<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/NCT02236559</url>
  </required_header>
  <id_info>
    <org_study_id>RP-EDPF2014001Dev</org_study_id>
    <nct_id>NCT02236559</nct_id>
  </id_info>
  <brief_title>High Flow Therapy for the Treatment of Respiratory Failure in the ED</brief_title>
  <official_title>Vapotherm High Flow Therapy for the Treatment of Respiratory Failure in the ED: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vapotherm, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Texas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Memorial Hermann Texas Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Piedmont Athens Regional Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Tennessee</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Erlanger Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Memorial Hermann The Woodlands</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McLeod Regional Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vapotherm, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective of this study is to determine if Vapotherm high flow nasal cannula&#xD;
      therapy (HFT), when used to treat respiratory failure in the ED, is at least equivalent to&#xD;
      the current standard of care for non-invasive ventilatory support, non-invasive positive&#xD;
      pressure mask ventilation (NIPPV). Moreover, this study will investigate the potential that&#xD;
      HFT has possible advantages over NIPPV, such as decreased time to patient stability from&#xD;
      respiratory failure, and the ease of use as a first line intervention for respiratory failure&#xD;
      in the ED environment.&#xD;
&#xD;
      The hypothesis is that HFT via the Vapotherm Precision Flow will demonstrate clinical&#xD;
      non-inferiority when compared to NIPPV with regard to treatment failure by way of an impact&#xD;
      on ventilation indices and a lower intolerance rate, and have a positive association with&#xD;
      hospital disposition and length of stay.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">February 2017</completion_date>
  <primary_completion_date type="Actual">September 2016</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment Failure Rate</measure>
    <time_frame>Within 72 hrs</time_frame>
    <description>Determine the efficacy of HFT compared to NIPPV in treating respiratory failure. The primary endpoint will be treatment failure within 72 hrs as determined by intubation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 1</measure>
    <time_frame>At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</time_frame>
    <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventialtion (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 2</measure>
    <time_frame>At baseline, 30 minutes, 60 minutes, 90 minutes, 4 hours, and treatment failure if applicable</time_frame>
    <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Respiratory rate recorded at one and four hours, and at treatment failure if applicable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 3</measure>
    <time_frame>At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</time_frame>
    <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. SpO2 (a measurement of blood oxygen) recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 4</measure>
    <time_frame>At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</time_frame>
    <description>Evaluate the capability of HFT, compared to NIPPV, to affect indices of ventilation. Patient discomfort as rated on a VAS recorded at one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).. NOTE: Due to need for patients to be alert and provide this rating, the number analyzed is less than the total patients in the trial.&#xD;
VAS: Visual Analogue Scale. A Likert scale of facial expressions ranging from a smiley face to a frowning face used to assess the subjects' subjective level of dyspnea. Minimum 0 (no discomfort) to Maximum 5 (maximum discomfort).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 5</measure>
    <time_frame>at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable)</time_frame>
    <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Modified Borg score recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable). NOTE: Due to the need for patients to be alert and able to provide this score, the number analyzed is less than the total patients in the trial.&#xD;
A modified Borg scale was used to ask the patient to describe their effort on a scale of 0 to 10, where 10 is extreme discomfort.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 6</measure>
    <time_frame>At one and four hours</time_frame>
    <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (pH), a measurement of CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 7</measure>
    <time_frame>At one and four hours</time_frame>
    <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (PCO2), a measure of CO2, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 8</measure>
    <time_frame>At one and four hours</time_frame>
    <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (HCO3), a meausre of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilatory Indices 9</measure>
    <time_frame>At one and four hours</time_frame>
    <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (base excess), a measure of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay</measure>
    <time_frame>Duration of hospital visit</time_frame>
    <description>Evaluate the capability of HVNI, compared to NIPPV, to affect average length of stay.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">204</enrollment>
  <condition>Acute Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>Noninvasive positive pressure ventilation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV. Initial pressures will be at low end of suggested range but can be increased as rapidly as necessary to alleviate respiratory distress. Targets should be to lower respiratory rate to the low 20s and achieve tidal volumes of 6-8 ml/kg ideal body weight. If patients find pressures uncomfortably high, they can be lowered as necessary by 1 to 2 cmH2O decrements to enhance tolerance. EPAP (PEEP) can also be adjusted upward as needed to reduce triggering effort (by counterbalancing auto-PEEP) or to improve oxygenation.&#xD;
FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 with an EPAP (PEEP) of not more than 10 cm H2O to maintain a PaO2 &gt; 88%.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High flow therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. Initial flow will be set to 35 L/min but can be decreased or increased as rapidly as necessary to alleviate respiratory distress and optimize patient comfort. Targets should be to lower respiratory rate to the low 20s and with a HFT flow rate between 20 to 35 L/min. Starting temperature will be between 35 to 37 C; if patients find the gas temperature to be uncomfortable, it can be lowered as necessary down to 33 C to enhance tolerance.&#xD;
FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 to maintain a PaO2 &gt; 88%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Noninvasive positive pressure ventilation (NIPPV)</intervention_name>
    <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV. Initial pressures will be at low end of suggested range but can be increased as rapidly as necessary to alleviate respiratory distress. Targets should be to lower respiratory rate to the low 20s and achieve tidal volumes of 6-8 ml/kg ideal body weight. If patients find pressures uncomfortably high, they can be lowered as necessary by 1 to 2 cmH2O decrements to enhance tolerance. EPAP (PEEP) can also be adjusted upward as needed to reduce triggering effort (by counterbalancing auto-PEEP) or to improve oxygenation.&#xD;
FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 with an EPAP (PEEP) of not more than 10 cm H2O to maintain a PaO2 &gt; 88%.</description>
    <arm_group_label>Noninvasive positive pressure ventilation</arm_group_label>
    <other_name>BIPAP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Vapotherm</intervention_name>
    <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. Initial flow will be set to 35 L/min but can be decreased or increased as rapidly as necessary to alleviate respiratory distress and optimize patient comfort. Targets should be to lower respiratory rate to the low 20s and with a HFT flow rate between 20 to 35 L/min. Starting temperature will be between 35 to 37 C; if patients find the gas temperature to be uncomfortable, it can be lowered as necessary down to 33 C to enhance tolerance. FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 to maintain a PaO2 &gt; 88%.</description>
    <arm_group_label>High flow therapy</arm_group_label>
    <other_name>High flow nasal cannula</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (&gt; 18 yrs of age)&#xD;
&#xD;
          -  Presentation with acute respiratory failure according to the following criteria:&#xD;
&#xD;
          -  If any of these are present: Respiratory Rate &gt;22 or labored; Suspected Acute&#xD;
             Respiratory Acidosis, as defined as pH &lt;7.32 on initial blood gas(either arterial or&#xD;
             venous); Hypoxemia, as defined as Pulse Ox &lt;92%;&#xD;
&#xD;
          -  Clinical decision to escalate therapy to non-invasive ventilatory support, or to&#xD;
             maintain non-invasive ventilatory support if delivered to the ED on such.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Suspected drug overdose&#xD;
&#xD;
          -  Cardiovascular instability as demonstrated by hypotension relative to initial clinical&#xD;
             presentation that requires immediate intervention&#xD;
&#xD;
          -  End stage cancer&#xD;
&#xD;
          -  Life expectancy &lt; 6 months&#xD;
&#xD;
          -  Respiratory arrest or significant respiratory depression on presentation&#xD;
&#xD;
          -  Glasgow Coma Scale score &lt; 9&#xD;
&#xD;
          -  Cardiac arrest on initial presentation&#xD;
&#xD;
          -  Need for emergent intubation&#xD;
&#xD;
          -  Known or suspected cerebrovascular accident&#xD;
&#xD;
          -  Known or suspected ST segment elevation myocardial infarction&#xD;
&#xD;
          -  Patients with increased risk of pulmonary aspiration&#xD;
&#xD;
          -  Agitation or uncooperativeness&#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>Pratik B Doshi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thomas L Miller, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Vapotherm, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Athens Regional Medical Center</name>
      <address>
        <city>Athens</city>
        <state>Georgia</state>
        <zip>30606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLeod Regional Medical Center</name>
      <address>
        <city>Florence</city>
        <state>South Carolina</state>
        <zip>29506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erlanger Health System</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hermann Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hermann The Woodlands</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <results_first_submitted>March 27, 2019</results_first_submitted>
  <results_first_submitted_qc>April 25, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 23, 2019</results_first_posted>
  <last_update_submitted>April 25, 2019</last_update_submitted>
  <last_update_submitted_qc>April 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>high flow therapy</keyword>
  <keyword>high flow nasal cannula</keyword>
  <keyword>acute respiratory failure</keyword>
  <keyword>noninvasive ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>24 patients randomized but not enrolled were excluded for meeting exclusion criteria (10), consent not obtained or withdrawn (6), bedside clinician not comfortable with enrollment after randomization (2), &amp; patient identified to not need NiPPV after initial evaluation, thus failing to meet inclusion criteria (6). One patient met multiple criteria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Noninvasive Positive Pressure Ventilation</title>
          <description>Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
        </group>
        <group group_id="P2">
          <title>High Velocity Nasal Insufflation</title>
          <description>High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort.The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="112"/>
                <participants group_id="P2" count="116"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="100"/>
                <participants group_id="P2" count="104"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Met Exclusion</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Did not Meet Inclusion</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject Did Not Consent</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Noninvasive Positive Pressure Ventilation (NiPPV)</title>
