<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/NCT04452708</url>
  </required_header>
  <id_info>
    <org_study_id>2020.203</org_study_id>
    <nct_id>NCT04452708</nct_id>
  </id_info>
  <brief_title>HFNC and NIV for COVID-19 Complicated by Respiratory Failure</brief_title>
  <official_title>The Safety of High Flow Nasal Cannula and Noninvasive Ventilation for Treatment of Patients With COVID-19 Complicated by Respiratory Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Health and Medical Research Fund</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Chinese University of Hong Kong</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Patients with COVID-19 have a range of clinical spectrum from asymptomatic&#xD;
      infection, mild illness, moderate infection requiring supplemental oxygen and severe&#xD;
      infection requiring intensive care support. High flow nasal cannula (HFNC) oxygen therapy and&#xD;
      noninvasive ventilation (NIV) may offer respiratory support to patients with COVID-19&#xD;
      complicated by acute hypoxemic respiratory failure if conventional oxygen therapy (COT) fails&#xD;
      to maintain satisfactory oxygenation but whether these respiratory therapies would lead to&#xD;
      airborne viral transmission is unknown.&#xD;
&#xD;
      Aims: This study examines whether SARS-2 virus can be detected in small particles in the&#xD;
      hospital isolation rooms in patients who receive a) HFNC, b) NIV via oronasal masks and c)&#xD;
      conventional nasal cannula for respiratory failure.&#xD;
&#xD;
      Method: A field test to be performed at the Prince of Wales hospital ward 12C single bed&#xD;
      isolation room with 12 air changes/hr on patients (n=5 for each category of respiratory&#xD;
      therapy) with confirmed COVID-19 who require treatment for respiratory failure with a) HFNC&#xD;
      up to 60L/min, b) NIV via oronasal masks and c) conventional nasal cannula up to 5L/min of&#xD;
      oxygen. While the patient is on respiratory support, we would position 3 stationary devices&#xD;
      in the isolation room (one next to each side of the bed and another at the end of the bed) of&#xD;
      the patient with confirmed COVID-19 infection, and sample the air for four hours&#xD;
      continuously.&#xD;
&#xD;
      Results &amp; implications: If air sampling RTPCR and viral culture is positive, this would&#xD;
      objectively confirm that HFNC and NIV require airborne precaution by healthcare workers&#xD;
      during application.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A novel coronavirus, subsequently named by the World Health Organization (WHO) as severe&#xD;
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as the cause of atypical&#xD;
      pneumonia linked to a seafood market in Wuhan, China in Dec 2019. Since then, SARS-CoV-2&#xD;
      related-disease (named COVID-19 by the WHO), has spread internationally to the scale of a&#xD;
      global pandemic. Although most patients present with mild respiratory symptoms, some have&#xD;
      severe pneumonia and a small proportion may become critically ill. Severe COVID-19 disease&#xD;
      often progresses to acute hypoxemic respiratory failure requiring high fractional&#xD;
      concentration of inspired oxygen (FiO2) and consideration for non-invasive ventilation (NIV)&#xD;
      strategies.&#xD;
&#xD;
      High-flow nasal cannula (HFNC) has emerged as a non-invasive strategy improving oxygenation&#xD;
      and carbon dioxide clearance by, in comparisons to other NIV strategies, better matching&#xD;
      patients' inspiratory demands by delivering up to 60 L/min of gas flow and FiO2 up to 1.0. A&#xD;
      systematic review found low certainty evidence suggesting benefit of HFNC in reducing the&#xD;
      need for invasive mechanical ventilation (IMV) or escalation of oxygen therapy compared to&#xD;
      conventional oxygen therapy (COT), and moderate certainty evidence suggesting no large&#xD;
      difference in mortality. HFNC may reduce the need for IMV and associated complications such&#xD;
      as ventilator-associated pneumonias, and alleviate the strain on healthcare systems during&#xD;
      the COVID-19 pandemic.&#xD;
&#xD;
      COVID-19 spreads predominantly through respiratory droplets and fomites. There is concern,&#xD;
      however, that airborne transmission may occur during respiratory procedures that generate&#xD;
      aerosols. Airborne transmission involves smaller particles, typically &lt;5μm in diameter, which&#xD;
      may remain suspended in the air for extended periods of time, transmitted over distances&#xD;
      greater than 1m, and inhaled into the lower airways. Reduction of respiratory particles to &lt;5&#xD;
      µm involves evaporation of larger droplets and their contained organisms, and rehydration&#xD;
      after deposition into the airway; therefore, airborne transmission is organism-specific, and&#xD;
      requires the organism to survive a process of desiccation and aerosolization in sufficient&#xD;
      numbers to cause infection. SARS-CoV2 has been shown to survive in air for 3 hrs after&#xD;
      deliberate aerolization.&#xD;
&#xD;
      The Surviving Sepsis Campaign (SSC) COVID-19 guidelines provide a weak recommendation for the&#xD;
      preferential use of HFNC over other NIV strategies in patients refractory to COT for type 1&#xD;
      respiratory failure.10 The use of high flow rates raises concerns that HFNC may cause&#xD;
      aerosolization of infectious particles. Using a human patient simulator and smoke particles&#xD;
      as markers visualized by a laser light sheet, HFNC with humidification may disperse exhaled&#xD;
      air up to 172mm upward and 620mm laterally when the nasal cannula is clipped on properly and&#xD;
      loosely respectively. Using the same methodology, NIV via the old generation oronasal masks&#xD;
      could disperse exhaled air diffusely but there is limited exhaled air dispersion through the&#xD;
      new generation masks with better design of the exhalation ports. In contrast, exhaled air&#xD;
      dispersion from conventional nasal cannula delivering oxygen at 5L/min without humidification&#xD;
