<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/NCT03271671</url>
  </required_header>
  <id_info>
    <org_study_id>TRB2447/1/7/17</org_study_id>
    <nct_id>NCT03271671</nct_id>
  </id_info>
  <brief_title>Pressure Support Ventilation (PSV) Versus Neurally Adjusted Ventilator Assist (NAVA) During Acute Respiratory Failure (ARF)</brief_title>
  <official_title>A Randomized Controlled Trial Comparing Non-invasive Ventilation (NIV) With Pressure Support Ventilation (PSV) Versus Neurally Adjusted Ventilator Assist (NAVA) During Acute Respiratory Failure (ARF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Acute respiratory failure (ARF) is a life-threatening emergency which occurs due to impaired&#xD;
      gas exchange. In the US, the number of hospitalisations owing to acute respiratory failure&#xD;
      was 1,917,910 in the year 2009.(1) The incidence of ARF requiring hospitalization was 137.1&#xD;
      per 100,000 population.(2) In ARF due to chronic obstructive pulmonary disease (COPD) and&#xD;
      cardiogenic pulmonary edema, non-invasive ventilation (NIV) has been shown to be beneficial.&#xD;
      NIV also has several advantages over invasive mechanical ventilation. These include,&#xD;
      avoidance of endotracheal intubation and its attendant complications like airway injury,&#xD;
      nosocomial infections, and possibly shorter duration of intensive care unit (ICU) stay.(3, 4)&#xD;
      The success of NIV depends on several factors like the etiology of the respiratory failure,&#xD;
      careful monitoring by the treating physician, and also adequate cooperation of patient.&#xD;
      Better synchrony of the patient's spontaneous breaths with the ventilator-delivered breaths&#xD;
      may lead to better patient cooperation and thereby, better clinical outcomes.&#xD;
      Patient-ventilator asynchrony (PVA) leads to dyspnea, increased work of breathing, and&#xD;
      prolonged duration of mechanical ventilation.(5) Pressure support ventilation (PSV) is one of&#xD;
      the commonest mode used during NIV. In a prospective multicenter observational study, severe&#xD;
      asynchrony (defined as an asynchrony index of &gt;10 %) was seen in 43% of patients of patients&#xD;
      with ARF ventilated by NIV with the conventional PSV mode.(6) Neurally adjusted ventilator&#xD;
      assist (NAVA) is new mode of ventilation which utilizes the electrical activity of the&#xD;
      diaphragm to deliver the breath.(7) During NAVA, breath is delivered when the patient's&#xD;
      diaphragm starts contracting. Further, the amount of pressure support given during the breath&#xD;
      is proportional to the strength of the electrical signal from the diaphragm. Finally, NAVA&#xD;
      also terminates the breath when the electrical activity of the diaphragm wanes. NAVA has been&#xD;
      shown to avoid over-assistance, decrease intrinsic positive end-expiratory pressure (PEEP),&#xD;
      and minimize wasted efforts.(8) Hence, NAVA may play a major role in improving&#xD;
      patient-ventilator synchrony.&#xD;
&#xD;
      In a pooled analysis of studies comparing NAVA with PSV during NIV, it was shown that the use&#xD;
      of NAVA significantly improved patient-ventilator synchrony.(9) However, so far, no clinical&#xD;
      trial has demonstrated that this improvement in synchrony translates into better clinical&#xD;
      outcomes. In this randomized controlled clinical trial, we intend to compare the rates of NIV&#xD;
      failure and mortality between NAVA and PSV in subjects with acute respiratory failure managed&#xD;
      with NIV.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      NIV is mode of ventilation wherein positive pressure ventilation is delivered by non-invasive&#xD;
      interface like nasal mask, face mask, nasal plugs or helmet avoiding invasive interface by&#xD;
      endotracheal intubation or by tracheostomy. In 1980s NIV by mask was used with success in&#xD;
      patients of obstructive sleep apnea and later on in neuromuscular respiratory failure. Use of&#xD;
      NIV has increased subsequently over next 20 years with overall first line NIV being used upto&#xD;
      23% (10) NIV is definitely useful as first line of management in COPD exacerbation,&#xD;
      cardiogenic pulmonary edema, post extubation respiratory failure and is also worth trial with&#xD;
      conflicting data in cases of acute hypoxemic respiratory failure due to pneumonia, ARDS.&#xD;
&#xD;
      In cases of acute exacerbation of COPD, NIV improves clinical outcomes.(11-13) In a&#xD;
