<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/NCT04502576</url>
  </required_header>
  <id_info>
    <org_study_id>4443</org_study_id>
    <nct_id>NCT04502576</nct_id>
  </id_info>
  <brief_title>Helmet Noninvasive Ventilation vs. High-flow Nasal Cannula in Moderate-to-severe Acute Hypoxemic Respiratory Failure</brief_title>
  <acronym>HENIVOTpilot</acronym>
  <official_title>Helmet Noninvasive Ventilation vs. High-flow Nasal Cannula in Moderate-to-severe Acute Hypoxemic Respiratory Failure: an Open Label, Pilot, Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Università degli studi di Chieti</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Societa Italiana Anestesia Analgesia Rianimazione e Terapia Intensiva</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Helmet noninvasive ventilation and high-flow nasal cannula are novel tools for the first-line&#xD;
      treatment of acute hypoxemic respiratory failure. Compared to face-mask noninvasive&#xD;
      ventilation in randomized trials, both have improved clinical outcome of patients with&#xD;
      moderate-to-severe hypoxemic respiratory failure.&#xD;
&#xD;
      As compared to high-flow nasal cannula, helmet noninvasive ventilation improves oxygenation,&#xD;
      reduces inspiratory effort, respiratory rate and dyspnea. Whether these physiological&#xD;
      benefits are translated into improved outcome remains to be established.&#xD;
&#xD;
      The investigators designed a randomized trial to establish whether first line treatment with&#xD;
      Helmet noninvasive ventilation is capable of increasing the number of 28-day&#xD;
      respiratory-support-free days, as compared to high-flow nasal cannula in patients with&#xD;
      moderate-to-severe acute hypoxemic respiratory failure.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 13, 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Actual">January 10, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Respiratory-support free days within 28 days from randomization</measure>
    <time_frame>28 days</time_frame>
    <description>The number of days in which patients did not receive any form of respiratory support (i.e. high-flow nasal cannula, noninvasive ventilation, invasive mechanical ventilation)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endotracheal intubation</measure>
    <time_frame>28 days</time_frame>
    <description>The proportion of patients requiring endotracheal intubation in the two groups. The need for endotracheal intubation will be established with predefined criteria, which will be evaluated a posteriori by an independent adjudication committee</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Invasive ventilation-free days within 28 days from randomization</measure>
    <time_frame>28 days</time_frame>
    <description>The number of days in which patients did not receive invasive mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Invasive ventilation-free days within 60 days from randomization</measure>
    <time_frame>60 days</time_frame>
    <description>The number of days in which patients did not receive invasive mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygenation</measure>
    <time_frame>28 days</time_frame>
    <description>The ratio of PaO2 to FiO2 will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carbon dioxide</measure>
    <time_frame>28 days</time_frame>
    <description>PaCO2 will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dyspnea</measure>
    <time_frame>28 days</time_frame>
    <description>Dyspnea will be evaluated through a visual analog scale (0-10, where 10 represents the most sever symptom) will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory rate</measure>
    <time_frame>28 days</time_frame>
    <description>Respiratory rate will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-intensive care unit mortality</measure>
    <time_frame>90 days</time_frame>
    <description>Clinical outcome (dead/alive) at intensive care unit discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>90 days</time_frame>
    <description>Clinical outcome (dead/alive) at hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>90-day mortality</measure>
    <time_frame>90 days</time_frame>
    <description>Clinical outcome (dead/alive) at 90 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life after recovery</measure>
    <time_frame>1 year</time_frame>
    <description>Quality of life in survivors, assessed by Short Form-36 questionnaire</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>Respiratory Failure With Hypoxia</condition>
  <arm_group>
    <arm_group_label>High-flow nasal cannula</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>High-flow nasal cannula will be delivered with the Optiflow system. Initial set flow will be ≥ 50 /min and flows will be decreased in case of intolerance and/or according to patients' requirements: flows≥30 L/min will be mandatory in all enrolled patients. Humidification chamber (MR860, Fisher and Paykel healthcare, New Zealand) will be set at 37 °C or 34 °C according to patient's comfort. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%.&#xD;
The treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge. Weaning from high-flow will be considered as standardized criteria are met.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Helmet noninvasive ventilation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive continuous helmet pressure support ventilation for at least 16 hours/day the first 2 calendar days. Continuous noninvasive ventilation without interruptions will be strongly encouraged in the first 24 hours of treatment. The ventilator will be set in pressure support mode. Use of continuous positive airway pressure by flow generators and Venturi systems instead of pressure support ventilation will be allowed in case of shortage of ventilators. Maintenance of positive end-expiratory pressure ≥ 8-10 during the treatment is mandatory.&#xD;
After weaning and during any interruption from noninvasive ventilation, patients will undergo low-flow or high-flow oxygen, according to the decision of the attending physician.&#xD;
The treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Noninvasive respiratory support</intervention_name>
    <description>In both arms, the treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge.&#xD;
Patients will have to undergo the allocated treatment within 1 hour from the moment of randomization and within 24 hours from admission in the intensive care unit</description>
    <arm_group_label>Helmet noninvasive ventilation</arm_group_label>
    <arm_group_label>High-flow nasal cannula</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Acute-onset respiratory distress or flue-related symptoms Moderate-to-severe hypoxemia&#xD;
        (PaO2/FiO2&lt;=200 mmHg) PaCO2&lt;45 mmHg pH&gt;7.30&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Need for urgent endo-tracheal intubation Exacerbation of asthma or chronic obstructive&#xD;
        pulmonary disease Documented pneumothorax Clinical diagnosis of Cardiogenic pulmonary&#xD;
        oedema Do-not-intubate order Altered neurological status that requires immediate intubation&#xD;
        and/or making the patient uncooperative Thoracic or abdominal surgery in the previous 7&#xD;
        days Recent head surgery or anatomy that prevent the application of helmet or Optiflow to&#xD;
        patient's face&#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>Domenico Luca Grieco, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione Policlinico A. Gemelli IRCCS</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Massimo Antonelli, MD</last_name>
    <role>Study Director</role>
    <affiliation>Fondazione Policlinico A. Gemelli IRCCS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Policlinico di Sant'Orsola, Alma Mater Studiorum-Università di Bologna</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SS. Annunziata Hospital, Gabriele d'Annunzio University of Chieti-Pescara</name>
      <address>
        <city>Chieti</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera-Universitaria Arcispedale Sant'Anna, University of Ferrara</name>
      <address>
        <city>Ferrara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Infermi Hospital</name>
      <address>
        <city>Rimini</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitaro A. Gemelli IRCCS</name>
      <address>
        <city>Rome</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>November 18, 2021</last_update_submitted>
  <last_update_submitted_qc>November 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Data will be made available upon a reasonable request</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04502576
org study id: 4443
nct id: NCT04502576
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Helmet noninvasive ventilation and high-flow nasal cannula are novel tools for the first-line
      treatment of acute hypoxemic respiratory failure. Compared to face-mask noninvasive
      ventilation in randomized trials, both have improved clinical outcome of patients with
      moderate-to-severe hypoxemic respiratory failure.

