<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/NCT03245684</url>
  </required_header>
  <id_info>
    <org_study_id>ASCOVENT</org_study_id>
    <nct_id>NCT03245684</nct_id>
  </id_info>
  <brief_title>Assisted or Controlled Ventilation in Ards (Ascovent)</brief_title>
  <acronym>ASCOVENT</acronym>
  <official_title>Assessment of the Inflammatory Response Associated With the Increase of Transpulmonary Pressure in Ipoxiemic Patients During Assisted Mechanical Ventilation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Roma La Sapienza</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 present pilot randomized controlled clinical trial will test the hypothesis that in&#xD;
      patients with ARDS, fixing ventilator settings to the conventional protective ventilatory&#xD;
      strategy (VT 6 ml/kg ideal body weight and Pplat ≤ 30 cmH2O, PEEP according the PEEP/FiO2&#xD;
      table), control modes of mechanical ventilation will be associated to a concentration of&#xD;
      pulmonary and systemic inflammatory mediators lower than the concentration of inflammatory&#xD;
      mediators observed during assisted modes of mechanical ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All patients will be treated according to the sedation protocols and standards of care.&#xD;
      Sedation will be guaranteed by continuous infusion of Propofol 2-4 ml / Kg / h, Remifentanil&#xD;
      0.05-0.1 mcg / Kg / min to obtain a RASS scale level of -5 of the RASS. Mio-resolution&#xD;
      eventually obtained by a loading dose of 15 mg e.v. followed by a continuous infusion of 37.5&#xD;
      mg / h of besylated Cisatracury, will be reserved for patients with P/F &lt;150.&#xD;
&#xD;
      During a 48 hrs pre-randomization period, control mechanical ventilation will be set with a&#xD;
      Tidal Volume (VT) of 6 ml / kg (for ideal weight) and a Pplat limited to 30 cm H2O;&#xD;
      inspiratory flow 50-70 l / min with end-of-breath pause of 0.2-0.5 sec, ratio I: E from 1: 1&#xD;
      to 1: 3, respiratory frequency of 20-35 steps to maintain 7.3 &lt;pH &lt;7.5. If the pH is &lt;7.30&#xD;
      the respiratory frequency will increase up to 35 / min; If the pH is&gt; 7.5, the respiratory&#xD;
      rate will be progressively reduced to the target pH range. FiO2 and The PEEP will be set&#xD;
      according to the ARDSnet table (33)&#xD;
&#xD;
      After 48 hours, the patient will be randomized through one of the following two groups:&#xD;
&#xD;
      Control Mechanical ventilation (CMV): patient's spontaneous activity will be shut done by&#xD;
      sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure&#xD;
      (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the&#xD;
      ARDSnet protocol (33).&#xD;
&#xD;
      Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and&#xD;
      sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between&#xD;
      -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the&#xD;
      pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2&#xD;
      and respiratory rate will be regulated according the ARDSnet protocol (33)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 1, 2017</start_date>
  <completion_date type="Anticipated">September 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">September 1, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary concentration of inflammation mediators (broncho-alveolar lavage: BAL)</measure>
    <time_frame>96 hours</time_frame>
    <description>Dosage of inflammatory mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systemic concentration of inflammation mediators (plasma)</measure>
    <time_frame>96 hours</time_frame>
    <description>The concentrations of the same mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist) in a sample of 10 ml of blood taken from a central venous line will be analyzed</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of ventilator-free days (VFDs) during the 28 days immediately after randomization</measure>
    <time_frame>28 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Relationship between cytokine concentration and trans-pulmonary pressure</measure>
    <time_frame>96 hours</time_frame>
    <description>End-expiratory and end-inspiratory occlusions will be performed. End-inspiratory Plateau Pressure. Pplat of the respiratory system (Pplatrs) will be the value of PAW after an end-inspiratory occlusion. End-inspiratory chest wall plateau pressure (PplatCW) will be measured as the variation in PES between end-expiratory and end-inspiratory occlusions; end-inspiratory plateau pressure of the lung (Pplatl) were estimated as Pplatrs - PplatCW</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>ARDS</condition>
  <condition>Ventilator-Induced Lung Injury</condition>
  <condition>Mechanical Ventilation Complication</condition>
  <condition>Inflammatory Response</condition>
  <arm_group>
    <arm_group_label>Pressure Support Ventilation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>after 48h of controlled ventilation the patient randomised in this arm will desedated and switched on Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol.&#xD;
assessment of inflammatory response during PSV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controlled Mechanical Ventilation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patient's spontaneous activity will be shut done by sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>assessment of inflammatory response during PSV</intervention_name>
    <description>assessment cytokines level in BAL and plasma</description>
    <arm_group_label>Controlled Mechanical Ventilation</arm_group_label>
    <arm_group_label>Pressure Support Ventilation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt; 18 years of age who:&#xD;
&#xD;
               1. Are intubated less than 24 hours since meeting the Berlin definition criteria for&#xD;
                  ARDS.&#xD;
&#xD;
               2. Have a commitment to full support;&#xD;
&#xD;
               3. Have no exclusion criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Intubation and mechanical ventilation (any form) for &gt; 24 hours;&#xD;
&#xD;
          2. Acute brain injury with Glasgow coma scale (GCS) &lt;7;&#xD;
&#xD;
          3. Body mass index &gt; 40;&#xD;
&#xD;
          4. Age &lt; 18 years;&#xD;
&#xD;
          5. Neuromuscular disease that impairs ability to ventilate without assistance;&#xD;
&#xD;
          6. Severe chronic respiratory disease;&#xD;
&#xD;
          7. Burns &gt; 40% total body surface area;&#xD;
&#xD;
          8. Malignancy or other irreversible disease or condition for which 6-month mortality is&#xD;
             estimated to be greater than 50%;&#xD;
&#xD;
          9. Allogeneic bone marrow transplant within the last 5 years;&#xD;
&#xD;
         10. Chronic respiratory condition making patient respirator dependent;&#xD;
&#xD;
         11. Patient, surrogate, or physician not committed to full support;&#xD;
&#xD;
         12. Acute myocardial infarction or acute coronary syndrome within 30 days;&#xD;
&#xD;
         13. Moribund patient: not expected to survive 24 hours;&#xD;
&#xD;
         14. No consent/inability to obtain consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>August 9, 2017</last_update_submitted>
  <last_update_submitted_qc>August 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Francesco Alessandri</investigator_full_name>
    <investigator_title>Dirigente medico I livello ( Medical Division of Anestesia andintensive care unit)</investigator_title>
  </responsible_party>
  <keyword>ARDS</keyword>
  <keyword>Ventilator-induced Lung Injury</keyword>
  <keyword>cytokines</keyword>
  <keyword>mechanical ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Ventilator-Induced Lung Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03245684
org study id: ASCOVENT
nct id: NCT03245684
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The present pilot randomized controlled clinical trial will test the hypothesis that in
      patients with ARDS, fixing ventilator settings to the conventional protective ventilatory
      strategy (VT 6 ml/kg ideal body weight and Pplat ≤ 30 cmH2O, PEEP according the PEEP/FiO2
      table), control modes of mechanical ventilation will be associated to a concentration of
      pulmonary and systemic inflammatory mediators lower than the concentration of inflammatory
      mediators observed during assisted modes of mechanical ventilation.
All patients will be treated according to the sedation protocols and standards of care.
      Sedation will be guaranteed by continuous infusion of Propofol 2-4 ml / Kg / h, Remifentanil
      0.05-0.1 mcg / Kg / min to obtain a RASS scale level of -5 of the RASS. Mio-resolution
      eventually obtained by a loading dose of 15 mg e.v. followed by a continuous infusion of 37.5
      mg / h of besylated Cisatracury, will be reserved for patients with P/F <150.