          <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of Noninvasive positive-pressure ventilation (NiPPV). NiPPV(Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
        </group>
        <group group_id="B2">
          <title>High Velocity Nasal Insufflation (HVNI)</title>
          <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of High Velocity Nasal Insufflation (HVNI). HVNI (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="100"/>
            <count group_id="B2" value="104"/>
            <count group_id="B3" value="204"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.3" spread="14.8"/>
                    <measurement group_id="B2" value="63.4" spread="13.6"/>
                    <measurement group_id="B3" value="63.3" spread="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="60"/>
                    <measurement group_id="B3" value="114"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>American Indian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>African</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="100"/>
                    <measurement group_id="B2" value="104"/>
                    <measurement group_id="B3" value="204"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Presenting Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Asthma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Congestive Heart Failure</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Chronic heart failure</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Chronic Obstructive Pulmonary Disorder (COPD)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="79"/>
                  </measurement_list>
                </category>
                <category>
                  <title>General dyspnea</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Discharge Diagnosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Asthma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute decompensated heart failure</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute COPD exacerbation</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute hypercapnic respiratory failure</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute hypoxic respiratory failure</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute hypercapnic and hypoxic respiratory failure</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Pneumonia/sepsis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Treatment Failure Rate</title>
        <description>Determine the efficacy of HFT compared to NIPPV in treating respiratory failure. The primary endpoint will be treatment failure within 72 hrs as determined by intubation.</description>
        <time_frame>Within 72 hrs</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Failure Rate</title>
          <description>Determine the efficacy of HFT compared to NIPPV in treating respiratory failure. The primary endpoint will be treatment failure within 72 hrs as determined by intubation.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Intubated at 72 Hours</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Intubated at 72 hours</title>
                  <measurement_list>
                    <measurement group_id="O1" value="87"/>
                    <measurement group_id="O2" value="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 1</title>
        <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventialtion (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia.</description>
        <time_frame>At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 1</title>
          <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventialtion (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>beats per min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Heart Rate at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101" spread="21.3"/>
                    <measurement group_id="O2" value="100.4" spread="21.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate at 30 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.4" spread="22"/>
                    <measurement group_id="O2" value="95.6" spread="20.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="88"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.7" spread="20.4"/>
                    <measurement group_id="O2" value="94" spread="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate at 90 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="84"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.2" spread="21.6"/>
                    <measurement group_id="O2" value="91.8" spread="17.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="76"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.6" spread="18.2"/>
                    <measurement group_id="O2" value="9.21" spread="17.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.9" spread="33.5"/>
                    <measurement group_id="O2" value="106.4" spread="29.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 2</title>
        <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Respiratory rate recorded at one and four hours, and at treatment failure if applicable.</description>
        <time_frame>At baseline, 30 minutes, 60 minutes, 90 minutes, 4 hours, and treatment failure if applicable</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 2</title>
          <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Respiratory rate recorded at one and four hours, and at treatment failure if applicable.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>breaths per min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Respiratory Rate at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.3" spread="8.2"/>
                    <measurement group_id="O2" value="31.3" spread="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate at 30 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.6" spread="7.6"/>
                    <measurement group_id="O2" value="26.0" spread="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="88"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.4" spread="6.6"/>
                    <measurement group_id="O2" value="23.9" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate at 90 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="84"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.7" spread="6.4"/>
