<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/NCT03006354</url>
  </required_header>
  <id_info>
    <org_study_id>2011-KAEK-25 2016/22-06</org_study_id>
    <nct_id>NCT03006354</nct_id>
  </id_info>
  <brief_title>nHFOV Versus nCPAP in Transient Tachypnea of the Newborn</brief_title>
  <official_title>Nasal High Frequency Oscillatory Ventilation Versus Nasal Continuous Positive Airway Pressure in Late-Preterm and Term Infants With Transient Tachypnea of the Newborn: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bursa Yüksek İhtisas Education and Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bursa Yüksek İhtisas Education and Research Hospital</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>
      In this prospective, randomised clinical trial the investigators aim to assess if nasal high&#xD;
      frequency oscillatory ventilation (nHFOV) could be used as the primary modality of&#xD;
      respiratory support in late preterm and term infants with transient tachypnea of the newborn&#xD;
      requiring non-invasive ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND: Non-invasive High Frequency Oscillatory Ventilation (nHFOV), aims to combine the&#xD;
      efficacy of high frequency ventilation with the gentleness of non-invasive support and&#xD;
      current evidence suggests that nHFOV may be superior to other non-invasive modes in terms of&#xD;
      supporting alveolar ventilation. There are now several published neonatal studies of nHFOV&#xD;
      therapy as a rescue mode even in the premature infants; however to date no studies have been&#xD;
      published on the efficacy of nHFOV as a primary mode of non-invasive support. The&#xD;
      investigators aim to assess the efficacy of nHFOV in late-preterm and term infants with&#xD;
      transient tachypnea of the newborn as the primary mode of non-invasive support.&#xD;
&#xD;
      METHOD: The investigators propose to test the effectiveness of nHFOV in late-preterm and term&#xD;
      neonates with transient tachypnea of the newborn (TTN) with a Silverman Score of 4 or above&#xD;
      on admission who require non-invasive respiratory support. Nasal high frequency oscillatory&#xD;
      ventilation may be effective in decreasing duration of non-invasive respiratory support and&#xD;
      total oxygen therapy (H1 hypotheses).&#xD;
&#xD;
      The current literature estimates the incidence of transient tachypnea of the newborn to be&#xD;
      5.7 per 1000 births. Assuming that a 5% difference of the primary outcome between the groups&#xD;
      is significant, when the alpha value is set at 0.05 and power of the study at 80%, 220&#xD;
      infants must be recruited for each arm (nCPAP and nHFOV) under investigation.&#xD;
&#xD;
      Chest X-ray, complete blood count, C-reactive protein and capillary blood gas analysis (as&#xD;
      per unit protocol) will be obtained upon admission to the neonatal intensive care unit. A&#xD;
      Silverman Score will be obtained for each participant upon admission and those with a score&#xD;
      of 4 and above will be supported with one of the methods (with randomization).&#xD;
&#xD;
      Initial nHFOV settings are: MAP: 8cmH2O, Frequency:10 MHz, Amplitude:35 cmH2O (will be&#xD;
      adjusted to achieve adequate chest wall vibration), I:E=1:1 and FiO2: adjusted to keep&#xD;
      preductal sPO2 between %90-95. Initial nCPAP settings are: PEEP:6 cmH2O and FiO2: adjusted to&#xD;
      keep preductal sPO2 between %90-95. Failure of the primary mode is defined as FiO2&#xD;
      requirement of &gt;%60, capillary blood gas obtained at the 4th hour of therapy showing pH&lt;7.20&#xD;
      or pCO2&gt;65 cmH2O. When nCPAP or nHFOV failure occurs, nasal intermittent positive pressure&#xD;
      ventilation (nIPPV) will be applied as a rescue therapy with the following settings:&#xD;
      Frequency:30/min, PIP:18 cmH2O, PEEP:6 cmH2O, inspiration time:0.50 sec., inspiratory flow:10&#xD;
      L/min, FiO2:adjusted to keep preductal sPO2 between %90-95. If the rescue mode fails, the&#xD;
      infant will be intubated and conventional mechanical ventilation will be initiated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Anticipated">June 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2018</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>Time to cessation of non-invasive positive pressure respiratory support</measure>
    <time_frame>72 hours</time_frame>
    <description>Cessation of nasal flaring, grunting and chest wall retractions (Silverman Score of 0) are indicators of readiness for discontinuation non-invasive positive pressure respiratory support.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to cessation of supplemental oxygen</measure>
    <time_frame>120 hours</time_frame>
    <description>Total duration of oxygen support of &gt;21%</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to discharge from hospital</measure>
    <time_frame>120 hours</time_frame>
