<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/NCT01730794</url>
  </required_header>
  <id_info>
    <org_study_id>2012P002419</org_study_id>
    <nct_id>NCT01730794</nct_id>
  </id_info>
  <brief_title>Neurally Adjusted Ventilatory Assist (NAVA) Study in Adults With Acute Respiratory Failure</brief_title>
  <official_title>A Comparative, Multicenter, Randomized, Controlled Study of Neurally Adjusted Ventilatory Assist (NAVA) vs. Conventional Lung Protective Ventilation in Patients With Acute Respiratory Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dr. Negrin University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare a specific mode of artificial ventilation (help from&#xD;
      a breathing machine) with other modes. This specific mode is called Neurally Adjusted&#xD;
      Ventilatory Assist (NAVA) and is different from other modes as it uses direct signals from&#xD;
      the diaphragm (breathing muscle) to help patients breathe. The investigators believe that&#xD;
      using these signals, NAVA can determine the exact timing for patients' spontaneous breathing&#xD;
      effort and delivers the artificial breath at the same time (in synchrony) with their own&#xD;
      breath. Other modes (breathing methods) may cause asynchrony between the patient and the&#xD;
      ventilator while delivering artificial breaths because of the way they operate. Asyncrony&#xD;
      between patient and ventilator is a risk factor for increasing the length of artificial&#xD;
      ventilation and number of related complications. The investigators would like to find out if&#xD;
      NAVA performs better in establishing synchrony between patient and ventilator and as a result&#xD;
      decreasing time for artificial ventilation and increasing better outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Goal To compare the ability of NAVA vs. conventional lung protective ventilation in a&#xD;
      multicenter, unblinded, randomized, controlled fashion to provide invasive ventilatory&#xD;
      support during acute respiratory failure in adults who are expected to require ventilatory&#xD;
      support for greater than 72 hours.&#xD;
&#xD;
      Hypothesis It is hypothesized that the use of NAVA compared to conventional lung protective&#xD;
      ventilation will result in a decrease in the number of days of mechanical ventilation. It is&#xD;
      further hypothesized that NAVA compared to conventional lung protective ventilation will&#xD;
      result in a decrease in the length of weaning, the length of ICU and hospital stay, and&#xD;
      mortality.&#xD;
&#xD;
      Primary Outcome&#xD;
&#xD;
      • Number of invasive ventilator free days.&#xD;
&#xD;
      Secondary Outcome&#xD;
&#xD;
        -  Mortality&#xD;
&#xD;
        -  Length of Invasive Ventilation in survivors&#xD;
&#xD;
        -  Length of ICU and hospital stay&#xD;
&#xD;
        -  Incidence of barotrauma (defined as the presence of any extra-pulmonary air that was not&#xD;
           present at study enrollment).&#xD;
&#xD;
        -  Ventilator associated pneumonia (development of a pneumonia 48 hrs after entry into the&#xD;
           study).&#xD;
&#xD;
        -  Development of ARDS (after enrollment into the study; defined as a rapid onset, a&#xD;
           P/F&lt;200 mmHg, and bilateral pulmonary infiltrates that are not of cardiac origin).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 28, 2014</start_date>
  <completion_date type="Actual">January 22, 2020</completion_date>
  <primary_completion_date type="Actual">January 22, 2020</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>Number of invasive ventilator free days.</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days without mechanical ventilation, within the first 28 days of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total length of mechanical ventilation in survivors (invasive plus noninvasive)</measure>
    <time_frame>90 days</time_frame>
    <description>Total number of days of mechanical ventilation in ICU survivors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU and hospital Mortality</measure>
    <time_frame>90 days</time_frame>
    <description>Mortality during patient stay in the ICU and after being discharged from ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of barotrauma</measure>
    <time_frame>60 Days</time_frame>
    <description>Number of diagnosed pneumothorax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator associated pneumonia</measure>
    <time_frame>60 Days</time_frame>
    <description>Number of diagnosed Ventilator Associated Pneumonia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of Acute respiratory distress syndrome (ARDS)</measure>
    <time_frame>60 Days</time_frame>
    <description>Number of patients developing ARDS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ICU stay</measure>
    <time_frame>90 Days</time_frame>
    <description>Total number of days of ICU stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>90 Days</time_frame>
    <description>Total number of days of Hospital stay.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">306</enrollment>
  <condition>Acute Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>Conventional Lung Protective Ventilation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In this group, patients will be ventilated in either volume A/C, pressure A/C, pressure support, pressure regulated volume control or volume support based on the discretion of the medical team with TV 4-8 ml/kg PBW range and PP or pressure (control or support) level &lt;30 cmH2O.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NAVA Ventilation Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In the NAVA group, NAVA level will be set initially at zero, then the maximum Edi will be determined as the average level over the next 3 to 5 breaths without ventilatory support or PEEP. The actual NAVA level will then be titrated by the clinician to achieve the following: 1) an Edi equal to approximately 50% of the maximum Edi, 2) an average tidal volume of between 4 to 8 ml/kg predicted body weight (PBW), and 3) an average respiratory rate between about 15 and 40 per minute. In addition, the trigger sensitivity should be set as sensitive as possible without causing auto-triggering and the maximum pressure limit in NAVA should be set at 40 cm H2O.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>NAVA ventilation</intervention_name>