      may disperse exhaled air to 1m towards the end of the bed.&#xD;
&#xD;
      Due to lack of field data on the use of these respiratory therapies in patients with COVID-19&#xD;
      complicated by respiratory failure, the role of fine particle aerosols in transmission of&#xD;
      viral infection during application of HFNC and NIV is unknown. Because of uncertainty around&#xD;
      the potential for aerosolization, the WHO has recommended that HFNC, NIV, including bubble&#xD;
      CPAP, should be used with airborne precautions until further evaluation of safety can be&#xD;
      completed. To alleviate concern by the healthcare workers in delivering these respiratory&#xD;
      therapies to patients with COVID-19 complicated by respiratory failure, it is important to&#xD;
      conduct a field test using viral samplers in patients with COVID-19 who require these&#xD;
      therapies for respiratory failure.&#xD;
&#xD;
      Aims and objectives This study aims to detect whether SARS-2 virus can be detected in small&#xD;
      particles in the hospital isolation rooms in patients who receive a) HFNC up to 60L/min, b)&#xD;
      NIV via oronasal masks and c) conventional nasal cannula.&#xD;
&#xD;
      Subjects and indications of respiratory therapy:&#xD;
&#xD;
      This is a field test to be performed at the Prince of Wales hospital ward 12C single bed&#xD;
      isolation room with 12 air changes per hr on patients (n=5 for each category of respiratory&#xD;
      therapy) with confirmed COVID-19 who require treatment for respiratory failure with a) HFNC&#xD;
      up to 60L/min, b) NIV via oronasal masks and c) conventional nasal cannula up to 5L/min of&#xD;
      oxygen. Five patients in each treatment category will be recruited as the majority (80%) of&#xD;
      confirmed cases in HK have been mild without respiratory failure. For example, among the 974&#xD;
      cases as of 10 April 2020, 23 and 25 patients respectively have ever required supplemental&#xD;
      oxygen at least 3L/min on the isolation wards and ICU support (for IMV, ECMO or shock).&#xD;
      Different respiratory therapy will be decided by the physician on duty for patients with&#xD;
      different degree of respiratory failure. In general, conventional nasal cannula is used for&#xD;
      mild respiratory failure while HFNC is required to those who remain hypoxic. NIV is usually&#xD;
      applied for those with type 2 respiratory failure. In adults with COVID-19, the SSC&#xD;
      Guidelines suggest starting supplemental oxygen if the peripheral oxygen saturation (SPO2) is&#xD;
      &lt; 92% (weak recommendation, low quality evidence), and recommend starting supplemental oxygen&#xD;
      if SpO2 is &lt; 90% (strong recommendation, moderate quality evidence) to achieve SpO2 not&#xD;
      higher than 96%. For adults with COVID-19 and acute hypoxemic respiratory failure despite&#xD;
      COT, the SSC guidelines suggest using HFNC over NIV (weak recommendation, low quality&#xD;
      evidence). In adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not&#xD;
      available and there is no urgent indication for endotracheal intubation, the SSC guidelines&#xD;
      suggest a trial of NIV with close monitoring and short-interval assessment for worsening of&#xD;
      respiratory failure (weak recommendation, very low quality evidence).&#xD;
&#xD;
      Respiratory therapy: COT with nasal cannula 1-5L/min of oxygen will be used to maintain SpO2&#xD;
      around 95% for patients with type 1 respiratory failure. If this is not achievable despite&#xD;
      5L/min of oxygen, HFNC at 50-60L/min with humidification at 37C (Airvo 2, Fisher &amp; Paykel,&#xD;
      Auckland, New Zealand) will be applied while NIV (Respironics V60) via oronasal mask&#xD;
      (Quattro, ResMed) will be reserved for patients with type 2 respiratory failure.&#xD;
&#xD;
      Air samplings:&#xD;
&#xD;
      On each air sampling period while the patient is on respiratory support, we would position 3&#xD;
      stationary devices in the isolation room (one next to each side of the bed and another at the&#xD;
      end of the bed) of the patient with confirmed COVID-19 infection, and sample the air for four&#xD;
      hours continuously. The National Institute for Occupational Safety and Health (NIOSH) device&#xD;
      consists of a three-stage cyclone air samplers set at height 1.5m and 1.0m, which represent&#xD;
      the mouth heights of a standing and sitting adult respectively and a meter that records&#xD;
      temperature and relative humidity (at height 1.3m) every four minutes. The NIOSH samplers are&#xD;
      located around the sampling bed ('Centre'), on the side of the sampling bed ('Side'), or&#xD;
      relocated during the period of the sampling. The NIOSH samplers are placed in the range of&#xD;
      0.5-1m (when placed next to the sampling bed) to 2-2.5m from the patient's head when placed&#xD;
      at the end of the bed.&#xD;
&#xD;
      Air is collected at 3.5L/minute into three size fractions: &gt;4μm (collected in a 15ml tube),&#xD;
      1-4μm (1.5ml tube) and &lt;1μm (by a polytetrafluoroethylene (PTFE) membrane filter with 3.0μm&#xD;
      pore size). For five sampling runs, an extra air sampler (set at height 0.8m) unconnected to&#xD;
      a pump will be added to the device as a negative control. After each collection, the 15ml and&#xD;
      1.5ml tubes are detached and 1 ml of viral transport medium (VTM) are added. The filter is&#xD;
      removed and immersed in 1mL of VTM inside a 5ml tube. All the tubes are then transported to&#xD;
      the laboratory at 4°C, vortexed, and the VTM is aliquoted and stored at -80°C for subsequent&#xD;
      laboratory analysis by reverse-transcriptase-polymerase-chain-reaction (RT-PCR). New sampling&#xD;
      tubes and filters are used and the samplers and other equipment are disinfected between uses.&#xD;
      The tripod, air tubing, sound-proof box and the meter are disinfected with Med-Clean (M&amp;W&#xD;
      International Ltd., Hong Kong), the NIOSH air samplers with 1% Virkon and 2% Citranox&#xD;