    <description>Discharge time</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pneumothorax</measure>
    <time_frame>72 hours</time_frame>
    <description>Number of pneumothoraces requiring tube thoracostomy in each group</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">440</enrollment>
  <condition>Transient Tachypnea of the Newborn</condition>
  <arm_group>
    <arm_group_label>nHFOV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ventilator-derived nHFOV will be administered using binasal prongs. Standard Device: Leoni-Plus or Leoni-2 Ventilator, Heinen Löwenstein, Germany Initial nHFOV settings are: MAP: 8cmH2O, Frequency:10 MHz, Amplitude:35 cmH2O (will be adjusted to achieve adequate chest wall vibration), I:E=1:1 and FiO2: adjusted to keep preductal sPO2 between %90-95.&#xD;
Failure is defined as FiO2 requirement of &gt;%60, capillary blood gas obtained at the 4th hour of therapy showing pH&lt;7.20 or pCO2&gt;65 cmH2O.&#xD;
When nHFOV failure occurs, nasal intermittent positive pressure ventilation (nIPPV) will be applied as a rescue therapy with the following settings: Frequency:30/min, PIP:18 cmH2O, PEEP:6 cmH2O, inspiration time:0.50 sec., inspiratory flow:10 L/min, FiO2:adjusted to keep preductal sPO2 between %90-95.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nCPAP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ventilator-derived nCPAP will be administered using binasal prongs. Standard Device: Leoni-Plus or Leoni-2 Ventilator, Heinen Löwenstein, Germany Initial nCPAP settings are: PEEP:6 cmH2O and FiO2: adjusted to keep preductal sPO2 between %90-95.&#xD;
Failure is defined as FiO2 requirement of &gt;%60, capillary blood gas obtained at the 4th hour of therapy showing pH&lt;7.20 or pCO2&gt;65 cmH2O.&#xD;
When nCPAP failure occurs, nasal intermittent positive pressure ventilation (nIPPV) will be applied as a rescue therapy with the following settings: Frequency:30/min, PIP:18 cmH2O, PEEP:6 cmH2O, inspiration time:0.50 sec., inspiratory flow:10 L/min, FiO2:adjusted to keep preductal sPO2 between %90-95.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>nHFOV</intervention_name>
    <description>Ventilator (Leoni-Plus Ventilator, Heinen-Lowenstein, Germany) derived high frequency oscillatory ventilation, using binasal prongs</description>
    <arm_group_label>nHFOV</arm_group_label>
    <other_name>nasal high frequency oscillatory ventilation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>nCPAP</intervention_name>
    <description>Ventilator (Leoni-Plus or Leoni-2 Ventilator, Heinen-Lowenstein, Germany) derived high frequency oscillatory ventilation, using binasal prongs</description>
    <arm_group_label>nCPAP</arm_group_label>
    <other_name>nasal continuous positive airway pressure</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Gestational age at birth between 34 and 42 weeks of gestation&#xD;
&#xD;
          -  Admission to Bursa Yüksek Ihtisas Teaching Hospital, NICU during the first 24 hours of&#xD;
             life&#xD;
&#xD;
          -  Diagnosis of transient tachypnea of the newborn (TTN) within the first 24 hours of&#xD;
             life&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Gestational age at birth less than 34 weeks or greater than 42 weeks at birth&#xD;
&#xD;
          -  Chest X-ray or lung ultrasound finding indicating another respiratory disorder&#xD;
&#xD;
          -  Additional infant diagnosis of major cardiac disease&#xD;
&#xD;
          -  Additional infant diagnosis of major pulmonary disease other than TTN&#xD;
&#xD;
          -  Additional infant diagnosis of major congenital anomaly with potential to affect&#xD;
             respiratory status in the neonatal period&#xD;
&#xD;
          -  Additional infant diagnosis of infectious disease process potentially affecting&#xD;
             respiratory status in the neonatal period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>24 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mehmet N Cizmeci, M.D</last_name>
    <role>Study Director</role>
    <affiliation>Bursa Yuksek Ihtisas Teaching Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emre Baldan, M.D</last_name>
    <phone>+905456467876</phone>
    <email>emrebaldan@e-mail.com.tr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ipek Guney Varal, M.D</last_name>
    <phone>+905323413389</phone>
    <email>ibettyg@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Health Sciences, Bursa Yuksek Ihtisas Teaching Hospital</name>
      <address>
        <city>Bursa</city>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mehmet N Cizmeci, M.D</last_name>
      <phone>+905056576539</phone>
      <email>nevzatcizmeci@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Ipek G Varal, M.D</last_name>
      <phone>+905323413389</phone>
      <email>ibettyg@yahoo.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <results_reference>
