<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/NCT03768154</url>
  </required_header>
  <id_info>
    <org_study_id>PROSE</org_study_id>
    <nct_id>NCT03768154</nct_id>
  </id_info>
  <brief_title>Prone Positioning and Spontaneous Breathing</brief_title>
  <acronym>PROSE</acronym>
  <official_title>Prone Positioning and Spontaneous Breathing: a Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Osaka University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Rebagliati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Osaka University</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>
      Spontaneous breathing during mechanical ventilation has been recommended in patients with&#xD;
      ARDS and is currently used. in part because oxygenation is better and there is a lower risk&#xD;
      of diaphragm dysfunction due to disuse. The other approach to minimizing lung injury from&#xD;
      spontaneous effort is the use of neuromuscular blockade; an early and short term (48 hours)&#xD;
      of neuromuscular blockade in patients with severe ARDS has been shown to decrease&#xD;
      inflammation and to improve survival. The investigators propose a pilot study to test the&#xD;
      feasibility and the physiological effects of allowing spontaneous breathing in the prone&#xD;
      position in patients with ARDS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The multi-center feasibility study will enroll 12 adult ARDS patients from the Intensive Care&#xD;
      Units (ICUs) in Japan and Peru. Informed consent will be obtained from the patient or legally&#xD;
      authorized substitute decision maker. Moderate-to-severe ARDS patients who are planned to&#xD;
      turn to prone positioning, based on the attending physician's decisions will be included.&#xD;
      Prior to initiating the protocol, patients will be sedated deeply with sedatives and/or&#xD;
      opioids. Ventilator settings, physiological data, esophageal pressure and diaphragm activity&#xD;
      will be recorded and physiological measurements will be collected for 5 minutes in supine&#xD;
      (Measurement 1: Supine + spontaneous effort) . Patients will be paralyzed with a continuous&#xD;
      infusion of rocuronium, and Measurement 2 (Supine + paralysis) will be recorded. The critical&#xD;
      care team in the ICU change the position from supine to prone. After waiting for at least 1&#xD;
      hour in prone positioning, Measurement 3 (Prone + paralysis) will be recorded. Continuous&#xD;
      infusion of rocuronium will be gradually decreased (and can be terminated) until spontaneous&#xD;
      breathing will be observed without reaching an excessive level. The presence of spontaneous&#xD;
      breathing will be evaluated by the negative swing of esophageal pressure, and Measurement 5&#xD;
      (Prone + spontaneous breathing) will be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 8, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Measurement 1 (Supine + spontaneous effort) , Measurement 2 (Supine + paralysis) , Measurement 3 (Prone + paralysis) , Measurement 4 (Prone + spontaneous breathing)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>spontaneous breathing</measure>
    <time_frame>Through study completion (up to 24 hours)</time_frame>
    <description>The intensity of spontaneous breathing during supine vs. prone estimated by an esophageal manometry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>inflammatory cytokines</measure>
    <time_frame>Through study completion (up to 24 hours)</time_frame>
    <description>IL-6 levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trans-pulmonary pressure</measure>
    <time_frame>Through study completion (up to 24 hours)</time_frame>
    <description>Trans-pulmonary pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>electrical activity of diaphragm</measure>
    <time_frame>Through study completion (up to 24 hours)</time_frame>
    <description>electrical activity of diaphragm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>gas exchange</measure>
    <time_frame>Through study completion (up to 24 hours)</time_frame>
    <description>gas exchange</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Critical Illness</condition>
  <condition>ARDS</condition>
  <arm_group>
    <arm_group_label>study arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>all patients will receive all four intervention in the same sequential method</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Supine + spontaneous effort</intervention_name>
    <description>without muscle paralysis in supine position</description>
    <arm_group_label>study arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Supine + paralysis</intervention_name>
    <description>administer muscle paralysis in supine position</description>
    <arm_group_label>study arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Prone + paralysis</intervention_name>
    <description>change the patient position from supine to prone with muscle paralysis</description>
    <arm_group_label>study arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Prone + spontaneous breathing</intervention_name>
    <description>cease the paralysis in supine position</description>
    <arm_group_label>study arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≧ 18 years old&#xD;
&#xD;
          -  Patients with moderate-to-severe ARDS as per the Berlin definition&#xD;
&#xD;
          -  Patients with esophageal balloon manometry&#xD;
&#xD;
          -  Patients planned to turn to prone positioning, based on the attending physician's&#xD;
             decisions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication for prone positioning, referring to a previous randomized clinical&#xD;
             trial&#xD;
&#xD;
               1. Intracranial pressure &gt;30 mm Hg or cerebral perfusion pressure &lt;60 mmHg&#xD;