      (Alconox Inc, NY, USA), and the filter cassettes are autoclaved.&#xD;
&#xD;
      Viral loads:&#xD;
&#xD;
      Viral loads will be measured from the patient's upper respiratory tract (nasopharyngeal&#xD;
      flocked swab and throat swab) on admission and serially second daily during hospitalization&#xD;
      by means of quantitative RT-PCR assay with primers and probes targeting the N and Orf1b genes&#xD;
      of SARS-CoV-2.&#xD;
&#xD;
      Data processing and analysis:&#xD;
&#xD;
      Statistical analysis: Dependent variables are identified as the nasopharyngeal flocked swab&#xD;
      and throat swab viral load (log10 copies/mL) and detection of viral RNA from one or more&#xD;
      participant air samples (positive) vs. all negative air samples. The Wilcoxon-Mann-Whitney,&#xD;
      Kruskal Wallis tests and Spearman correlation are used to assess the presence of&#xD;
      statistically significant correlations or distributions between independent variables and the&#xD;
      upper respiratory tract swab viral load, while the Wilcoxon-Mann-Whitney and Fisher's exact&#xD;
      tests are used for air samples. Statistical analysis was performed using SAS University&#xD;
      Edition (SAS Institute, Cary, NC, USA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 11, 2020</start_date>
  <completion_date type="Actual">April 30, 2022</completion_date>
  <primary_completion_date type="Actual">April 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>detection of viral RNA from one or more participants' air samples</measure>
    <time_frame>within 4 hours after starting respiratory therapy</time_frame>
    <description>quantitative RTPCR from air samples</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the nasopharyngeal flocked swab and throat swab viral load (log10 copies/mL)</measure>
    <time_frame>up to 2 weeks</time_frame>
    <description>quantitative RTPCR from upper airway swab</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">26</enrollment>
  <condition>Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>HFNC at 30-60L/min</arm_group_label>
    <description>HFNC at 50-60L/min with humidification at 37C (Airvo 2, Fisher &amp; Paykel, Auckland, New Zealand) will be applied for patients with moderate type 1 respiratory failure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NIV</arm_group_label>
    <description>NIV (Respironics V60) via oronasal mask (Quattro, ResMed) will be reserved for patients with type 2 respiratory failure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional nasal oxygen</arm_group_label>
    <description>Oxygen 1-5 L/min via nasal cannula for those with mild type 1 respiratory failure</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>HFNC</intervention_name>
    <description>HFNV vs NIV vs conventional nasal cannula</description>
    <arm_group_label>HFNC at 30-60L/min</arm_group_label>
    <other_name>NIV</other_name>
    <other_name>Conventional nasal cannula</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      NIOSH air samplers are located around the sampling bed ('Centre'), on the side of the&#xD;
      sampling bed ('Side'), or relocated during the period of the sampling and application of each&#xD;
      respiratory therapy. Air is collected at 3.5L/minute into three size fractions: &gt;4μm&#xD;
      (collected in a 15ml tube), 1-4μm (1.5ml tube) and &lt;1μm (by a polytetrafluoroethylene (PTFE)&#xD;
      membrane filter with 3.0μm pore size). All the tubes are then transported to the laboratory&#xD;
      at 4°C, vortexed, and the VTM is aliquoted and stored at -80°C for subsequent laboratory&#xD;
      analysis by RT-PCR. Viral loads will be measured from the patient's upper respiratory tract&#xD;
      (nasopharyngeal flocked swab and throat swab) on admission and serially second daily during&#xD;
      hospitalization by means of quantitative RT-PCR assay.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This is a field test being conducted at the Prince of Wales hospital ward 12C single bed&#xD;
        isolation room with 12 air changes per hr on patients (n=5 for each category of respiratory&#xD;
        therapy) with confirmed COVID-19 who require treatment for respiratory failure with a) HFNC&#xD;
        up to 60L/min, b) NIV via oronasal masks and c) conventional nasal cannula up to 5L/min of&#xD;
        oxygen. Five patients in each treatment category will be recruited as the majority (80%) of&#xD;
        confirmed cases in HK have been mild without respiratory failure.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria: Patients with confirmed COVID-19 who require treatment for respiratory&#xD;
        failure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  inability to provide consent;&#xD;
&#xD;
          -  severe respiratory failure requiring invasive ventilatory support;&#xD;
&#xD;
          -  septic shock&#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>David S Hui, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>July 21, 2022</last_update_submitted>
  <last_update_submitted_qc>July 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Prof David Shu Cheong Hui</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>HFNC</keyword>
  <keyword>NIV</keyword>
  <keyword>oxygen</keyword>
  <keyword>COVID-19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Depending on the results</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04452708
org study id: 2020.203
nct id: NCT04452708
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Background: Patients with COVID-19 have a range of clinical spectrum from asymptomatic
      infection, mild illness, moderate infection requiring supplemental oxygen and severe
      infection requiring intensive care support. High flow nasal cannula (HFNC) oxygen therapy and
      noninvasive ventilation (NIV) may offer respiratory support to patients with COVID-19
      complicated by acute hypoxemic respiratory failure if conventional oxygen therapy (COT) fails
      to maintain satisfactory oxygenation but whether these respiratory therapies would lead to
      airborne viral transmission is unknown.