      During a 48 hrs pre-randomization period, control mechanical ventilation will be set with a
      Tidal Volume (VT) of 6 ml / kg (for ideal weight) and a Pplat limited to 30 cm H2O;
      inspiratory flow 50-70 l / min with end-of-breath pause of 0.2-0.5 sec, ratio I: E from 1: 1
      to 1: 3, respiratory frequency of 20-35 steps to maintain 7.3 <pH <7.5. If the pH is <7.30
      the respiratory frequency will increase up to 35 / min; If the pH is> 7.5, the respiratory
      rate will be progressively reduced to the target pH range. FiO2 and The PEEP will be set
      according to the ARDSnet table (33)

      After 48 hours, the patient will be randomized through one of the following two groups:

      Control Mechanical ventilation (CMV): patient's spontaneous activity will be shut done by
      sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure
      (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the
      ARDSnet protocol (33).

      Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and
      sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between
      -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the
      pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2
      and respiratory rate will be regulated according the ARDSnet protocol (33)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pulmonary concentration of inflammation mediators (broncho-alveolar lavage: BAL)
time frame: 96 hours
description: Dosage of inflammatory mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist)
measure: Systemic concentration of inflammation mediators (plasma)
time frame: 96 hours
description: The concentrations of the same mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist) in a sample of 10 ml of blood taken from a central venous line will be analyzed
measure: Number of ventilator-free days (VFDs) during the 28 days immediately after randomization
time frame: 28 days
measure: Relationship between cytokine concentration and trans-pulmonary pressure
time frame: 96 hours
description: End-expiratory and end-inspiratory occlusions will be performed. End-inspiratory Plateau Pressure. Pplat of the respiratory system (Pplatrs) will be the value of PAW after an end-inspiratory occlusion. End-inspiratory chest wall plateau pressure (PplatCW) will be measured as the variation in PES between end-expiratory and end-inspiratory occlusions; end-inspiratory plateau pressure of the lung (Pplatl) were estimated as Pplatrs - PplatCW
arm group label: Pressure Support Ventilation
arm group type: Experimental
description: after 48h of controlled ventilation the patient randomised in this arm will desedated and switched on Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol.
assessment of inflammatory response during PSV
arm group label: Controlled Mechanical Ventilation
arm group type: Active Comparator
description: patient's spontaneous activity will be shut done by sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol
intervention type: Diagnostic Test
intervention name: assessment of inflammatory response during PSV
description: assessment cytokines level in BAL and plasma
arm group label: Controlled Mechanical Ventilation
arm group label: Pressure Support Ventilation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Francesco Alessandri
investigator title: Dirigente medico I livello ( Medical Division of Anestesia andintensive care unit)
mesh term: Lung Injury
mesh term: Ventilator-Induced Lung Injury
sharing ipd: Undecided