      metaanalysis by Ram FS et al which included 14 RCT and 758 patients which showed decreased&#xD;
      mortality(11 vs 21%), intubation rate(16 vs 33%) and treatment failure(20 vs 42%)(12).&#xD;
      Similarly, there is high quality evidence supporting use in cardiogenic pulmonary edema&#xD;
      showing to improve respiratory parameters and decrease intubation rates (14-17). A&#xD;
      meta-analysis of 32 studies including 2916 patients in 2013 by Vital FM et al showed that NIV&#xD;
      reduces in hospital mortality compared to standard medical care(RR 0.66, 95% CI 0.48 -&#xD;
      0.89)(14) NAVA as mode of ventilation was developed after initial landmark study &quot;neural&#xD;
      control of mechanical ventilation in respiratory failure&quot; was published in 1998 by&#xD;
      Sinderby(7). It was later on introduced on the servo-i ventilator in 2007. NAVA is a kind of&#xD;
      pressure assist ventilation using electrical activity of diaphragm and thus the neural output&#xD;
      to initiate the breath, regulate the assist level and cycle off the breath.&#xD;
&#xD;
      In study by Piquilloud et al of 13 patients which compared NAVA with PSV during NIV there was&#xD;
      significant difference in asynchronies. Trigger delay (Td) was reduced with NAVA to 35 ms&#xD;
      (IQR 31-53 ms) versus 181 ms (122 - 208 ms). Also, there were no premature or delayed&#xD;
      cycling, ineffective efforts in the NAVA group. Asynchrony index (AI) with NAVA was 4.9% (2.2&#xD;
      - 10.5%) compared to 15.8% (5.5 - 49.6%) with PSV (20)In a recent meta-analysis comparing PSV&#xD;
      with NAVA during NIV by Inderpaul et al which included 9 studies with 96 subjects including&#xD;
      both adult and paediatric patients showed that asynchronies were more in PSV than in NAVA in&#xD;
      both adult and paediatric studies. The overall pooled mean difference of asynchrony index was&#xD;
      28.02(95% CI, 11.61 - 44.42). also the risk of severe asynchrony was 3.4 % times higher in&#xD;
      PSV compared to NAVA group.(9) NAVA mode of ventilation in previous studies has shown to&#xD;
      decrease asynchrony with ventilator, mainly reducing ineffective efforts, cycling delays.&#xD;
      Ineffective efforts may occur due to presence of intrinsic PEEP which in turn is more common&#xD;
      during prolonged insufflations and at high levels of assist. Ineffective efforts may also&#xD;
      occur with weak inspiratory efforts which may occur during states of high respiratory drive.&#xD;
      NAVA uses electrical activity of diaphragm to trigger a breath and there is marked difference&#xD;
      in improving synchrony with studies reporting no wasted efforts when compared to PSV mode. In&#xD;
      a study by Vignaux et al showed that during conventional NIV, 40 % of the patients experience&#xD;
      asynchrony and the rate of asynchrony correlated with leakage(6). In NAVA mode of ventilation&#xD;
      assistance is delivered based upon the neural trigger and hence is not affected by leaks.&#xD;
&#xD;
      In a pooled analysis of studies comparing NAVA with PSV during NIV, it was shown that the use&#xD;
      of NAVA significantly improved patient-ventilator synchrony.(9) However, so far, no clinical&#xD;
      trial has demonstrated that this improvement in synchrony translates into better clinical&#xD;
      outcomes. In this randomized controlled clinical trial, we intend to compare the rates of NIV&#xD;
      failure and mortality between NAVA and PSV in subjects with acute respiratory failure managed&#xD;
      with NIV.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">March 31, 2019</completion_date>
  <primary_completion_date type="Actual">March 15, 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>
    <intervention_model_description>Randomized controlled trial comparing two modes of non invasive ventilation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rates of NIV failures</measure>
    <time_frame>28 days</time_frame>
    <description>NIV will be deemed to have failed if the patient gets intubated or is reinitiated on NIV within 48 hours of discontinuation of NIV</description>
  </primary_outcome>
  <primary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>28 days</time_frame>
    <description>28-day mortality including ICU and hospital deaths will be assessed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to successful weaning</measure>
    <time_frame>28 days</time_frame>
    <description>Time to successful weaning will be defined as the duration between initiation of NIV and successful weaning from NIV.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to NIV failure</measure>