      Aims: This study examines whether SARS-2 virus can be detected in small particles in the
      hospital isolation rooms in patients who receive a) HFNC, b) NIV via oronasal masks and c)
      conventional nasal cannula for respiratory failure.

      Method: A field test to be performed at the Prince of Wales hospital ward 12C single bed
      isolation room with 12 air changes/hr on patients (n=5 for each category of respiratory
      therapy) with confirmed COVID-19 who require treatment for respiratory failure with a) HFNC
      up to 60L/min, b) NIV via oronasal masks and c) conventional nasal cannula up to 5L/min of
      oxygen. While the patient is on respiratory support, we would position 3 stationary devices
      in the isolation room (one next to each side of the bed and another at the end of the bed) of
      the patient with confirmed COVID-19 infection, and sample the air for four hours
      continuously.

      Results & implications: If air sampling RTPCR and viral culture is positive, this would
      objectively confirm that HFNC and NIV require airborne precaution by healthcare workers
      during application.
A novel coronavirus, subsequently named by the World Health Organization (WHO) as severe
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as the cause of atypical
      pneumonia linked to a seafood market in Wuhan, China in Dec 2019. Since then, SARS-CoV-2
      related-disease (named COVID-19 by the WHO), has spread internationally to the scale of a
      global pandemic. Although most patients present with mild respiratory symptoms, some have
      severe pneumonia and a small proportion may become critically ill. Severe COVID-19 disease
      often progresses to acute hypoxemic respiratory failure requiring high fractional
      concentration of inspired oxygen (FiO2) and consideration for non-invasive ventilation (NIV)
      strategies.