    <citation>Fischer HS, Bohlin K, Buhrer C, Schmalisch G, Cremer M, Reiss I, Czernik C. Nasal high-frequency oscillation ventilation in neonates: a survey in five European countries. Eur J Pediatr. 2015 Apr;174(4):465-71. doi: 10.1007/s00431-014-2419-y. Epub 2014 Sep 18.</citation>
    <PMID>25227281</PMID>
  </results_reference>
  <results_reference>
    <citation>De Luca D, Dell'Orto V. Non-invasive high-frequency oscillatory ventilation in neonates: review of physiology, biology and clinical data. Arch Dis Child Fetal Neonatal Ed. 2016 Nov;101(6):F565-F570. doi: 10.1136/archdischild-2016-310664. Epub 2016 Jun 28.</citation>
    <PMID>27354382</PMID>
  </results_reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>March 6, 2017</last_update_submitted>
  <last_update_submitted_qc>March 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bursa Yüksek İhtisas Education and Research Hospital</investigator_affiliation>
    <investigator_full_name>Mehmet Nevzat Çizmeci</investigator_full_name>
    <investigator_title>Associate Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>high frequency oscillatory ventilation</keyword>
  <keyword>newborn</keyword>
  <keyword>noninvasive ventilation</keyword>
  <keyword>transient tachypnea of the newborn</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tachypnea</mesh_term>
    <mesh_term>Transient Tachypnea of the Newborn</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/NCT03006354
org study id: 2011-KAEK-25 2016/22-06
nct id: NCT03006354
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this prospective, randomised clinical trial the investigators aim to assess if nasal high
      frequency oscillatory ventilation (nHFOV) could be used as the primary modality of
      respiratory support in late preterm and term infants with transient tachypnea of the newborn
      requiring non-invasive ventilation.
BACKGROUND: Non-invasive High Frequency Oscillatory Ventilation (nHFOV), aims to combine the
      efficacy of high frequency ventilation with the gentleness of non-invasive support and
      current evidence suggests that nHFOV may be superior to other non-invasive modes in terms of
      supporting alveolar ventilation. There are now several published neonatal studies of nHFOV
      therapy as a rescue mode even in the premature infants; however to date no studies have been
      published on the efficacy of nHFOV as a primary mode of non-invasive support. The
      investigators aim to assess the efficacy of nHFOV in late-preterm and term infants with
      transient tachypnea of the newborn as the primary mode of non-invasive support.

      METHOD: The investigators propose to test the effectiveness of nHFOV in late-preterm and term
      neonates with transient tachypnea of the newborn (TTN) with a Silverman Score of 4 or above
      on admission who require non-invasive respiratory support. Nasal high frequency oscillatory
      ventilation may be effective in decreasing duration of non-invasive respiratory support and
      total oxygen therapy (H1 hypotheses).

      The current literature estimates the incidence of transient tachypnea of the newborn to be
      5.7 per 1000 births. Assuming that a 5% difference of the primary outcome between the groups
      is significant, when the alpha value is set at 0.05 and power of the study at 80%, 220
      infants must be recruited for each arm (nCPAP and nHFOV) under investigation.

      Chest X-ray, complete blood count, C-reactive protein and capillary blood gas analysis (as
      per unit protocol) will be obtained upon admission to the neonatal intensive care unit. A
      Silverman Score will be obtained for each participant upon admission and those with a score
      of 4 and above will be supported with one of the methods (with randomization).

      Initial nHFOV settings are: MAP: 8cmH2O, Frequency:10 MHz, Amplitude:35 cmH2O (will be
      adjusted to achieve adequate chest wall vibration), I:E=1:1 and FiO2: adjusted to keep
      preductal sPO2 between %90-95. Initial nCPAP settings are: PEEP:6 cmH2O and FiO2: adjusted to
      keep preductal sPO2 between %90-95. Failure of the primary mode is defined as FiO2
      requirement of >%60, capillary blood gas obtained at the 4th hour of therapy showing pH<7.20
      or pCO2>65 cmH2O. When nCPAP or nHFOV failure occurs, nasal intermittent positive pressure
      ventilation (nIPPV) will be applied as a rescue therapy with the following settings:
      Frequency:30/min, PIP:18 cmH2O, PEEP:6 cmH2O, inspiration time:0.50 sec., inspiratory flow:10
      L/min, FiO2:adjusted to keep preductal sPO2 between %90-95. If the rescue mode fails, the
      infant will be intubated and conventional mechanical ventilation will be initiated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to cessation of non-invasive positive pressure respiratory support
time frame: 72 hours
description: Cessation of nasal flaring, grunting and chest wall retractions (Silverman Score of 0) are indicators of readiness for discontinuation non-invasive positive pressure respiratory support.