&#xD;
               2. Massive hemoptysis requiring an immediate surgical or interventional radiology&#xD;
                  procedure&#xD;
&#xD;
               3. Tracheal surgery or sternotomy during the previous 15 days&#xD;
&#xD;
               4. Serious facial trauma or facial surgery during the previous 15 days&#xD;
&#xD;
               5. Cardiac pacemaker inserted in the last 2 days&#xD;
&#xD;
               6. Unstable spine, femur, or pelvic fractures&#xD;
&#xD;
          -  Major hemodynamic instability:&#xD;
&#xD;
        Mean arterial pressure lower than 60 mm Hg despite adequate fluid resuscitation and two&#xD;
        vasopressors or increase of vasopressor dose by 30% in the previous 6 hours.&#xD;
&#xD;
          -  Contraindication to EIT electrode placement Burns, chest wall bandaging limiting&#xD;
             electrode placement, pacemaker&#xD;
&#xD;
          -  Clinical judgement of the attending physician against proning and/or spontaneous&#xD;
             breathing&#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>Takeshi Yoshida, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Osaka University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Osaka University Hospital</name>
      <address>
        <city>Suita</city>
        <state>Osaka</state>
        <zip>565-0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>May 13, 2020</last_update_submitted>
  <last_update_submitted_qc>May 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>spontaneous breathing</keyword>
  <keyword>prone position</keyword>
  <keyword>muscle paralysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03768154
org study id: PROSE
nct id: NCT03768154
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Spontaneous breathing during mechanical ventilation has been recommended in patients with
      ARDS and is currently used. in part because oxygenation is better and there is a lower risk
      of diaphragm dysfunction due to disuse. The other approach to minimizing lung injury from
      spontaneous effort is the use of neuromuscular blockade; an early and short term (48 hours)
      of neuromuscular blockade in patients with severe ARDS has been shown to decrease
      inflammation and to improve survival. The investigators propose a pilot study to test the
      feasibility and the physiological effects of allowing spontaneous breathing in the prone
      position in patients with ARDS.
The multi-center feasibility study will enroll 12 adult ARDS patients from the Intensive Care
      Units (ICUs) in Japan and Peru. Informed consent will be obtained from the patient or legally
      authorized substitute decision maker. Moderate-to-severe ARDS patients who are planned to
      turn to prone positioning, based on the attending physician's decisions will be included.
      Prior to initiating the protocol, patients will be sedated deeply with sedatives and/or
      opioids. Ventilator settings, physiological data, esophageal pressure and diaphragm activity
      will be recorded and physiological measurements will be collected for 5 minutes in supine
      (Measurement 1: Supine + spontaneous effort) . Patients will be paralyzed with a continuous
      infusion of rocuronium, and Measurement 2 (Supine + paralysis) will be recorded. The critical
      care team in the ICU change the position from supine to prone. After waiting for at least 1
      hour in prone positioning, Measurement 3 (Prone + paralysis) will be recorded. Continuous
      infusion of rocuronium will be gradually decreased (and can be terminated) until spontaneous
      breathing will be observed without reaching an excessive level. The presence of spontaneous
      breathing will be evaluated by the negative swing of esophageal pressure, and Measurement 5
      (Prone + spontaneous breathing) will be recorded.
intervention model: Sequential Assignment
intervention model description: Measurement 1 (Supine + spontaneous effort) , Measurement 2 (Supine + paralysis) , Measurement 3 (Prone + paralysis) , Measurement 4 (Prone + spontaneous breathing)
primary purpose: Treatment
masking: None (Open Label)
measure: spontaneous breathing
time frame: Through study completion (up to 24 hours)
description: The intensity of spontaneous breathing during supine vs. prone estimated by an esophageal manometry
measure: inflammatory cytokines
time frame: Through study completion (up to 24 hours)
description: IL-6 levels
measure: Trans-pulmonary pressure
time frame: Through study completion (up to 24 hours)
description: Trans-pulmonary pressure
measure: electrical activity of diaphragm
time frame: Through study completion (up to 24 hours)
description: electrical activity of diaphragm
measure: gas exchange
time frame: Through study completion (up to 24 hours)
description: gas exchange
arm group label: study arm
arm group type: Experimental
description: all patients will receive all four intervention in the same sequential method
intervention type: Procedure
intervention name: Supine + spontaneous effort
description: without muscle paralysis in supine position
arm group label: study arm
intervention type: Procedure
intervention name: Supine + paralysis
description: administer muscle paralysis in supine position
arm group label: study arm
intervention type: Procedure
intervention name: Prone + paralysis
description: change the patient position from supine to prone with muscle paralysis
arm group label: study arm
intervention type: Procedure
intervention name: Prone + spontaneous breathing
description: cease the paralysis in supine position
arm group label: study arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Takeshi Yoshida, PhD
role: Principal Investigator
affiliation: Osaka University
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Critical Illness
sharing ipd: No