                    <measurement group_id="O2" value="22.9" spread="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="76"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.1" spread="4.8"/>
                    <measurement group_id="O2" value="22.2" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory Rate at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.4" spread="10.2"/>
                    <measurement group_id="O2" value="26.4" spread="11.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 3</title>
        <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. SpO2 (a measurement of blood oxygen) recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</description>
        <time_frame>At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 3</title>
          <description>Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. SpO2 (a measurement of blood oxygen) recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>% SpO2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SpO2 at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.5" spread="8.9"/>
                    <measurement group_id="O2" value="93.2" spread="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SpO2 at 30 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.8" spread="3.3"/>
                    <measurement group_id="O2" value="97.5" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SpO2 at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="88"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.8" spread="3"/>
                    <measurement group_id="O2" value="97.6" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SpO2 at 90 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="84"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.7" spread="2.3"/>
                    <measurement group_id="O2" value="97.8" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SpO2 at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                    <count group_id="O2" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.8" spread="2.8"/>
                    <measurement group_id="O2" value="97.2" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SpO2 at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.4" spread="6.1"/>
                    <measurement group_id="O2" value="93.3" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 4</title>
        <description>Evaluate the capability of HFT, compared to NIPPV, to affect indices of ventilation. Patient discomfort as rated on a VAS recorded at one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).. NOTE: Due to need for patients to be alert and provide this rating, the number analyzed is less than the total patients in the trial.&#xD;
VAS: Visual Analogue Scale. A Likert scale of facial expressions ranging from a smiley face to a frowning face used to assess the subjects' subjective level of dyspnea. Minimum 0 (no discomfort) to Maximum 5 (maximum discomfort).</description>
        <time_frame>At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol. Some participants were unable to give scores due to health status.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 4</title>
          <description>Evaluate the capability of HFT, compared to NIPPV, to affect indices of ventilation. Patient discomfort as rated on a VAS recorded at one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).. NOTE: Due to need for patients to be alert and provide this rating, the number analyzed is less than the total patients in the trial.&#xD;
VAS: Visual Analogue Scale. A Likert scale of facial expressions ranging from a smiley face to a frowning face used to assess the subjects' subjective level of dyspnea. Minimum 0 (no discomfort) to Maximum 5 (maximum discomfort).</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol. Some participants were unable to give scores due to health status.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>VAS at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" spread=".5"/>
                    <measurement group_id="O2" value="4" spread=".5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS at 30 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="85"/>
                    <count group_id="O2" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" spread="0.5"/>
                    <measurement group_id="O2" value="3" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="91"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread=".5"/>
                    <measurement group_id="O2" value="2" spread=".5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS at 90 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="75"/>
                    <count group_id="O2" value="84"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread="0.5"/>
                    <measurement group_id="O2" value="2" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="69"/>
                    <count group_id="O2" value="72"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread=".5"/>
                    <measurement group_id="O2" value="2" spread=".4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>VAS at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" spread="3.5"/>
                    <measurement group_id="O2" value="3" spread="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 5</title>
        <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Modified Borg score recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable). NOTE: Due to the need for patients to be alert and able to provide this score, the number analyzed is less than the total patients in the trial.&#xD;
A modified Borg scale was used to ask the patient to describe their effort on a scale of 0 to 10, where 10 is extreme discomfort.</description>
        <time_frame>at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable)</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol. Some participants were unable to give scores due to health status.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 5</title>
          <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Modified Borg score recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable). NOTE: Due to the need for patients to be alert and able to provide this score, the number analyzed is less than the total patients in the trial.&#xD;