measure: Time to cessation of supplemental oxygen
time frame: 120 hours
description: Total duration of oxygen support of >21%
measure: Time to discharge from hospital
time frame: 120 hours
description: Discharge time
measure: Pneumothorax
time frame: 72 hours
description: Number of pneumothoraces requiring tube thoracostomy in each group
arm group label: nHFOV
arm group type: Experimental
description: Ventilator-derived nHFOV will be administered using binasal prongs. Standard Device: Leoni-Plus or Leoni-2 Ventilator, Heinen Löwenstein, Germany Initial nHFOV settings are: MAP: 8cmH2O, Frequency:10 MHz, Amplitude:35 cmH2O (will be adjusted to achieve adequate chest wall vibration), I:E=1:1 and FiO2: adjusted to keep preductal sPO2 between %90-95.
Failure is defined as FiO2 requirement of >%60, capillary blood gas obtained at the 4th hour of therapy showing pH<7.20 or pCO2>65 cmH2O.
When nHFOV failure occurs, nasal intermittent positive pressure ventilation (nIPPV) will be applied as a rescue therapy with the following settings: Frequency:30/min, PIP:18 cmH2O, PEEP:6 cmH2O, inspiration time:0.50 sec., inspiratory flow:10 L/min, FiO2:adjusted to keep preductal sPO2 between %90-95.
arm group label: nCPAP
arm group type: Active Comparator
description: Ventilator-derived nCPAP will be administered using binasal prongs. Standard Device: Leoni-Plus or Leoni-2 Ventilator, Heinen Löwenstein, Germany Initial nCPAP settings are: PEEP:6 cmH2O and FiO2: adjusted to keep preductal sPO2 between %90-95.
Failure is defined as FiO2 requirement of >%60, capillary blood gas obtained at the 4th hour of therapy showing pH<7.20 or pCO2>65 cmH2O.
When nCPAP failure occurs, nasal intermittent positive pressure ventilation (nIPPV) will be applied as a rescue therapy with the following settings: Frequency:30/min, PIP:18 cmH2O, PEEP:6 cmH2O, inspiration time:0.50 sec., inspiratory flow:10 L/min, FiO2:adjusted to keep preductal sPO2 between %90-95.
intervention type: Device
intervention name: nHFOV
description: Ventilator (Leoni-Plus Ventilator, Heinen-Lowenstein, Germany) derived high frequency oscillatory ventilation, using binasal prongs
arm group label: nHFOV
other name: nasal high frequency oscillatory ventilation
intervention type: Device
intervention name: nCPAP
description: Ventilator (Leoni-Plus or Leoni-2 Ventilator, Heinen-Lowenstein, Germany) derived high frequency oscillatory ventilation, using binasal prongs
arm group label: nCPAP
other name: nasal continuous positive airway pressure
criteria: 
gender: All
minimum age: N/A
maximum age: 24 Hours
healthy volunteers: No
last name: Mehmet N Cizmeci, M.D
role: Study Director
affiliation: Bursa Yuksek Ihtisas Teaching Hospital
last name: Emre Baldan, M.D
phone: +905456467876
email: emrebaldan@e-mail.com.tr
last name: Ipek Guney Varal, M.D
phone: +905323413389
email: ibettyg@yahoo.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Turkey
citation: Fischer HS, Bohlin K, Buhrer C, Schmalisch G, Cremer M, Reiss I, Czernik C. Nasal high-frequency oscillation ventilation in neonates: a survey in five European countries. Eur J Pediatr. 2015 Apr;174(4):465-71. doi: 10.1007/s00431-014-2419-y. Epub 2014 Sep 18.
PMID: 25227281
citation: De Luca D, Dell'Orto V. Non-invasive high-frequency oscillatory ventilation in neonates: review of physiology, biology and clinical data. Arch Dis Child Fetal Neonatal Ed. 2016 Nov;101(6):F565-F570. doi: 10.1136/archdischild-2016-310664. Epub 2016 Jun 28.
PMID: 27354382
responsible party type: Principal Investigator
investigator affiliation: Bursa Yüksek İhtisas Education and Research Hospital
investigator full name: Mehmet Nevzat Çizmeci
investigator title: Associate Professor of Pediatrics
mesh term: Tachypnea
mesh term: Transient Tachypnea of the Newborn
sharing ipd: No