      High-flow nasal cannula (HFNC) has emerged as a non-invasive strategy improving oxygenation
      and carbon dioxide clearance by, in comparisons to other NIV strategies, better matching
      patients' inspiratory demands by delivering up to 60 L/min of gas flow and FiO2 up to 1.0. A
      systematic review found low certainty evidence suggesting benefit of HFNC in reducing the
      need for invasive mechanical ventilation (IMV) or escalation of oxygen therapy compared to
      conventional oxygen therapy (COT), and moderate certainty evidence suggesting no large
      difference in mortality. HFNC may reduce the need for IMV and associated complications such
      as ventilator-associated pneumonias, and alleviate the strain on healthcare systems during
      the COVID-19 pandemic.

      COVID-19 spreads predominantly through respiratory droplets and fomites. There is concern,
      however, that airborne transmission may occur during respiratory procedures that generate
      aerosols. Airborne transmission involves smaller particles, typically <5μm in diameter, which
      may remain suspended in the air for extended periods of time, transmitted over distances
      greater than 1m, and inhaled into the lower airways. Reduction of respiratory particles to <5
      µm involves evaporation of larger droplets and their contained organisms, and rehydration
      after deposition into the airway; therefore, airborne transmission is organism-specific, and
      requires the organism to survive a process of desiccation and aerosolization in sufficient
      numbers to cause infection. SARS-CoV2 has been shown to survive in air for 3 hrs after
      deliberate aerolization.

      The Surviving Sepsis Campaign (SSC) COVID-19 guidelines provide a weak recommendation for the
      preferential use of HFNC over other NIV strategies in patients refractory to COT for type 1
      respiratory failure.10 The use of high flow rates raises concerns that HFNC may cause
      aerosolization of infectious particles. Using a human patient simulator and smoke particles
      as markers visualized by a laser light sheet, HFNC with humidification may disperse exhaled
      air up to 172mm upward and 620mm laterally when the nasal cannula is clipped on properly and
      loosely respectively. Using the same methodology, NIV via the old generation oronasal masks
      could disperse exhaled air diffusely but there is limited exhaled air dispersion through the
      new generation masks with better design of the exhalation ports. In contrast, exhaled air
      dispersion from conventional nasal cannula delivering oxygen at 5L/min without humidification
      may disperse exhaled air to 1m towards the end of the bed.