A modified Borg scale was used to ask the patient to describe their effort on a scale of 0 to 10, where 10 is extreme discomfort.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol. Some participants were unable to give scores due to health status.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Borg Score at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.5" spread="2.6"/>
                    <measurement group_id="O2" value="6.3" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Borg Score at 30 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" spread="2.7"/>
                    <measurement group_id="O2" value="4.3" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Borg Score at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="90"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="2.2"/>
                    <measurement group_id="O2" value="3.5" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Borg Score at 90 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="78"/>
                    <count group_id="O2" value="83"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" spread="2.2"/>
                    <measurement group_id="O2" value="3.3" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Borg Score at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="71"/>
                    <count group_id="O2" value="71"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="1.8"/>
                    <measurement group_id="O2" value="2.6" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Borg Score at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1" spread="3"/>
                    <measurement group_id="O2" value="4.9" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 6</title>
        <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (pH), a measurement of CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
        <time_frame>At one and four hours</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 6</title>
          <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (pH), a measurement of CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>pH</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>pH at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.33" spread=".08"/>
                    <measurement group_id="O2" value="7.35" spread=".1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>pH at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.34" spread=".07"/>
                    <measurement group_id="O2" value="7.36" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>pH at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="72"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.36" spread=".06"/>
                    <measurement group_id="O2" value="7.38" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>pH at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.19" spread="0.04"/>
                    <measurement group_id="O2" value="7.25" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 7</title>
        <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (PCO2), a measure of CO2, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
        <time_frame>At one and four hours</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 7</title>
          <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (PCO2), a measure of CO2, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PCO2 at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.7" spread="25"/>
                    <measurement group_id="O2" value="53.4" spread="20.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PCO2 at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.2" spread="21.5"/>
                    <measurement group_id="O2" value="52.0" spread="19.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PCO2 at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="72"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.5" spread="17.8"/>
                    <measurement group_id="O2" value="46.3" spread="12.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PCO2 at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.2" spread="33.3"/>
                    <measurement group_id="O2" value="69.2" spread="32.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 8</title>
        <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (HCO3), a meausre of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
        <time_frame>At one and four hours</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 8</title>
          <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (HCO3), a meausre of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>mEq/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HCO3 at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.8" spread="9.5"/>
                    <measurement group_id="O2" value="28.6" spread="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HCO3 at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.4" spread="9.5"/>
                    <measurement group_id="O2" value="28.4" spread="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HCO3 at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="72"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.3" spread="9.2"/>
                    <measurement group_id="O2" value="26.9" spread="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HCO3 at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.5" spread="15.4"/>
                    <measurement group_id="O2" value="30.1" spread="13.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilatory Indices 9</title>
        <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (base excess), a measure of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
        <time_frame>At one and four hours</time_frame>
        <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilatory Indices 9</title>
          <description>Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (base excess), a measure of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.&#xD;
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.</description>
          <population>If treatment failed prior to followup recording, subsequent data was not collected per the protocol.</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Base excess at Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.87" spread="7.76"/>
                    <measurement group_id="O2" value="2.35" spread="8.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Base excess at 60 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.71" spread="7.92"/>