      As compared to high-flow nasal cannula, helmet noninvasive ventilation improves oxygenation,
      reduces inspiratory effort, respiratory rate and dyspnea. Whether these physiological
      benefits are translated into improved outcome remains to be established.

      The investigators designed a randomized trial to establish whether first line treatment with
      Helmet noninvasive ventilation is capable of increasing the number of 28-day
      respiratory-support-free days, as compared to high-flow nasal cannula in patients with
      moderate-to-severe acute hypoxemic respiratory failure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Respiratory-support free days within 28 days from randomization
time frame: 28 days
description: The number of days in which patients did not receive any form of respiratory support (i.e. high-flow nasal cannula, noninvasive ventilation, invasive mechanical ventilation)
measure: Endotracheal intubation
time frame: 28 days
description: The proportion of patients requiring endotracheal intubation in the two groups. The need for endotracheal intubation will be established with predefined criteria, which will be evaluated a posteriori by an independent adjudication committee
measure: Invasive ventilation-free days within 28 days from randomization
time frame: 28 days
description: The number of days in which patients did not receive invasive mechanical ventilation
measure: Invasive ventilation-free days within 60 days from randomization
time frame: 60 days
description: The number of days in which patients did not receive invasive mechanical ventilation
measure: Oxygenation
time frame: 28 days
description: The ratio of PaO2 to FiO2 will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge
measure: Carbon dioxide
time frame: 28 days
description: PaCO2 will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge
measure: Dyspnea
time frame: 28 days
description: Dyspnea will be evaluated through a visual analog scale (0-10, where 10 represents the most sever symptom) will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge
measure: Respiratory rate
time frame: 28 days
description: Respiratory rate will be measured 1, 6, 12, 24 hours after randomization and then once daily up to intensive care unit discharge
measure: In-intensive care unit mortality
time frame: 90 days
description: Clinical outcome (dead/alive) at intensive care unit discharge
measure: In-hospital mortality
time frame: 90 days
description: Clinical outcome (dead/alive) at hospital discharge
measure: 90-day mortality
time frame: 90 days
description: Clinical outcome (dead/alive) at 90 days after randomization
measure: Quality of life after recovery
time frame: 1 year
description: Quality of life in survivors, assessed by Short Form-36 questionnaire
arm group label: High-flow nasal cannula
arm group type: Active Comparator
description: High-flow nasal cannula will be delivered with the Optiflow system. Initial set flow will be ≥ 50 /min and flows will be decreased in case of intolerance and/or according to patients' requirements: flows≥30 L/min will be mandatory in all enrolled patients. Humidification chamber (MR860, Fisher and Paykel healthcare, New Zealand) will be set at 37 °C or 34 °C according to patient's comfort. FiO2 will be titrated to obtain an SpO2≥92% and ≤98%.
The treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge. Weaning from high-flow will be considered as standardized criteria are met.
arm group label: Helmet noninvasive ventilation
arm group type: Experimental
description: Patients will receive continuous helmet pressure support ventilation for at least 16 hours/day the first 2 calendar days. Continuous noninvasive ventilation without interruptions will be strongly encouraged in the first 24 hours of treatment. The ventilator will be set in pressure support mode. Use of continuous positive airway pressure by flow generators and Venturi systems instead of pressure support ventilation will be allowed in case of shortage of ventilators. Maintenance of positive end-expiratory pressure ≥ 8-10 during the treatment is mandatory.
After weaning and during any interruption from noninvasive ventilation, patients will undergo low-flow or high-flow oxygen, according to the decision of the attending physician.
The treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge.
intervention type: Device
intervention name: Noninvasive respiratory support
description: In both arms, the treatment according to the assigned protocol will be continued until the patient requires endotracheal intubation or (in case of no intubation) up to ICU discharge.
Patients will have to undergo the allocated treatment within 1 hour from the moment of randomization and within 24 hours from admission in the intensive care unit
arm group label: Helmet noninvasive ventilation
arm group label: High-flow nasal cannula
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Domenico Luca Grieco, MD
role: Principal Investigator
affiliation: Fondazione Policlinico A. Gemelli IRCCS
last name: Massimo Antonelli, MD
role: Study Director
affiliation: Fondazione Policlinico A. Gemelli IRCCS
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Respiratory Insufficiency
mesh term: Hypoxia
sharing ipd: Undecided
ipd description: Data will be made available upon a reasonable request