, Faria ER, Souza PC. Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study. J Crit Care. 2015 Dec;30(6):1263-6. doi: 10.1016/j.jcrc.2015.07.019. Epub 2015 Jul 26.</citation>
    <PMID>26307004</PMID>
  </results_reference>
  <results_reference>
    <citation>Muench E, Bauhuf C, Roth H, Horn P, Phillips M, Marquetant N, Quintel M, Vajkoczy P. Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation. Crit Care Med. 2005 Oct;33(10):2367-72. doi: 10.1097/01.ccm.0000181732.37319.df.</citation>
    <PMID>16215394</PMID>
  </results_reference>
  <results_reference>
    <citation>Boone MD, Jinadasa SP, Mueller A, Shaefi S, Kasper EM, Hanafy KA, O'Gara BP, Talmor DS. The Effect of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics. Neurocrit Care. 2017 Apr;26(2):174-181. doi: 10.1007/s12028-016-0328-9.</citation>
    <PMID>27848125</PMID>
  </results_reference>
  <results_reference>
    <citation>Ropper AH, O'Rourke D, Kennedy SK. Head position, intracranial pressure, and compliance. Neurology. 1982 Nov;32(11):1288-91. doi: 10.1212/wnl.32.11.1288.</citation>
    <PMID>6890165</PMID>
  </results_reference>
  <results_reference>
    <citation>Shojaee M, Sabzghabaei A, Alimohammadi H, Derakhshanfar H, Amini A, Esmailzadeh B. Effect of Positive End-Expiratory Pressure on Central Venous Pressure in Patients under Mechanical Ventilation. Emerg (Tehran). 2017;5(1):e1. Epub 2017 Jan 8.</citation>
    <PMID>28286808</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>September 28, 2017</last_update_submitted>
  <last_update_submitted_qc>September 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Zhoupu Hospital, Pudong New Area, Shanghai, China</investigator_affiliation>
    <investigator_full_name>Hongpeng Li</investigator_full_name>
    <investigator_title>medicine master</investigator_title>
  </responsible_party>
  <keyword>Positive end-expiratory pressure(PEEP)</keyword>
  <keyword>intracranial pressure(ICP)</keyword>
  <keyword>central venous pressure(CVP)</keyword>
  <keyword>intracranial central venous pressure difference(IVPD)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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>December 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03296293/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/NCT03296293
org study id: ZhoupuH
nct id: NCT03296293
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The impact of PEEP on ICP was dependent on the difference between elevated CVP levels and
      baseline ICP levels. ICP would increase once elevated CVP through PEEP adjustment exceeds the
      baseline ICP.
all patients were exposed to incremental PEEP levels of 0, 5, 10, and 15cmH2O with 100% of
      FiO2. The measurements were done bedside on stabilized hemodynamics and intracranial
      pressure. The measurement was discontinued if the following situation presented and remedies
      were applied accordingly: (1) CPP < 60 mmHg (norepinephrine at 0.3~1.0μg/kg.min was used);
      (2) ICP > 25 mmHg (PEEP was restored to 0); (3) increase of pressure plateau > 35 cmH2O
      (tidal volume was decreased and PetCO2 was maintained at 30~35mmHg); (4) SpO2 < 90% (PEEP was
      restored to 0); and (5) suspicion of pneumothorax (PEEP was restored to 0 and chest
      radiography was performed). An equilibration period (at least 90 seconds) was entailed to
      ensure a normalized baseline PetCO2 through modulating tidal volume and respiratory rate.

      ICP, CVP, Pj, and MAP were measured twice or more at each level of PEEP for consecutively
      five days after admission. CPP was calculated according to the following equation:
      CPP=MAP-ICP. The difference between baseline ICP and CVP was categorized into the following
      three groups according to the previous findings: Group I,IVPD ≤ 3mmHg, Group II, 3 < IVPD ≤ 6
      mmHg, Group III, IVPD > 6 mmHg. Relationships between PEEP and ICP, CVP and MAP, CVP and Pj
      were analyzed in each group respectively.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Effects of positive end-expiratory pressure on intracranial pressure in patients with severe traumatic brain injury
time frame: up to 12 months
description: The impact of PEEP on ICP was dependent on the difference between elevated CVP levels and baseline ICP levels. ICP would increase once elevated CVP through PEEP adjustment exceeds the baseline ICP.