    <time_frame>28 days</time_frame>
    <description>Time to NIV failure will be calculated as the duration between initiation of NIV and the event which lead to NIV failure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total duration of mechanical ventilation (both non-invasive and invasive)</measure>
    <time_frame>28 days</time_frame>
    <description>Total duration of mechanical ventilation will be calculated as the total duration spent on NIV and IMV by the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ICU and hospital stay</measure>
    <time_frame>28 days</time_frame>
    <description>The length of ICU and hospital stay of the patient will also be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's level of comfort during NIV using VAS</measure>
    <time_frame>28 days</time_frame>
    <description>The patient's level of comfort while undergoing NIV will be assessed using a similar VAS. These assessments will be made every day till day 5 or till the patient is weaned off NIV, whichever is earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physician's level of comfort while using the assigned NIV strategy using VAS</measure>
    <time_frame>28 days</time_frame>
    <description>The physician's level of comfort while using the two different modes of NIV will be assessed using a visual analogue scale (VAS). The assessment will be obtained from the treating physician at each shift.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>PSV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pressure support ventilation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NAVA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neurally adjusted ventilator assist</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>NAVA during Non invasive ventilation</intervention_name>
    <description>NIV during respiratory failure</description>
    <arm_group_label>NAVA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PSV during Non invasive ventilation</intervention_name>
    <description>PSV during respiratory failure</description>
    <arm_group_label>PSV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Respiratory rate &gt;30 per minute&#xD;
&#xD;
          2. Arterial blood gas analysis showing a PaCO2 &gt;45 mmHg and pH &lt;7.35&#xD;
&#xD;
          3. PaO2/FiO2 ratio &lt; 300&#xD;
&#xD;
          4. Use of accessory muscles of respiration or paradoxical respiration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt;18 years or &gt;75 years&#xD;
&#xD;
          2. Pregnancy&#xD;
&#xD;
          3. PaO2/FiO2 ratio ≤100&#xD;
&#xD;
          4. Hypotension (systolic blood pressure &lt;90 mmHg)&#xD;
&#xD;
          5. Severe impairment of consciousness (Glasgow coma scale score &lt;8)&#xD;
&#xD;
          6. Inability to clear respiratory secretions (Airway care score [ACS] ≥12)(27)&#xD;
&#xD;
          7. Abnormalities that preclude proper fit of the NIV interface (agitated or uncooperative&#xD;
             patient, facial trauma or burns, facial surgery, or facial anatomical abnormality)&#xD;
&#xD;
          8. Subjects who have an artificial airway like tracheostomy tube or T-tube&#xD;
&#xD;
          9. Contraindications for insertion of naso-/orogastric feeding tube (facial/nasal trauma,&#xD;
             recent upper airway surgery, esophageal surgery, esophageal varices, upper&#xD;
             gastrointestinal bleeding)&#xD;
&#xD;
         10. More than two organ failures&#xD;
&#xD;
         11. Unwillingness to undergo placement of nasogastric catheter&#xD;
&#xD;
         12. Known phrenic nerve lesions&#xD;
&#xD;
         13. Suspected diaphragmatic weakness&#xD;
&#xD;
         14. Patient already on home NIV therapy for chronic respiratory failure&#xD;
&#xD;
         15. Application of NIV for more than one hour for the current illness&#xD;
&#xD;
         16. Failure to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Inderpaul S Sehgal, MD,DM</last_name>
    <role>Principal Investigator</role>
    <affiliation>PGIMER,Chandigarh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Respiratory ICU, Post Graduate Institue of Medical Education and Research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <reference>
    <citation>Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Steingrub JS, Lagu T, Lindenauer PK. Epidemiology and outcomes of acute respiratory failure in the United States, 2001 to 2009: a national survey. J Hosp Med. 2013 Feb;8(2):76-82. doi: 10.1002/jhm.2004. Epub 2013 Jan 18.</citation>
