<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/NCT04492943</url>
  </required_header>
  <id_info>
    <org_study_id>2020P001048</org_study_id>
    <nct_id>NCT04492943</nct_id>
  </id_info>
  <brief_title>To Observe Whether Isoflurane Can Treat COVID-19 Patients</brief_title>
  <official_title>To Observe Whether Isoflurane Can Treat COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a blood collection and retrospective data collection study. The investigators plan to&#xD;
      assess whether the sedative drug, isoflurane, can treat COVID-19 patients relatively better&#xD;
      compared to other sedative drugs given during routine treatment to patients on mechanical&#xD;
      ventilation. The investigators will also use nanoneedle biosensors to quickly detect blood&#xD;
      IgM/IgG ratio in those patients, and (3) to establish a pre-clinical system to determine the&#xD;
      effects of inhalational anesthetics on amounts of SARS-CoV-2 and other viruses, and&#xD;
      pneumoniae.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are neither effective treatments nor fast detection for COVID-19. Here the&#xD;
      investigators propose a medical records and excess clinical material study to determine&#xD;
      whether anesthetic isoflurane can treat COVID-19. Specifically, inhalation anesthetics,&#xD;
      including isoflurane, inhibit the replication of an RNA virus. In addition, anesthesia&#xD;
      machines have been used to provide mechanical ventilation for COVID-19 patients at MGH and at&#xD;
      other hospitals. Finally, due to the shortage of intravenous anesthetic propofol, inhalation&#xD;
      anesthetics including isoflurane, delivered by the anesthesia machine, are currently used to&#xD;
      sedate COVID-19 patients during mechanic ventilation. Moreover, isoflurane is very&#xD;
      economical, e.g. $6 (isoflurane) versus $1200 (propofol) per patient per day in sedating&#xD;
      COVID-19 patients. As such, the investigators propose to use this already established system&#xD;
      in COVID-19 patients to determine whether isoflurane, delivered to lungs, can treat COVID-19&#xD;
      and especially COVID-19 pneumonia. In summary, the proposed study is a low risk observation&#xD;
      research using the already established clinical care system of COVID-19 patients and the&#xD;
      investigators will NOT have any additional procedures required for research purpose. The&#xD;
      investigators will also collect the left-over clinical sample and then use nanotechnology to&#xD;
      achieve fast detection of IgM/IgG ratio as the biomarker of the progress of COVID-19&#xD;
      following the isoflurane or propofol sedation.&#xD;
&#xD;
      Specifically, inhalation anesthetics, including isoflurane, inhibit replication of the&#xD;
      measles virus and other RNA virus 1,2. Severe COVID-19 patients need mechanical ventilation&#xD;
      to support lung function. The anesthesia machine can be used to ventilate lungs in these&#xD;
      patients in addition to regular ventilators which has already been started at MGH and other&#xD;
      hospitals as regular ventilators are extremely limited. Clinicians have already determined&#xD;
      the settings of these machines, including humidification, for treating COVID-19 patients and&#xD;
      the investigators will use these predetermined settings in this study. Additionally, there is&#xD;
      a shortage of the intravenous anesthetic propofol. As a result, inhalation anesthetics&#xD;
      including isoflurane, delivered by the anesthesia machine, are currently used to sedate&#xD;
      COVID-19 patients during mechanic ventilation. Moreover, isoflurane is very economical, e.g.&#xD;
      $6 (isoflurane) versus $1200 (propofol) per patient per day in sedating COVID-19 patients. As&#xD;
      such, the investigators propose to use this already established system in COVID-19 patients&#xD;
      to determine whether isoflurane, delivered to lungs, can treat COVID-19 and especially&#xD;
      COVID-19 pneumonia better than other sedatives in this retrospective data collection study.&#xD;
      Moreover, in pre-clinical studies, the investigators propose to establish a system to&#xD;
      determine whether inhalation anesthetics can treat virus-induced pneumonia by reducing the&#xD;
      amount of virus, e.g., SARS-CoV-2 and influenza.&#xD;
&#xD;
      Sensitive, cost-effective and fast detection of SARS-CoV-2 is extremely critical. Currently,&#xD;
      a real-time polymerase chain reaction (PCR) test detects the genetic material of SARS-CoV-2.&#xD;
      However, the test has large false negatives, poses risks during specimen collection and&#xD;
      sample handling, and takes a long time (~ 8 hours). However, in response to SARS-CoV-2, IgG&#xD;
      is the most abundant immunoglobulin to be produced and is maintained in the body after&#xD;
      initial exposure for a long-term response. IgM is the first immunoglobulin to be produced but&#xD;
      is primarily detected during the early onset of disease. Therefore, SARS-CoV-2 specific&#xD;
      IgM/IgG ratio in blood could be used as biomarker for COVID-19 prognostics (Fatma et al,&#xD;
      medRxiv, 2020), and could also be used as a measure of drug response 3. The nanoneedle&#xD;
      technology developed at a startup-company from Harvard University (NanoMosaic LLC) provides&#xD;
      pg/ml-level sensitivity and 10 uL sample volume for quantification of a panel of biomarkers&#xD;
      including SARS-CoV-2 specific IgG and IgMs in a single assay. The technology uses nanoneedle&#xD;
      biosensors densely integrated on a silicon chip and manufactured with CMOS-compatible&#xD;
      nanofabrication processes 4. Each nanoneedle is a label-free biosensor and changes its&#xD;
      scattering spectrum when an antigen binds to its surface. Each analyte-specific sensing area&#xD;