                    <measurement group_id="O2" value="2.3" spread="7.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Base excess at 240 min</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="72"/>
                    <count group_id="O2" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.14" spread="7.79"/>
                    <measurement group_id="O2" value="1.47" spread="5.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Base excess at Treatment Failure</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.12" spread="13.75"/>
                    <measurement group_id="O2" value="2.29" spread="12.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay</title>
        <description>Evaluate the capability of HVNI, compared to NIPPV, to affect average length of stay.</description>
        <time_frame>Duration of hospital visit</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Noninvasive Positive Pressure Ventilation</title>
            <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
          <group group_id="O2">
            <title>High Velocity Nasal Insufflation</title>
            <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay</title>
          <description>Evaluate the capability of HVNI, compared to NIPPV, to affect average length of stay.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
                <count group_id="O2" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="4.4"/>
                    <measurement group_id="O2" value="6.8" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Noninvasive Positive Pressure Ventilation</title>
          <description>Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV.Noninvasive positive-pressure ventilation (Respironics Vision V60; Philips Healthcare, Murrysville, PA) was initiated with an oronasal mask, with inspiratory and expiratory positive airway pressures (IPAP, EPAP) set at the lower end of the following settings and increased as necessary to alleviate respiratory distress: IPAP 10 to 20 cm H2O (or 5 to 15 cm H2O above EPAP), and EPAP 5 to 10 cm H2O. FiO2 was initiated at 1.0 for noninvasive positive-pressure ventilation. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
        </group>
        <group group_id="E2">
          <title>High Velocity Nasal Insufflation</title>
          <description>Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. High-velocity nasal insufflation (Precision Flow; Vapotherm, Inc, Exeter, NH) (Figure 1) using a small-bore nasal cannula was initiated with a flow rate set to 35 L/min, with a starting temperature between 35C and 37C and FiO2 at 1.0. Adjustments in flow (up to 40 L/min) and temperature (typically between 35C and 37C) were made to alleviate respiratory distress and optimize comfort. The target for each intervention was to decrease breathing rate to fewer than 25 breaths/min and optimize comfort, whereas FiO2 was adjusted to maintain a pulse oximetry reading (SpO2) greater than 88%. The study model provided for having a respiratory therapist at bedside for the first 4 hours, which facilitated rapid changing of settings as needed.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="02" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Death Outside Study Window</sub_title>
                <description>Cardiac arrest leading to death prior to discharge but outside the study window. Determined by the principal investigator to not be study related.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="100"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="100"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="104"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Pratik Doshi, MD</name_or_title>
      <organization>McGovern Medical School at The University of Texas Health Science Center at Houston</organization>
      <email>pratik.b.doshi@uth.tmc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02236559
org study id: RP-EDPF2014001Dev
nct id: NCT02236559
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The overall objective of this study is to determine if Vapotherm high flow nasal cannula
      therapy (HFT), when used to treat respiratory failure in the ED, is at least equivalent to
      the current standard of care for non-invasive ventilatory support, non-invasive positive
      pressure mask ventilation (NIPPV). Moreover, this study will investigate the potential that
      HFT has possible advantages over NIPPV, such as decreased time to patient stability from
      respiratory failure, and the ease of use as a first line intervention for respiratory failure
      in the ED environment.

      The hypothesis is that HFT via the Vapotherm Precision Flow will demonstrate clinical
      non-inferiority when compared to NIPPV with regard to treatment failure by way of an impact
      on ventilation indices and a lower intolerance rate, and have a positive association with
      hospital disposition and length of stay.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Treatment Failure Rate
time frame: Within 72 hrs
description: Determine the efficacy of HFT compared to NIPPV in treating respiratory failure. The primary endpoint will be treatment failure within 72 hrs as determined by intubation.
measure: Ventilatory Indices 1
time frame: At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
description: Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventialtion (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia.
measure: Ventilatory Indices 2
time frame: At baseline, 30 minutes, 60 minutes, 90 minutes, 4 hours, and treatment failure if applicable
description: Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Respiratory rate recorded at one and four hours, and at treatment failure if applicable.
measure: Ventilatory Indices 3
time frame: At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
description: Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. SpO2 (a measurement of blood oxygen) recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
measure: Ventilatory Indices 4
time frame: At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
description: Evaluate the capability of HFT, compared to NIPPV, to affect indices of ventilation. Patient discomfort as rated on a VAS recorded at one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).. NOTE: Due to need for patients to be alert and provide this rating, the number analyzed is less than the total patients in the trial.