    <PMID>23335231</PMID>
  </reference>
  <reference>
    <citation>Behrendt CE. Acute respiratory failure in the United States: incidence and 31-day survival. Chest. 2000 Oct;118(4):1100-5. doi: 10.1378/chest.118.4.1100.</citation>
    <PMID>11035684</PMID>
  </reference>
  <reference>
    <citation>Peter JV, Moran JL, Phillips-Hughes J, Warn D. Noninvasive ventilation in acute respiratory failure--a meta-analysis update. Crit Care Med. 2002 Mar;30(3):555-62. doi: 10.1097/00003246-200203000-00010.</citation>
    <PMID>11990914</PMID>
  </reference>
  <reference>
    <citation>Girou E, Schortgen F, Delclaux C, Brun-Buisson C, Blot F, Lefort Y, Lemaire F, Brochard L. Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients. JAMA. 2000 Nov 8;284(18):2361-7. doi: 10.1001/jama.284.18.2361.</citation>
    <PMID>11066187</PMID>
  </reference>
  <reference>
    <citation>Georgopoulos D, Prinianakis G, Kondili E. Bedside waveforms interpretation as a tool to identify patient-ventilator asynchronies. Intensive Care Med. 2006 Jan;32(1):34-47. doi: 10.1007/s00134-005-2828-5. Epub 2005 Nov 9.</citation>
    <PMID>16283171</PMID>
  </reference>
  <reference>
    <citation>Vignaux L, Vargas F, Roeseler J, Tassaux D, Thille AW, Kossowsky MP, Brochard L, Jolliet P. Patient-ventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study. Intensive Care Med. 2009 May;35(5):840-6. doi: 10.1007/s00134-009-1416-5. Epub 2009 Jan 29.</citation>
    <PMID>19183949</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>April 9, 2019</last_update_submitted>
  <last_update_submitted_qc>April 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Inderpaul singh</investigator_full_name>
    <investigator_title>Assistant Professor, Department of Pulmonary Medicine</investigator_title>
  </responsible_party>
  <keyword>neurally adjusted ventilator assist</keyword>
  <keyword>Pressure support ventilation</keyword>
  <keyword>non invasive ventilation</keyword>
  <keyword>niv</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Complete protocol and individual patient data after publication of results</ipd_description>
  </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/NCT03271671
org study id: TRB2447/1/7/17
nct id: NCT03271671
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Acute respiratory failure (ARF) is a life-threatening emergency which occurs due to impaired
      gas exchange. In the US, the number of hospitalisations owing to acute respiratory failure
      was 1,917,910 in the year 2009.(1) The incidence of ARF requiring hospitalization was 137.1
      per 100,000 population.(2) In ARF due to chronic obstructive pulmonary disease (COPD) and
      cardiogenic pulmonary edema, non-invasive ventilation (NIV) has been shown to be beneficial.
      NIV also has several advantages over invasive mechanical ventilation. These include,
      avoidance of endotracheal intubation and its attendant complications like airway injury,
      nosocomial infections, and possibly shorter duration of intensive care unit (ICU) stay.(3, 4)
      The success of NIV depends on several factors like the etiology of the respiratory failure,
      careful monitoring by the treating physician, and also adequate cooperation of patient.
      Better synchrony of the patient's spontaneous breaths with the ventilator-delivered breaths
      may lead to better patient cooperation and thereby, better clinical outcomes.
      Patient-ventilator asynchrony (PVA) leads to dyspnea, increased work of breathing, and
      prolonged duration of mechanical ventilation.(5) Pressure support ventilation (PSV) is one of
      the commonest mode used during NIV. In a prospective multicenter observational study, severe
      asynchrony (defined as an asynchrony index of >10 %) was seen in 43% of patients of patients
      with ARF ventilated by NIV with the conventional PSV mode.(6) Neurally adjusted ventilator
      assist (NAVA) is new mode of ventilation which utilizes the electrical activity of the
      diaphragm to deliver the breath.(7) During NAVA, breath is delivered when the patient's
      diaphragm starts contracting. Further, the amount of pressure support given during the breath
      is proportional to the strength of the electrical signal from the diaphragm. Finally, NAVA
      also terminates the breath when the electrical activity of the diaphragm wanes. NAVA has been
      shown to avoid over-assistance, decrease intrinsic positive end-expiratory pressure (PEEP),
      and minimize wasted efforts.(8) Hence, NAVA may play a major role in improving
      patient-ventilator synchrony.