      consists of a total of ~24k nanoneedles divided into a digital region (~20k nanoneedles), an&#xD;
      analog region (~3k nanoneedles) and a fabrication QC region (~1k nanoneedles), thus providing&#xD;
      a wider dynamic range beyond the digital counting concentration ranges. Each single analyte&#xD;
      area, including both digital and analog sensors, is less than 500 um. With further&#xD;
      development, the entire assay can be finished in a half-hour on a table-top instrument with&#xD;
      less than 10 ul blood samples, which will facilitate therapeutic development and decision&#xD;
      making for COVID-19 and other virus-induced pneumoniae.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 20, 2020</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Survival Outcome</measure>
    <time_frame>From the date of hospital admission until date of discharge or death of any cause, assessed up to 6 months.</time_frame>
    <description>Survival outcome will be based on whether the patient either (a) recovers from COVID-19 and is discharged from the hospital or (b) does not recover from COVID-19 and passes away while in the hospital.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>COVID-19 Testing Methods</measure>
    <time_frame>From the date of hospital admission until date of discharge or death of any cause, assessed up to 6 months.</time_frame>
    <description>Identifying faster COVID-19 testing methods, specifically nanoneedle biotechnology.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>COVID-19 Clearance</measure>
    <time_frame>From the date of hospital admission until date of discharge or death of any cause, assessed up to 6 months.</time_frame>
    <description>COVID-19 clearance will be based on whether the patient either (a) tests negative for COVID-19 after treatment in the hospital or (b) does not test negative for COVID-19 after treatment in the hospital.</description>
  </primary_outcome>
  <enrollment type="Actual">35</enrollment>
  <condition>COVID-19</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood may be collected from patients if available from excess clinical blood draws conducted&#xD;
      during routine clinical care.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        COVID-19 positive patients placed on mechanical ventilation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Over the age of 18 years old&#xD;
&#xD;
          -  Tested positive for COVID-19&#xD;
&#xD;
          -  Documented SARS-CoV-2 carriage in the nasopharyngeal sample by PCR&#xD;
&#xD;
          -  Intubated for mechanical ventilation with an anesthesia machine&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient or any their family members have any contraindication for inhalation&#xD;
             anesthetics (e.g., malignant hyperthermia).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02129-2020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>April 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>September 1, 2020</last_update_submitted>
  <last_update_submitted_qc>September 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Zhongcong Xie</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>Mechanical ventilation</keyword>
  <keyword>Anesthesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Participant data may be shared with other researches working on similar studies. The only identifiers in data sets that will be shared are (1) hospital admission dates (MM/DD/YYYY), ICU admission dates (MM/DD/YYYY), ICU discharge dates (MM/DD/YYYY), and hospital discharge dates (MM/DD/YYYY).</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/NCT04492943
org study id: 2020P001048
nct id: NCT04492943
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a blood collection and retrospective data collection study. The investigators plan to
      assess whether the sedative drug, isoflurane, can treat COVID-19 patients relatively better
      compared to other sedative drugs given during routine treatment to patients on mechanical
      ventilation. The investigators will also use nanoneedle biosensors to quickly detect blood
      IgM/IgG ratio in those patients, and (3) to establish a pre-clinical system to determine the
      effects of inhalational anesthetics on amounts of SARS-CoV-2 and other viruses, and
      pneumoniae.
There are neither effective treatments nor fast detection for COVID-19. Here the
      investigators propose a medical records and excess clinical material study to determine
      whether anesthetic isoflurane can treat COVID-19. Specifically, inhalation anesthetics,
      including isoflurane, inhibit the replication of an RNA virus. In addition, anesthesia
      machines have been used to provide mechanical ventilation for COVID-19 patients at MGH and at
      other hospitals. Finally, due to the shortage of intravenous anesthetic propofol, inhalation
      anesthetics including isoflurane, delivered by the anesthesia machine, are currently used to
      sedate COVID-19 patients during mechanic ventilation. Moreover, isoflurane is very
      economical, e.g. $6 (isoflurane) versus $1200 (propofol) per patient per day in sedating
      COVID-19 patients. As such, the investigators propose to use this already established system
      in COVID-19 patients to determine whether isoflurane, delivered to lungs, can treat COVID-19
      and especially COVID-19 pneumonia. In summary, the proposed study is a low risk observation
      research using the already established clinical care system of COVID-19 patients and the
      investigators will NOT have any additional procedures required for research purpose. The
      investigators will also collect the left-over clinical sample and then use nanotechnology to
      achieve fast detection of IgM/IgG ratio as the biomarker of the progress of COVID-19
      following the isoflurane or propofol sedation.