arm group label: Group I:IVPD≤3mmHg
arm group type: Other
description: Effect of PEEP at 5cmH2O on ICP in Group I:IVPD≤3mmHg Effect of PEEP at 10cmH2O on ICP in Group I:IVPD≤3mmHg Effect of PEEP at 15cmH2O on ICP in Group I:IVPD≤3mmHg
arm group label: Group II:3mmHg<IVPD≤6mmHg
arm group type: Other
description: Effect of PEEP at 5cmH2O on ICP in Group II:3mmHg<IVPD≤6mmHg Effect of PEEP at 10cmH2O on ICP in Group II:3mmHg<IVPD≤6mmHg Effect of PEEP at 15cmH2O on ICP in Group II:3mmHg<IVPD≤6mmHg
arm group label: Group III:IVPD>6mmHg
arm group type: Other
description: Effect of PEEP at 5cmH2O on ICP in Group III:IVPD>6mmHg Effect of PEEP at 10cmH2O on ICP in Group III:IVPD>6mmHg Effect of PEEP at 15cmH2O on ICP in Group III:IVPD>6mmHg
intervention type: Other
intervention name: PEEP at 5cmH2O
description: Effect of PEEP at 5cmH2O on ICP
arm group label: Group I:IVPD≤3mmHg
arm group label: Group II:3mmHg<IVPD≤6mmHg
arm group label: Group III:IVPD>6mmHg
intervention type: Other
intervention name: PEEP at 10cmH2O
description: Effect of PEEP at 10cmH2O on ICP
arm group label: Group I:IVPD≤3mmHg
arm group label: Group II:3mmHg<IVPD≤6mmHg
arm group label: Group III:IVPD>6mmHg
intervention type: Other
intervention name: PEEP at 15cmH2O
description: Effect of PEEP at 15cmH2O on ICP
arm group label: Group I:IVPD≤3mmHg
arm group label: Group II:3mmHg<IVPD≤6mmHg
arm group label: Group III:IVPD>6mmHg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Hongpeng Li, master
role: Principal Investigator
affiliation: Department of Emergency and Critical Care Medicine, Zhoupu Hospital affiliated with Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China
citation: Nemer SN, Caldeira JB, Santos RG, Guimaraes BL, Garcia JM, Prado D, Silva RT, Azeredo LM, Faria ER, Souza PC. Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study. J Crit Care. 2015 Dec;30(6):1263-6. doi: 10.1016/j.jcrc.2015.07.019. Epub 2015 Jul 26.
PMID: 26307004
citation: Muench E, Bauhuf C, Roth H, Horn P, Phillips M, Marquetant N, Quintel M, Vajkoczy P. Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation. Crit Care Med. 2005 Oct;33(10):2367-72. doi: 10.1097/01.ccm.0000181732.37319.df.
PMID: 16215394
citation: Boone MD, Jinadasa SP, Mueller A, Shaefi S, Kasper EM, Hanafy KA, O'Gara BP, Talmor DS. The Effect of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics. Neurocrit Care. 2017 Apr;26(2):174-181. doi: 10.1007/s12028-016-0328-9.
PMID: 27848125
citation: Ropper AH, O'Rourke D, Kennedy SK. Head position, intracranial pressure, and compliance. Neurology. 1982 Nov;32(11):1288-91. doi: 10.1212/wnl.32.11.1288.
PMID: 6890165
citation: Shojaee M, Sabzghabaei A, Alimohammadi H, Derakhshanfar H, Amini A, Esmailzadeh B. Effect of Positive End-Expiratory Pressure on Central Venous Pressure in Patients under Mechanical Ventilation. Emerg (Tehran). 2017;5(1):e1. Epub 2017 Jan 8.
PMID: 28286808
responsible party type: Sponsor-Investigator
investigator affiliation: Zhoupu Hospital, Pudong New Area, Shanghai, China
investigator full name: Hongpeng Li
investigator title: medicine master
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
sharing ipd: No
provided document: 