      In a pooled analysis of studies comparing NAVA with PSV during NIV, it was shown that the use
      of NAVA significantly improved patient-ventilator synchrony.(9) However, so far, no clinical
      trial has demonstrated that this improvement in synchrony translates into better clinical
      outcomes. In this randomized controlled clinical trial, we intend to compare the rates of NIV
      failure and mortality between NAVA and PSV in subjects with acute respiratory failure managed
      with NIV.
NIV is mode of ventilation wherein positive pressure ventilation is delivered by non-invasive
      interface like nasal mask, face mask, nasal plugs or helmet avoiding invasive interface by
      endotracheal intubation or by tracheostomy. In 1980s NIV by mask was used with success in
      patients of obstructive sleep apnea and later on in neuromuscular respiratory failure. Use of
      NIV has increased subsequently over next 20 years with overall first line NIV being used upto
      23% (10) NIV is definitely useful as first line of management in COPD exacerbation,
      cardiogenic pulmonary edema, post extubation respiratory failure and is also worth trial with
      conflicting data in cases of acute hypoxemic respiratory failure due to pneumonia, ARDS.

      In cases of acute exacerbation of COPD, NIV improves clinical outcomes.(11-13) In a
      metaanalysis by Ram FS et al which included 14 RCT and 758 patients which showed decreased
      mortality(11 vs 21%), intubation rate(16 vs 33%) and treatment failure(20 vs 42%)(12).
      Similarly, there is high quality evidence supporting use in cardiogenic pulmonary edema
      showing to improve respiratory parameters and decrease intubation rates (14-17). A
      meta-analysis of 32 studies including 2916 patients in 2013 by Vital FM et al showed that NIV
      reduces in hospital mortality compared to standard medical care(RR 0.66, 95% CI 0.48 -
      0.89)(14) NAVA as mode of ventilation was developed after initial landmark study "neural
      control of mechanical ventilation in respiratory failure" was published in 1998 by
      Sinderby(7). It was later on introduced on the servo-i ventilator in 2007. NAVA is a kind of
      pressure assist ventilation using electrical activity of diaphragm and thus the neural output
      to initiate the breath, regulate the assist level and cycle off the breath.

      In study by Piquilloud et al of 13 patients which compared NAVA with PSV during NIV there was
      significant difference in asynchronies. Trigger delay (Td) was reduced with NAVA to 35 ms
      (IQR 31-53 ms) versus 181 ms (122 - 208 ms). Also, there were no premature or delayed
      cycling, ineffective efforts in the NAVA group. Asynchrony index (AI) with NAVA was 4.9% (2.2
      - 10.5%) compared to 15.8% (5.5 - 49.6%) with PSV (20)In a recent meta-analysis comparing PSV
      with NAVA during NIV by Inderpaul et al which included 9 studies with 96 subjects including
      both adult and paediatric patients showed that asynchronies were more in PSV than in NAVA in
      both adult and paediatric studies. The overall pooled mean difference of asynchrony index was
      28.02(95% CI, 11.61 - 44.42). also the risk of severe asynchrony was 3.4 % times higher in
      PSV compared to NAVA group.(9) NAVA mode of ventilation in previous studies has shown to
      decrease asynchrony with ventilator, mainly reducing ineffective efforts, cycling delays.
      Ineffective efforts may occur due to presence of intrinsic PEEP which in turn is more common
      during prolonged insufflations and at high levels of assist. Ineffective efforts may also
      occur with weak inspiratory efforts which may occur during states of high respiratory drive.
      NAVA uses electrical activity of diaphragm to trigger a breath and there is marked difference
      in improving synchrony with studies reporting no wasted efforts when compared to PSV mode. In
      a study by Vignaux et al showed that during conventional NIV, 40 % of the patients experience
      asynchrony and the rate of asynchrony correlated with leakage(6). In NAVA mode of ventilation
      assistance is delivered based upon the neural trigger and hence is not affected by leaks.