      Specifically, inhalation anesthetics, including isoflurane, inhibit replication of the
      measles virus and other RNA virus 1,2. Severe COVID-19 patients need mechanical ventilation
      to support lung function. The anesthesia machine can be used to ventilate lungs in these
      patients in addition to regular ventilators which has already been started at MGH and other
      hospitals as regular ventilators are extremely limited. Clinicians have already determined
      the settings of these machines, including humidification, for treating COVID-19 patients and
      the investigators will use these predetermined settings in this study. Additionally, there is
      a shortage of the intravenous anesthetic propofol. As a result, inhalation anesthetics
      including isoflurane, delivered by the anesthesia machine, are currently used to sedate
      COVID-19 patients during mechanic ventilation. Moreover, isoflurane is very economical, e.g.
      $6 (isoflurane) versus $1200 (propofol) per patient per day in sedating COVID-19 patients. As
      such, the investigators propose to use this already established system in COVID-19 patients
      to determine whether isoflurane, delivered to lungs, can treat COVID-19 and especially
      COVID-19 pneumonia better than other sedatives in this retrospective data collection study.
      Moreover, in pre-clinical studies, the investigators propose to establish a system to
      determine whether inhalation anesthetics can treat virus-induced pneumonia by reducing the
      amount of virus, e.g., SARS-CoV-2 and influenza.

      Sensitive, cost-effective and fast detection of SARS-CoV-2 is extremely critical. Currently,
      a real-time polymerase chain reaction (PCR) test detects the genetic material of SARS-CoV-2.
      However, the test has large false negatives, poses risks during specimen collection and
      sample handling, and takes a long time (~ 8 hours). However, in response to SARS-CoV-2, IgG
      is the most abundant immunoglobulin to be produced and is maintained in the body after
      initial exposure for a long-term response. IgM is the first immunoglobulin to be produced but
      is primarily detected during the early onset of disease. Therefore, SARS-CoV-2 specific
      IgM/IgG ratio in blood could be used as biomarker for COVID-19 prognostics (Fatma et al,
      medRxiv, 2020), and could also be used as a measure of drug response 3. The nanoneedle
      technology developed at a startup-company from Harvard University (NanoMosaic LLC) provides
      pg/ml-level sensitivity and 10 uL sample volume for quantification of a panel of biomarkers
      including SARS-CoV-2 specific IgG and IgMs in a single assay. The technology uses nanoneedle
      biosensors densely integrated on a silicon chip and manufactured with CMOS-compatible
      nanofabrication processes 4. Each nanoneedle is a label-free biosensor and changes its
      scattering spectrum when an antigen binds to its surface. Each analyte-specific sensing area
      consists of a total of ~24k nanoneedles divided into a digital region (~20k nanoneedles), an
      analog region (~3k nanoneedles) and a fabrication QC region (~1k nanoneedles), thus providing
      a wider dynamic range beyond the digital counting concentration ranges. Each single analyte
      area, including both digital and analog sensors, is less than 500 um. With further
      development, the entire assay can be finished in a half-hour on a table-top instrument with
      less than 10 ul blood samples, which will facilitate therapeutic development and decision
      making for COVID-19 and other virus-induced pneumoniae.
observational model: Cohort
time perspective: Retrospective
measure: Survival Outcome
time frame: From the date of hospital admission until date of discharge or death of any cause, assessed up to 6 months.
description: Survival outcome will be based on whether the patient either (a) recovers from COVID-19 and is discharged from the hospital or (b) does not recover from COVID-19 and passes away while in the hospital.
measure: COVID-19 Testing Methods
time frame: From the date of hospital admission until date of discharge or death of any cause, assessed up to 6 months.
description: Identifying faster COVID-19 testing methods, specifically nanoneedle biotechnology.
measure: COVID-19 Clearance
time frame: From the date of hospital admission until date of discharge or death of any cause, assessed up to 6 months.
description: COVID-19 clearance will be based on whether the patient either (a) tests negative for COVID-19 after treatment in the hospital or (b) does not test negative for COVID-19 after treatment in the hospital.
Blood may be collected from patients if available from excess clinical blood draws conducted
      during routine clinical care.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Zhongcong Xie
investigator title: Principle Investigator
mesh term: COVID-19
sharing ipd: Undecided
ipd description: Participant data may be shared with other researches working on similar studies. The only identifiers in data sets that will be shared are (1) hospital admission dates (MM/DD/YYYY), ICU admission dates (MM/DD/YYYY), ICU discharge dates (MM/DD/YYYY), and hospital discharge dates (MM/DD/YYYY).