      Due to lack of field data on the use of these respiratory therapies in patients with COVID-19
      complicated by respiratory failure, the role of fine particle aerosols in transmission of
      viral infection during application of HFNC and NIV is unknown. Because of uncertainty around
      the potential for aerosolization, the WHO has recommended that HFNC, NIV, including bubble
      CPAP, should be used with airborne precautions until further evaluation of safety can be
      completed. To alleviate concern by the healthcare workers in delivering these respiratory
      therapies to patients with COVID-19 complicated by respiratory failure, it is important to
      conduct a field test using viral samplers in patients with COVID-19 who require these
      therapies for respiratory failure.

      Aims and objectives This study aims to detect whether SARS-2 virus can be detected in small
      particles in the hospital isolation rooms in patients who receive a) HFNC up to 60L/min, b)
      NIV via oronasal masks and c) conventional nasal cannula.

      Subjects and indications of respiratory therapy:

      This is a field test to be performed at the Prince of Wales hospital ward 12C single bed
      isolation room with 12 air changes per hr on patients (n=5 for each category of respiratory
      therapy) with confirmed COVID-19 who require treatment for respiratory failure with a) HFNC
      up to 60L/min, b) NIV via oronasal masks and c) conventional nasal cannula up to 5L/min of
      oxygen. Five patients in each treatment category will be recruited as the majority (80%) of
      confirmed cases in HK have been mild without respiratory failure. For example, among the 974
      cases as of 10 April 2020, 23 and 25 patients respectively have ever required supplemental
      oxygen at least 3L/min on the isolation wards and ICU support (for IMV, ECMO or shock).
      Different respiratory therapy will be decided by the physician on duty for patients with
      different degree of respiratory failure. In general, conventional nasal cannula is used for
      mild respiratory failure while HFNC is required to those who remain hypoxic. NIV is usually
      applied for those with type 2 respiratory failure. In adults with COVID-19, the SSC
      Guidelines suggest starting supplemental oxygen if the peripheral oxygen saturation (SPO2) is
      < 92% (weak recommendation, low quality evidence), and recommend starting supplemental oxygen
      if SpO2 is < 90% (strong recommendation, moderate quality evidence) to achieve SpO2 not
      higher than 96%. For adults with COVID-19 and acute hypoxemic respiratory failure despite
      COT, the SSC guidelines suggest using HFNC over NIV (weak recommendation, low quality
      evidence). In adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not
      available and there is no urgent indication for endotracheal intubation, the SSC guidelines
      suggest a trial of NIV with close monitoring and short-interval assessment for worsening of
      respiratory failure (weak recommendation, very low quality evidence).

      Respiratory therapy: COT with nasal cannula 1-5L/min of oxygen will be used to maintain SpO2
      around 95% for patients with type 1 respiratory failure. If this is not achievable despite
      5L/min of oxygen, HFNC at 50-60L/min with humidification at 37C (Airvo 2, Fisher & Paykel,
      Auckland, New Zealand) will be applied while NIV (Respironics V60) via oronasal mask
      (Quattro, ResMed) will be reserved for patients with type 2 respiratory failure.

      Air samplings:

      On each air sampling period while the patient is on respiratory support, we would position 3
      stationary devices in the isolation room (one next to each side of the bed and another at the
      end of the bed) of the patient with confirmed COVID-19 infection, and sample the air for four
      hours continuously. The National Institute for Occupational Safety and Health (NIOSH) device
      consists of a three-stage cyclone air samplers set at height 1.5m and 1.0m, which represent
      the mouth heights of a standing and sitting adult respectively and a meter that records
      temperature and relative humidity (at height 1.3m) every four minutes. The NIOSH samplers are
      located around the sampling bed ('Centre'), on the side of the sampling bed ('Side'), or
      relocated during the period of the sampling. The NIOSH samplers are placed in the range of
      0.5-1m (when placed next to the sampling bed) to 2-2.5m from the patient's head when placed
      at the end of the bed.

      Air is collected at 3.5L/minute into three size fractions: >4μm (collected in a 15ml tube),
      1-4μm (1.5ml tube) and <1μm (by a polytetrafluoroethylene (PTFE) membrane filter with 3.0μm
      pore size). For five sampling runs, an extra air sampler (set at height 0.8m) unconnected to
      a pump will be added to the device as a negative control. After each collection, the 15ml and
      1.5ml tubes are detached and 1 ml of viral transport medium (VTM) are added. The filter is
      removed and immersed in 1mL of VTM inside a 5ml tube. All the tubes are then transported to
      the laboratory at 4°C, vortexed, and the VTM is aliquoted and stored at -80°C for subsequent
      laboratory analysis by reverse-transcriptase-polymerase-chain-reaction (RT-PCR). New sampling
      tubes and filters are used and the samplers and other equipment are disinfected between uses.
      The tripod, air tubing, sound-proof box and the meter are disinfected with Med-Clean (M&W
      International Ltd., Hong Kong), the NIOSH air samplers with 1% Virkon and 2% Citranox
      (Alconox Inc, NY, USA), and the filter cassettes are autoclaved.

      Viral loads:

      Viral loads will be measured from the patient's upper respiratory tract (nasopharyngeal
      flocked swab and throat swab) on admission and serially second daily during hospitalization
      by means of quantitative RT-PCR assay with primers and probes targeting the N and Orf1b genes
      of SARS-CoV-2.

      Data processing and analysis:

      Statistical analysis: Dependent variables are identified as the nasopharyngeal flocked swab
      and throat swab viral load (log10 copies/mL) and detection of viral RNA from one or more
      participant air samples (positive) vs. all negative air samples. The Wilcoxon-Mann-Whitney,
      Kruskal Wallis tests and Spearman correlation are used to assess the presence of
      statistically significant correlations or distributions between independent variables and the
      upper respiratory tract swab viral load, while the Wilcoxon-Mann-Whitney and Fisher's exact
      tests are used for air samples. Statistical analysis was performed using SAS University
      Edition (SAS Institute, Cary, NC, USA).
observational model: Cohort
time perspective: Prospective
measure: detection of viral RNA from one or more participants' air samples
time frame: within 4 hours after starting respiratory therapy
description: quantitative RTPCR from air samples
measure: the nasopharyngeal flocked swab and throat swab viral load (log10 copies/mL)
time frame: up to 2 weeks
description: quantitative RTPCR from upper airway swab
arm group label: HFNC at 30-60L/min
description: HFNC at 50-60L/min with humidification at 37C (Airvo 2, Fisher & Paykel, Auckland, New Zealand) will be applied for patients with moderate type 1 respiratory failure
arm group label: NIV
description: NIV (Respironics V60) via oronasal mask (Quattro, ResMed) will be reserved for patients with type 2 respiratory failure
arm group label: Conventional nasal oxygen
description: Oxygen 1-5 L/min via nasal cannula for those with mild type 1 respiratory failure
intervention type: Device
intervention name: HFNC
description: HFNV vs NIV vs conventional nasal cannula
arm group label: HFNC at 30-60L/min
other name: NIV
other name: Conventional nasal cannula
NIOSH air samplers are located around the sampling bed ('Centre'), on the side of the
      sampling bed ('Side'), or relocated during the period of the sampling and application of each
      respiratory therapy. Air is collected at 3.5L/minute into three size fractions: >4μm
      (collected in a 15ml tube), 1-4μm (1.5ml tube) and <1μm (by a polytetrafluoroethylene (PTFE)
      membrane filter with 3.0μm pore size). All the tubes are then transported to the laboratory
      at 4°C, vortexed, and the VTM is aliquoted and stored at -80°C for subsequent laboratory
      analysis by RT-PCR. Viral loads will be measured from the patient's upper respiratory tract
      (nasopharyngeal flocked swab and throat swab) on admission and serially second daily during
      hospitalization by means of quantitative RT-PCR assay.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David S Hui, MD
role: Principal Investigator
affiliation: Chinese University of Hong Kong
facility: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Prof David Shu Cheong Hui
investigator title: Professor
mesh term: COVID-19
mesh term: Respiratory Insufficiency
sharing ipd: Undecided
ipd description: Depending on the results