      In a pooled analysis of studies comparing NAVA with PSV during NIV, it was shown that the use
      of NAVA significantly improved patient-ventilator synchrony.(9) However, so far, no clinical
      trial has demonstrated that this improvement in synchrony translates into better clinical
      outcomes. In this randomized controlled clinical trial, we intend to compare the rates of NIV
      failure and mortality between NAVA and PSV in subjects with acute respiratory failure managed
      with NIV.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled trial comparing two modes of non invasive ventilation
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Rates of NIV failures
time frame: 28 days
description: NIV will be deemed to have failed if the patient gets intubated or is reinitiated on NIV within 48 hours of discontinuation of NIV
measure: 28-day mortality
time frame: 28 days
description: 28-day mortality including ICU and hospital deaths will be assessed
measure: Time to successful weaning
time frame: 28 days
description: Time to successful weaning will be defined as the duration between initiation of NIV and successful weaning from NIV.
measure: Time to NIV failure
time frame: 28 days
description: Time to NIV failure will be calculated as the duration between initiation of NIV and the event which lead to NIV failure.
measure: Total duration of mechanical ventilation (both non-invasive and invasive)
time frame: 28 days
description: Total duration of mechanical ventilation will be calculated as the total duration spent on NIV and IMV by the patient.
measure: Length of ICU and hospital stay
time frame: 28 days
description: The length of ICU and hospital stay of the patient will also be assessed.
measure: Patient's level of comfort during NIV using VAS
time frame: 28 days
description: The patient's level of comfort while undergoing NIV will be assessed using a similar VAS. These assessments will be made every day till day 5 or till the patient is weaned off NIV, whichever is earlier.
measure: Physician's level of comfort while using the assigned NIV strategy using VAS
time frame: 28 days
description: The physician's level of comfort while using the two different modes of NIV will be assessed using a visual analogue scale (VAS). The assessment will be obtained from the treating physician at each shift.
arm group label: PSV
arm group type: Active Comparator
description: Pressure support ventilation
arm group label: NAVA
arm group type: Experimental
description: Neurally adjusted ventilator assist
intervention type: Other
intervention name: NAVA during Non invasive ventilation
description: NIV during respiratory failure
arm group label: NAVA
intervention type: Other
intervention name: PSV during Non invasive ventilation
description: PSV during respiratory failure
arm group label: PSV
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Inderpaul S Sehgal, MD,DM
role: Principal Investigator
affiliation: PGIMER,Chandigarh
facility: 
country: India
citation: Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Steingrub JS, Lagu T, Lindenauer PK. Epidemiology and outcomes of acute respiratory failure in the United States, 2001 to 2009: a national survey. J Hosp Med. 2013 Feb;8(2):76-82. doi: 10.1002/jhm.2004. Epub 2013 Jan 18.
PMID: 23335231
citation: Behrendt CE. Acute respiratory failure in the United States: incidence and 31-day survival. Chest. 2000 Oct;118(4):1100-5. doi: 10.1378/chest.118.4.1100.
PMID: 11035684
citation: Peter JV, Moran JL, Phillips-Hughes J, Warn D. Noninvasive ventilation in acute respiratory failure--a meta-analysis update. Crit Care Med. 2002 Mar;30(3):555-62. doi: 10.1097/00003246-200203000-00010.
PMID: 11990914
citation: Girou E, Schortgen F, Delclaux C, Brun-Buisson C, Blot F, Lefort Y, Lemaire F, Brochard L. Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients. JAMA. 2000 Nov 8;284(18):2361-7. doi: 10.1001/jama.284.18.2361.
PMID: 11066187
citation: Georgopoulos D, Prinianakis G, Kondili E. Bedside waveforms interpretation as a tool to identify patient-ventilator asynchronies. Intensive Care Med. 2006 Jan;32(1):34-47. doi: 10.1007/s00134-005-2828-5. Epub 2005 Nov 9.
PMID: 16283171
citation: Vignaux L, Vargas F, Roeseler J, Tassaux D, Thille AW, Kossowsky MP, Brochard L, Jolliet P. Patient-ventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study. Intensive Care Med. 2009 May;35(5):840-6. doi: 10.1007/s00134-009-1416-5. Epub 2009 Jan 29.
PMID: 19183949
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Inderpaul singh
investigator title: Assistant Professor, Department of Pulmonary Medicine
mesh term: Respiratory Insufficiency
sharing ipd: Undecided
ipd description: Complete protocol and individual patient data after publication of results