<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/NCT02213237</url>
  </required_header>
  <id_info>
    <org_study_id>201107031 RC</org_study_id>
    <nct_id>NCT02213237</nct_id>
  </id_info>
  <brief_title>The Application of SERS and Metabolomics in Sepsis</brief_title>
  <official_title>The Application of SERS and Metabolomics in Sepsis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It has always been a real challenge to treat sepsis in critically ill patients. The mortality&#xD;
      is as high as 20％ in patients with severe sepsis and 46％ with septic shock develops. Early&#xD;
      diagnosis and early treatment are the principles. Along with appropriate resuscitation,&#xD;
      judicious and thoughtful intravenous antibiotic therapy is the critical determinant of&#xD;
      survival in sepsis and septic shock given that ineffective initial therapy worsens the&#xD;
      outcome. Blood culture and subsequent susceptibility testing are the gold standard for&#xD;
      microbiological diagnosis to direct the optimal use of antibiotic. However, this conventional&#xD;
      approach usually takes 5-7 days to wait for the final report. Positive results were reported&#xD;
      in only 30% of patients with sepsis and 50 to 60% septic shock. Moreover, the very low&#xD;
      bacteria level in blood and prior use of antibiotics may prevent pathogen growth.&#xD;
      Surface-enhanced Raman scattering (SERS) is a novel spectroscopy technique based on Raman&#xD;
      scattering and localized surface plasma resonance (LSPR), which results in strongly enhanced&#xD;
      Raman signals derived from molecules attached to nanometre-sized gold (Au) and silver (Ag)&#xD;
      structures. SERS provides the structural information of biomedical molecules with&#xD;
      ultra-sensitive characterization down to single molecular level in fast and non-destructive&#xD;
      manner. The clinical application of SERS in sepsis will first help to recognize pathogens as&#xD;
      well as their specific drug sensitivity, and then optimally guide the initial antibiotics&#xD;
      usage. Plasma from twenty blood culture proven Gram positive, negative and Candida cases will&#xD;
      separately subject to metabolomics profiling and bioinformatics analysis to establish each&#xD;
      pathogen metabolites profile. The sensitivity and specificity of SERS and metabolomics in&#xD;
      identifying pathogen and antibiotics-resistant strains will be evaluated. The investigators&#xD;
      expected both techniques to play a crucial role in modern sepsis treatment and bring great&#xD;
      impact on mortality reduction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sepsis is a serious medical condition caused by an overwhelming immune response to infection.&#xD;
      Different series of chemicals released into the blood to fight infection trigger systemic&#xD;
      inflammation, which is also called systemic inflammatory syndrome, SIRS. Sepsis is one of the&#xD;
      major public health issues, which are characterized with high cost and high mortality.&#xD;
      Epidemiological studies suggest that there are approximately 300 sepsis cases in per 100,000&#xD;
      population; accounting for 2% of all hospital admissions and up to 30% of intensive care unit&#xD;
      admissions. Sepsis is the leading cause of death in critically ill patients. The mortality is&#xD;
      as high as 20％ in patients with severe sepsis and 46％ when septic shock develops. Despite&#xD;
      recent advances in sepsis treatment, including early goal-directed therapy, low-dose&#xD;
      corticosteroid use, protective ventilation, intensive glucose control and activated protein C&#xD;
      use, sepsis is still a major challenge for clinical physicians.&#xD;
&#xD;
      Early appropriate antibiotic therapy targeting at the causative pathogen is always crucial to&#xD;
      the successful treatment of severe sepsis and septic shock. However, blood culture, the&#xD;
      current standard for microbiological diagnosis, can't provide the instant information of&#xD;
      pathogens identification at the right beginning of sepsis.&#xD;
&#xD;
      It usually takes 5-7 days to wait for the final report and even much longer for some&#xD;
      slow-growth bacteria or yeasts. Moreover, the yield positive rate is low. Only 30% positive&#xD;
      results were reported in patients with sepsis and 50 to 60% in septic shock. Some&#xD;
      microorganisms are present in the blood in very small numbers and must have longer time to&#xD;
      reproduce and grow to quantities that can be detected. Some microorganisms are difficult to&#xD;
      grow and special nutrient media may be needed. Viruses cannot be also detected using blood&#xD;
      culture bottles designed to grow bacteria. Besides, antimicrobial therapy in the preceding&#xD;
      two weeks may prevent pathogen growth.&#xD;
&#xD;
      Since the time to initiation of appropriate antimicrobial therapy is the strongest predictor&#xD;
      of mortality, the antibiotics are usually started &quot;empirically&quot; (ie. based on doctors'&#xD;
      experience) with broad spectrum and adjusted according to the clinical response. For lack of&#xD;
      precise data, inadequate infection control may encounter leading to poor prognosis, and&#xD;
      furthermore adverse effects of antibiotics such as organ toxicity and collateral damage (i.&#xD;
      e., selection of drug-resistant organisms and the unwanted development of colonization or&#xD;
      infection with multidrug-resistant organisms) occurs.&#xD;
&#xD;
      Using the SERS and fluorescent microscopy-based high-speed diagnosis platform for clinical&#xD;
      microbiology may help to solve this problem. The specific aims of the subproject are listed&#xD;
      as below:&#xD;
&#xD;
        1. To develop a comprehensive protocol of pretreatment of the complex blood sample from the&#xD;
           patients with sepsis as the preparation for SERS detection.&#xD;
&#xD;
        2. To identify the causative bacteria or yeasts in the blood by the high-speed diagnosis&#xD;
           platform based on SERS to guide the initial antibiotics treatment in sepsis.&#xD;
&#xD;