    <description>Neurally adjusted ventilatory assist</description>
    <arm_group_label>NAVA Ventilation Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional Lung Protective Ventilation</intervention_name>
    <description>conventional protective mechanical ventilation</description>
    <arm_group_label>Conventional Lung Protective Ventilation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than or equal to 18 years&#xD;
&#xD;
          -  Hypoxemic or hypercapnic acute respiratory failure&#xD;
&#xD;
          -  Intubation and mechanical ventilation&#xD;
&#xD;
          -  Anticipated mechanical ventilation equal or longer than 72 hrs&#xD;
&#xD;
          -  Mechanically ventilated less or equal to 5 days&#xD;
&#xD;
          -  Able to spontaneously trigger the ventilator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  moderate-to-severe acute respiratory distress syndrome&#xD;
&#xD;
          -  Post-operative patient's normally requiring a short course of mechanical ventilation&#xD;
             (for example most cardiac surgical patients)&#xD;
&#xD;
          -  Unable to spontaneously breathe&#xD;
&#xD;
          -  Need to provide controlled ventilation&#xD;
&#xD;
          -  Poor short term prognosis (defined as a high risk of death in the next 3 months)&#xD;
&#xD;
          -  Neuromuscular or neurologic disease&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  Patients with major esophageal, gastric and oral surgery&#xD;
&#xD;
          -  Acute brain injury or elevated intracranial pressure (&gt; 18 mmHg)&#xD;
&#xD;
          -  Severe cardiac disease: New York Heart Association class 3 or 4 or acute coronary&#xD;
             syndrome or persistent ventricular tachyarrhythmias.&#xD;
&#xD;
          -  Pregnancy, must be confirmed by laboratory analysis.&#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>Robert M Kacmarek, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jesus Villar, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nanjing Zhongda Hospital Southeast University</name>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario NS de Candelaria</name>
      <address>
        <city>Santa Cruz De Tenerife</city>
        <state>Tenerife</state>
        <zip>38010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital NS del Prado</name>
      <address>
        <city>Talavera De La Reina</city>
        <state>Toledo</state>
        <zip>45600</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Albacete</name>
      <address>
        <city>Albacete</city>
        <zip>02006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Luz</name>
      <address>
        <city>Cuenca</city>
        <zip>16002</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Fundación Jiménez Díaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Morales Meseguer</name>
      <address>
        <city>Murcia</city>
        <zip>30008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de Arrixaca</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Salud</name>
      <address>
        <city>Toledo</city>
        <zip>45004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico de Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Rio Hortega</name>
      <address>
        <city>Valladolid</city>
        <zip>47012</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Txagorritxu</name>
      <address>
        <city>Vitoria</city>
        <state>Álava</state>
        <zip>01007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>January 23, 2020</last_update_submitted>
  <last_update_submitted_qc>January 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Robert M. Kacmarek</investigator_full_name>
    <investigator_title>Professor of Anesthesia, Director of Respiratory Care Services</investigator_title>
  </responsible_party>
  <keyword>Acute Respiratory Failure</keyword>
  <keyword>Mechanical Ventilation</keyword>
  <keyword>NAVA</keyword>
  <keyword>Lung protective ventilation</keyword>
  <keyword>invasive ventilation</keyword>
  <keyword>noninvasive ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</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/NCT01730794
org study id: 2012P002419
nct id: NCT01730794
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to compare a specific mode of artificial ventilation (help from
      a breathing machine) with other modes. This specific mode is called Neurally Adjusted
      Ventilatory Assist (NAVA) and is different from other modes as it uses direct signals from
      the diaphragm (breathing muscle) to help patients breathe. The investigators believe that
      using these signals, NAVA can determine the exact timing for patients' spontaneous breathing
      effort and delivers the artificial breath at the same time (in synchrony) with their own
      breath. Other modes (breathing methods) may cause asynchrony between the patient and the
      ventilator while delivering artificial breaths because of the way they operate. Asyncrony
      between patient and ventilator is a risk factor for increasing the length of artificial
      ventilation and number of related complications. The investigators would like to find out if
      NAVA performs better in establishing synchrony between patient and ventilator and as a result
      decreasing time for artificial ventilation and increasing better outcomes.
Study Goal To compare the ability of NAVA vs. conventional lung protective ventilation in a
      multicenter, unblinded, randomized, controlled fashion to provide invasive ventilatory
      support during acute respiratory failure in adults who are expected to require ventilatory
      support for greater than 72 hours.