VAS: Visual Analogue Scale. A Likert scale of facial expressions ranging from a smiley face to a frowning face used to assess the subjects' subjective level of dyspnea. Minimum 0 (no discomfort) to Maximum 5 (maximum discomfort).
measure: Ventilatory Indices 5
time frame: at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable)
description: Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Modified Borg score recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable). NOTE: Due to the need for patients to be alert and able to provide this score, the number analyzed is less than the total patients in the trial.
A modified Borg scale was used to ask the patient to describe their effort on a scale of 0 to 10, where 10 is extreme discomfort.
measure: Ventilatory Indices 6
time frame: At one and four hours
description: Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (pH), a measurement of CO2 levels, recorded at one and four hours, and at treatment failure if applicable.
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.
measure: Ventilatory Indices 7
time frame: At one and four hours
description: Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (PCO2), a measure of CO2, recorded at one and four hours, and at treatment failure if applicable.
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.
measure: Ventilatory Indices 8
time frame: At one and four hours
description: Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (HCO3), a meausre of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.
measure: Ventilatory Indices 9
time frame: At one and four hours
description: Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (base excess), a measure of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable.
NOTE: Due to test error, the number analyzed is less than the total patients in the trial.
measure: Length of Stay
time frame: Duration of hospital visit
description: Evaluate the capability of HVNI, compared to NIPPV, to affect average length of stay.
arm group label: Noninvasive positive pressure ventilation
arm group type: Active Comparator
description: Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV. Initial pressures will be at low end of suggested range but can be increased as rapidly as necessary to alleviate respiratory distress. Targets should be to lower respiratory rate to the low 20s and achieve tidal volumes of 6-8 ml/kg ideal body weight. If patients find pressures uncomfortably high, they can be lowered as necessary by 1 to 2 cmH2O decrements to enhance tolerance. EPAP (PEEP) can also be adjusted upward as needed to reduce triggering effort (by counterbalancing auto-PEEP) or to improve oxygenation.
FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 with an EPAP (PEEP) of not more than 10 cm H2O to maintain a PaO2 > 88%.
arm group label: High flow therapy
arm group type: Experimental
description: Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. Initial flow will be set to 35 L/min but can be decreased or increased as rapidly as necessary to alleviate respiratory distress and optimize patient comfort. Targets should be to lower respiratory rate to the low 20s and with a HFT flow rate between 20 to 35 L/min. Starting temperature will be between 35 to 37 C; if patients find the gas temperature to be uncomfortable, it can be lowered as necessary down to 33 C to enhance tolerance.
FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 to maintain a PaO2 > 88%.
intervention type: Device
intervention name: Noninvasive positive pressure ventilation (NIPPV)
description: Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV. Initial pressures will be at low end of suggested range but can be increased as rapidly as necessary to alleviate respiratory distress. Targets should be to lower respiratory rate to the low 20s and achieve tidal volumes of 6-8 ml/kg ideal body weight. If patients find pressures uncomfortably high, they can be lowered as necessary by 1 to 2 cmH2O decrements to enhance tolerance. EPAP (PEEP) can also be adjusted upward as needed to reduce triggering effort (by counterbalancing auto-PEEP) or to improve oxygenation.
FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 with an EPAP (PEEP) of not more than 10 cm H2O to maintain a PaO2 > 88%.
arm group label: Noninvasive positive pressure ventilation
other name: BIPAP
intervention type: Device
intervention name: Vapotherm
description: Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. Initial flow will be set to 35 L/min but can be decreased or increased as rapidly as necessary to alleviate respiratory distress and optimize patient comfort. Targets should be to lower respiratory rate to the low 20s and with a HFT flow rate between 20 to 35 L/min. Starting temperature will be between 35 to 37 C; if patients find the gas temperature to be uncomfortable, it can be lowered as necessary down to 33 C to enhance tolerance. FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 to maintain a PaO2 > 88%.
arm group label: High flow therapy
other name: High flow nasal cannula
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pratik B Doshi, MD
role: Principal Investigator
affiliation: University of Texas
last name: Thomas L Miller, PhD
role: Study Director
affiliation: Vapotherm, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Insufficiency
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 