        3. To examine the susceptibility of the causative pathogen to various antibiotics to guide&#xD;
           the initial antibiotics treatment in sepsis.&#xD;
&#xD;
        4. To quantify the bacterial counts in blood to explore the relationship between the load&#xD;
           (virulence) of pathogen and clinical course, transmissibility, and antibiotic resistance&#xD;
           in patients with sepsis.&#xD;
&#xD;
        5. To compile a database of SERS spectra of clinical microbiology, including bacteria,&#xD;
           yeasts and fungi that are the common causative pathogens of sepsis.&#xD;
&#xD;
      The investigators expect this novel technique based on SERS and fluorescent optical&#xD;
      microscopy will play a crucial role in modern sepsis treatment, not only bringing great&#xD;
      impact on mortality reduction, cost control, but also alleviating the problem of growing&#xD;
      resistant trains from the inappropriate use of antibiotics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2011</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Identification of the causal pathogenic organism of sepsis subjects as well as the drug sensitivity test by SERS technique.</measure>
    <time_frame>5-6 hours</time_frame>
    <description>By the SERS technique may measure one time as below:&#xD;
Reducing detect/diagnosis time of bacteria or yeasts about blood sample of clinical sepsis subjects within one day.&#xD;
Reducing detect/diagnosis time of bacteria or yeasts for the drug sensitivity test of sepsis subjects within one day.</description>
  </primary_outcome>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Sepsis</condition>
  <eligibility>
    <study_pop>
      <textblock>
        hospitalized patient with Septic shock&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Any hospitalized patient with&#xD;
&#xD;
          -  Septic shock&#xD;
&#xD;
          -  Before the use of parenteral or systemic antimicrobial therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Organ transplantation&#xD;
&#xD;
          -  Cancer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yin-Yi Han, MD</last_name>
    <role>Study Chair</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yin-Yi Han, MD</last_name>
    <phone>+886-9-72651405</phone>
    <email>Noviahan@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yin-Yi Han, MD</last_name>
      <phone>+886-9-72651405</phone>
      <email>Noviahan@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>October 11, 2013</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 11, 2014</study_first_posted>
  <last_update_submitted>December 12, 2016</last_update_submitted>
  <last_update_submitted_qc>December 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 14, 2016</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>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
  </condition_browse>
  <!-- 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/NCT02213237
org study id: 201107031 RC
nct id: NCT02213237
lead sponsor: 
has dmc: Yes
It has always been a real challenge to treat sepsis in critically ill patients. The mortality
      is as high as 20％ in patients with severe sepsis and 46％ with septic shock develops. Early
      diagnosis and early treatment are the principles. Along with appropriate resuscitation,
      judicious and thoughtful intravenous antibiotic therapy is the critical determinant of
      survival in sepsis and septic shock given that ineffective initial therapy worsens the
      outcome. Blood culture and subsequent susceptibility testing are the gold standard for
      microbiological diagnosis to direct the optimal use of antibiotic. However, this conventional
      approach usually takes 5-7 days to wait for the final report. Positive results were reported
      in only 30% of patients with sepsis and 50 to 60% septic shock. Moreover, the very low
      bacteria level in blood and prior use of antibiotics may prevent pathogen growth.
      Surface-enhanced Raman scattering (SERS) is a novel spectroscopy technique based on Raman
      scattering and localized surface plasma resonance (LSPR), which results in strongly enhanced
      Raman signals derived from molecules attached to nanometre-sized gold (Au) and silver (Ag)
      structures. SERS provides the structural information of biomedical molecules with
      ultra-sensitive characterization down to single molecular level in fast and non-destructive
      manner. The clinical application of SERS in sepsis will first help to recognize pathogens as
      well as their specific drug sensitivity, and then optimally guide the initial antibiotics
      usage. Plasma from twenty blood culture proven Gram positive, negative and Candida cases will
      separately subject to metabolomics profiling and bioinformatics analysis to establish each
      pathogen metabolites profile. The sensitivity and specificity of SERS and metabolomics in
      identifying pathogen and antibiotics-resistant strains will be evaluated. The investigators
      expected both techniques to play a crucial role in modern sepsis treatment and bring great
      impact on mortality reduction.
Sepsis is a serious medical condition caused by an overwhelming immune response to infection.
      Different series of chemicals released into the blood to fight infection trigger systemic
      inflammation, which is also called systemic inflammatory syndrome, SIRS. Sepsis is one of the
      major public health issues, which are characterized with high cost and high mortality.
      Epidemiological studies suggest that there are approximately 300 sepsis cases in per 100,000
      population; accounting for 2% of all hospital admissions and up to 30% of intensive care unit
      admissions. Sepsis is the leading cause of death in critically ill patients. The mortality is
      as high as 20％ in patients with severe sepsis and 46％ when septic shock develops. Despite
      recent advances in sepsis treatment, including early goal-directed therapy, low-dose
      corticosteroid use, protective ventilation, intensive glucose control and activated protein C
      use, sepsis is still a major challenge for clinical physicians.

