<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/NCT03760315</url>
  </required_header>
  <id_info>
    <org_study_id>20181127</org_study_id>
    <nct_id>NCT03760315</nct_id>
  </id_info>
  <brief_title>mNGS vs Culture Critically Ill Patients</brief_title>
  <official_title>Department of Critical Care Medicine, Nanjing Zhong-Da Hospital, Southeast University School of Medicine,China;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Southeast University, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northern Jiangsu Province People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Southeast University, China</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>
      mNGS is popular in research and recently it has been used clinically to detect microbes in&#xD;
      the blood or other secretion in infected patients for quicker ,broad and accurate detection&#xD;
      of microbes. In ICU ,patients are critically ill and need quicker and accurate antibiotics&#xD;
      use to stop the pathologic process. The purpose of this study was to determine whether the&#xD;
      positive detection rate of pathogens in patients with sepsis by metagenomic full-targeted&#xD;
      detection technology was higher than that in blood culture, and to determine whether the&#xD;
      pathogens found in patients with sepsis by metagenomic full-targeted detection technology&#xD;
      were important for clinical development. Anti-infective regimens can help.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sepsis patients in ICU were took blood culture sample and blood sample for mNGS test (IDSeqTM&#xD;
      Ultra, Combing with Metagenomics and Pathogen/AMR/VF Probe Enrichment). Clinicians use their&#xD;
      knowledge and experience to decide antibiotics use with the guide of Culture results or mNGS&#xD;
      results. Validation with digital droplet PCR assays when metagenomic full-targeted assays&#xD;
      identify pathogens not identified in conventional blood cultures The difference between the&#xD;
      positive rate of mNGS and the positive rate of blood culture were recorded. Patient were&#xD;
      followed at least 28 days after enrollment or an outcome indicator. Possible scenarios for&#xD;
      detecting clinical impact were detected. Etiology, biochemical indicators, immune function,&#xD;
      infection indicator, secondary infection, SOFA score and length of stay，outcome were&#xD;
      recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2022</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 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>difference of positive rate between mNGS and Culture</measure>
    <time_frame>28 day</time_frame>
    <description>The difference between the positive rate of mNGS and the positive rate of blood culture.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The difference between the positive rate of metagenomic full capture technology and the Category of Clinical Impact</measure>
    <time_frame>28 day</time_frame>
    <description>Positive, Negative，None and Indeterminate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of SOFA</measure>
    <time_frame>7 day</time_frame>
    <description>change of SOFA score (include each organ) at baseline, day 3 and day 7 clinical improvement :Improvement in 2 or more clinical signs and symptoms no requirement for additional antibacterial treatment Clinical failure:Persistence or progression of baseline signs and symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>During hospitalization</time_frame>
    <description>28 day，ICU and hospital mortality Documented microbiologic eradication:Absence of primary microbe from infection site Presumed microbiologic eradication:Clinical cure without available microbiologic culture data Presumed microbiologic persistence:Clinical failure in the absence of any microbiologic data Documented microbiologic persistence:Continued presence of MRSA based on microbiologic culture Superinfection: Clinical failure and isolation of a pathogen not present at baseline at the original infection site</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay</measure>
    <time_frame>During hospitalization</time_frame>
    <description>ICU and hospital length of stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-infective treatment adjustment</measure>
    <time_frame>28 day</time_frame>
    <description>each Anti-infective treatment adjustment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>pathogen</measure>
    <time_frame>28 day</time_frame>
    <description>all the detect pathogens from mNGS and blood culture</description>
  </other_outcome>
  <other_outcome>
    <measure>secondary infection</measure>
    <time_frame>28 day</time_frame>
    <description>infection secondary to the primary infection</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Sepsis</arm_group_label>
    <description>All enrolled patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>blood mNGS (IDSeqTM Ultra); blood Culture</intervention_name>
    <description>take blood samples for mNGS and Culture at the same time in sepsis patients. No intervention on the treatment of the patients.</description>
    <arm_group_label>Sepsis</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA extracted from blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patient with sepsis and suspected bloodstream infection&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age &gt; 18years admit to ICU Meet the Sepsis 3.0 diagnostic criteria and suspected&#xD;
        bloodstream infection, and the diagnosis of Sepsis ≤ 24 hours; Estimated ICU stay ≥ 24&#xD;
        hours; Informed consent;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Severe organ dysfunction, expected death within 72 hours; Receive palliative care; Refuse&#xD;
        to participate;&#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>Haibo Qiu, MD</last_name>
    <role>Study Director</role>
    <affiliation>Southeast University, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>ling liu, MD</last_name>
    <phone>13851435472</phone>
    <email>liulingdoctor@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Nanjing Zhong-Da Hospital</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210009</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ling Liu, MD.</last_name>
      <phone>86-25-83272201</phone>
      <email>liulingdoctor@126.com</email>
    </contact>
    <contact_backup>
      <last_name>Haibo Qiu, PhD.,MD.</last_name>
      <phone>86-25-83272200</phone>
      <email>haiboq2000@yahoo.com.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Ling Liu, MD.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Southeast University, China</investigator_affiliation>
    <investigator_full_name>Ling Liu</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>next- generation sequencing； blood culture；IDSeqTM Ultra</keyword>
  <!-- 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/NCT03760315
org study id: 20181127
nct id: NCT03760315
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
mNGS is popular in research and recently it has been used clinically to detect microbes in
      the blood or other secretion in infected patients for quicker ,broad and accurate detection
      of microbes. In ICU ,patients are critically ill and need quicker and accurate antibiotics
      use to stop the pathologic process. The purpose of this study was to determine whether the
      positive detection rate of pathogens in patients with sepsis by metagenomic full-targeted
      detection technology was higher than that in blood culture, and to determine whether the
      pathogens found in patients with sepsis by metagenomic full-targeted detection technology
      were important for clinical development. Anti-infective regimens can help.
Sepsis patients in ICU were took blood culture sample and blood sample for mNGS test (IDSeqTM
      Ultra, Combing with Metagenomics and Pathogen/AMR/VF Probe Enrichment). Clinicians use their
      knowledge and experience to decide antibiotics use with the guide of Culture results or mNGS
      results. Validation with digital droplet PCR assays when metagenomic full-targeted assays
      identify pathogens not identified in conventional blood cultures The difference between the
      positive rate of mNGS and the positive rate of blood culture were recorded. Patient were
      followed at least 28 days after enrollment or an outcome indicator. Possible scenarios for
      detecting clinical impact were detected. Etiology, biochemical indicators, immune function,
      infection indicator, secondary infection, SOFA score and length of stay，outcome were
      recorded.
observational model: Cohort
time perspective: Prospective
measure: difference of positive rate between mNGS and Culture
time frame: 28 day
description: The difference between the positive rate of mNGS and the positive rate of blood culture.
measure: The difference between the positive rate of metagenomic full capture technology and the Category of Clinical Impact
time frame: 28 day
description: Positive, Negative，None and Indeterminate
measure: Change of SOFA
time frame: 7 day
description: change of SOFA score (include each organ) at baseline, day 3 and day 7 clinical improvement :Improvement in 2 or more clinical signs and symptoms no requirement for additional antibacterial treatment Clinical failure:Persistence or progression of baseline signs and symptoms
measure: Mortality
time frame: During hospitalization
description: 28 day，ICU and hospital mortality Documented microbiologic eradication:Absence of primary microbe from infection site Presumed microbiologic eradication:Clinical cure without available microbiologic culture data Presumed microbiologic persistence:Clinical failure in the absence of any microbiologic data Documented microbiologic persistence:Continued presence of MRSA based on microbiologic culture Superinfection: Clinical failure and isolation of a pathogen not present at baseline at the original infection site
measure: Length of stay
time frame: During hospitalization
description: ICU and hospital length of stay
measure: Anti-infective treatment adjustment
time frame: 28 day
description: each Anti-infective treatment adjustment
measure: pathogen
time frame: 28 day
description: all the detect pathogens from mNGS and blood culture
measure: secondary infection
time frame: 28 day
description: infection secondary to the primary infection
arm group label: Sepsis
description: All enrolled patients
intervention type: Diagnostic Test
intervention name: blood mNGS (IDSeqTM Ultra); blood Culture
description: take blood samples for mNGS and Culture at the same time in sepsis patients. No intervention on the treatment of the patients.
arm group label: Sepsis
DNA extracted from blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Haibo Qiu, MD
role: Study Director
affiliation: Southeast University, China
last name: ling liu, MD
phone: 13851435472
email: liulingdoctor@126.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Southeast University, China
investigator full name: Ling Liu
investigator title: Director