      Hypothesis It is hypothesized that the use of NAVA compared to conventional lung protective
      ventilation will result in a decrease in the number of days of mechanical ventilation. It is
      further hypothesized that NAVA compared to conventional lung protective ventilation will
      result in a decrease in the length of weaning, the length of ICU and hospital stay, and
      mortality.

      Primary Outcome

      • Number of invasive ventilator free days.

      Secondary Outcome

        -  Mortality

        -  Length of Invasive Ventilation in survivors

        -  Length of ICU and hospital stay

        -  Incidence of barotrauma (defined as the presence of any extra-pulmonary air that was not
           present at study enrollment).

        -  Ventilator associated pneumonia (development of a pneumonia 48 hrs after entry into the
           study).

        -  Development of ARDS (after enrollment into the study; defined as a rapid onset, a
           P/F<200 mmHg, and bilateral pulmonary infiltrates that are not of cardiac origin).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of invasive ventilator free days.
time frame: 28 days
description: Number of days without mechanical ventilation, within the first 28 days of the study.
measure: Total length of mechanical ventilation in survivors (invasive plus noninvasive)
time frame: 90 days
description: Total number of days of mechanical ventilation in ICU survivors.
measure: ICU and hospital Mortality
time frame: 90 days
description: Mortality during patient stay in the ICU and after being discharged from ICU
measure: Incidence of barotrauma
time frame: 60 Days
description: Number of diagnosed pneumothorax
measure: Ventilator associated pneumonia
time frame: 60 Days
description: Number of diagnosed Ventilator Associated Pneumonia
measure: Development of Acute respiratory distress syndrome (ARDS)
time frame: 60 Days
description: Number of patients developing ARDS
measure: Length of ICU stay
time frame: 90 Days
description: Total number of days of ICU stay.
measure: Length of hospital stay
time frame: 90 Days
description: Total number of days of Hospital stay.
arm group label: Conventional Lung Protective Ventilation
arm group type: Other
description: In this group, patients will be ventilated in either volume A/C, pressure A/C, pressure support, pressure regulated volume control or volume support based on the discretion of the medical team with TV 4-8 ml/kg PBW range and PP or pressure (control or support) level <30 cmH2O.
arm group label: NAVA Ventilation Group
arm group type: Other
description: In the NAVA group, NAVA level will be set initially at zero, then the maximum Edi will be determined as the average level over the next 3 to 5 breaths without ventilatory support or PEEP. The actual NAVA level will then be titrated by the clinician to achieve the following: 1) an Edi equal to approximately 50% of the maximum Edi, 2) an average tidal volume of between 4 to 8 ml/kg predicted body weight (PBW), and 3) an average respiratory rate between about 15 and 40 per minute. In addition, the trigger sensitivity should be set as sensitive as possible without causing auto-triggering and the maximum pressure limit in NAVA should be set at 40 cm H2O.
intervention type: Other
intervention name: NAVA ventilation
description: Neurally adjusted ventilatory assist
arm group label: NAVA Ventilation Group
intervention type: Other
intervention name: Conventional Lung Protective Ventilation
description: conventional protective mechanical ventilation
arm group label: Conventional Lung Protective Ventilation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert M Kacmarek, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Jesus Villar, MD, PhD
role: Principal Investigator
affiliation: Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
country: Spain
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Robert M. Kacmarek
investigator title: Professor of Anesthesia, Director of Respiratory Care Services
mesh term: Respiratory Insufficiency
mesh term: Respiratory Distress Syndrome