      Early appropriate antibiotic therapy targeting at the causative pathogen is always crucial to
      the successful treatment of severe sepsis and septic shock. However, blood culture, the
      current standard for microbiological diagnosis, can't provide the instant information of
      pathogens identification at the right beginning of sepsis.

      It usually takes 5-7 days to wait for the final report and even much longer for some
      slow-growth bacteria or yeasts. Moreover, the yield positive rate is low. Only 30% positive
      results were reported in patients with sepsis and 50 to 60% in septic shock. Some
      microorganisms are present in the blood in very small numbers and must have longer time to
      reproduce and grow to quantities that can be detected. Some microorganisms are difficult to
      grow and special nutrient media may be needed. Viruses cannot be also detected using blood
      culture bottles designed to grow bacteria. Besides, antimicrobial therapy in the preceding
      two weeks may prevent pathogen growth.

      Since the time to initiation of appropriate antimicrobial therapy is the strongest predictor
      of mortality, the antibiotics are usually started "empirically" (ie. based on doctors'
      experience) with broad spectrum and adjusted according to the clinical response. For lack of
      precise data, inadequate infection control may encounter leading to poor prognosis, and
      furthermore adverse effects of antibiotics such as organ toxicity and collateral damage (i.
      e., selection of drug-resistant organisms and the unwanted development of colonization or
      infection with multidrug-resistant organisms) occurs.

      Using the SERS and fluorescent microscopy-based high-speed diagnosis platform for clinical
      microbiology may help to solve this problem. The specific aims of the subproject are listed
      as below:

        1. To develop a comprehensive protocol of pretreatment of the complex blood sample from the
           patients with sepsis as the preparation for SERS detection.

        2. To identify the causative bacteria or yeasts in the blood by the high-speed diagnosis
           platform based on SERS to guide the initial antibiotics treatment in sepsis.

        3. To examine the susceptibility of the causative pathogen to various antibiotics to guide
           the initial antibiotics treatment in sepsis.

        4. To quantify the bacterial counts in blood to explore the relationship between the load
           (virulence) of pathogen and clinical course, transmissibility, and antibiotic resistance
           in patients with sepsis.

        5. To compile a database of SERS spectra of clinical microbiology, including bacteria,
           yeasts and fungi that are the common causative pathogens of sepsis.

      The investigators expect this novel technique based on SERS and fluorescent optical
      microscopy will play a crucial role in modern sepsis treatment, not only bringing great
      impact on mortality reduction, cost control, but also alleviating the problem of growing
      resistant trains from the inappropriate use of antibiotics.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Identification of the causal pathogenic organism of sepsis subjects as well as the drug sensitivity test by SERS technique.
time frame: 5-6 hours
description: By the SERS technique may measure one time as below:
Reducing detect/diagnosis time of bacteria or yeasts about blood sample of clinical sepsis subjects within one day.
Reducing detect/diagnosis time of bacteria or yeasts for the drug sensitivity test of sepsis subjects within one day.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Yin-Yi Han, MD
role: Study Chair
affiliation: National Taiwan University Hospital
last name: Yin-Yi Han, MD
phone: +886-9-72651405
email: Noviahan@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia