xml: <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/NCT05999331</url>
    </required_header>
    <id_info>
      <org_study_id>2023-06-03</org_study_id>
      <nct_id>NCT05999331</nct_id>
    </id_info>
    <brief_title>Elevated Initial APRI Value Was Associated With SALD</brief_title>
    <official_title>Elevated Initial APRI Value Was Associated With the Development of Sepsis-associated Liver Dysfunction in Adult Patients With Sepsis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chinese Medical Association</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Chinese Medical Association</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>
        Sepsis, characterized by severe organ dysfunction related to a dysregulated immune response&#xD;
        to infection, is often life-threatening in clinical settings. Sepsis can progress to multiple&#xD;
        organ dysfunction syndrome (MODS), causing a great risk of mortality. As a vital immune and&#xD;
        metabolic organ, liver often suffers damage in this process and often associated with severe&#xD;
        adverse consequences. Compared to general sepsis population, sepsis-associated liver&#xD;
        dysfunction (SALD) has a higher mortality, up to 68.6%.&#xD;
  &#xD;
        The aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), which can be&#xD;
        calculated from conventional laboratory indicators, has long been used in the evaluation of&#xD;
        liver damage and fibrosis in patients with hepatitis and nonalcoholic fatty liver disease.&#xD;
        AST is a sensitive indicator of early liver function impairment. Additionally, PLT also plays&#xD;
        a crucial role in sepsis-induced MODS through regulating inflammation, maintaining tissue&#xD;
        integrity, and defending against infection. Study found that APRI was a good predictor of&#xD;
        SALD occurrence in pediatric patients with sepsis. Furthermore, APRI has also been used to&#xD;
        predict the prognostic in septic patients with no history of chronic liver disease.&#xD;
  &#xD;
        We conducted a retrospective study based on data from the Medical Information Mart for&#xD;
        Intensive Care IV version 2.2 (MIMIC-IV, v2.2) and our own hospital to explore the potential&#xD;
        association of APRI with the occurrence of SALD in adult patients with sepsis. Furthermore,&#xD;
        we also evaluated the performance of APRI in hypoxic hepatitis and sepsis induced cholestasis&#xD;
        (SIC), which are two subtypes of SALD.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        We included adult sepsis patients (≥18 years) as study participants, but only those who had&#xD;
        data available for their first hospitalization and first ICU admission were enrolled in our&#xD;
        study, if they had multiple admission records in the database. Exclusion criteria include: 1)&#xD;
        all types of chronic liver disease; 2) viral hepatitis; 3) primary acute cholangiopathies; 4)&#xD;
        cholecystitis; 5) hepatic infarction; 6) liver necrosis; 7) liver trauma; 8) length of ICU&#xD;
        stay &lt; 24 hours. Patients without simultaneous AST and PLT data in the first 24 hours after&#xD;
        ICU admission were also excluded.&#xD;
  &#xD;
        The following indicators were extracted directly or derived from the database(MIMIC IV): age;&#xD;
        weight; gender; comorbidity, including hypertension, old myocardial infarct, chronic heart&#xD;
        failure, cerebrovascular disease, chronic pulmonary disease, chronic renal disease and&#xD;
        diabetes; infection site, including blood, lung, skin and soft tissue, abdominal cavity and&#xD;
        urinary tract; disease severity scores within the first day of ICU admission, including Acute&#xD;
        Physiology Score III (APS III), Sequential Organ Failure Assessment (SOFA), Logistic Organ&#xD;
        Dysfunction Score (LODS), Oxford Acute Severity of illness Score (OASIS) and Simplified Acute&#xD;
        Physiology Score II (SAPS II); mean vital signs in first 24h, including heart rate (HR),&#xD;
        systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP),&#xD;
        respiratory rate (RR), temperature and pulse oxygen saturation (SPO2); treatment received&#xD;
        within the first day of ICU admission, including invasive ventilation, vasopressor therapy,&#xD;
        renal replacement therapy and parenteral nutrition (PN) support; initial laboratory&#xD;
        parameters, including white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular&#xD;
        hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume&#xD;
        (MCV), red blood cell (RBC), red blood cell distribution width (RDW), platelet, alanine&#xD;
        aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline&#xD;
        phosphatase (ALP), albumin, blood urea nitrogen (BUN), creatinine, bicarbonate, anionic gap,&#xD;
        sodium, potassium, chloride, total calcium, glucose, prothrombin time (PT), partial&#xD;
        prothrombine time (APTT), international normalized ratio (INR) and APRI; clinical outcome&#xD;
        measures, including intensive care unit (ICU) length of stay (LOS), hospital LOS, ICU&#xD;
        mortality, in-hospital mortality, and 30-day mortality.&#xD;
  &#xD;
        The disease severity scores, including APS III, SOFA, LODS, OASIS, SAPS II, are calculated&#xD;
        using the SQL code provided by Johnson et al. APRI is calculated by (AST(IU/L)/ upper limits&#xD;
        of normal)/PLT(k/uL)×100. Sepsis is diagnosed according to the Third International Consensus&#xD;
        Definitions for Sepsis and Septic Shock (Sepsis-3). Briefly, patients with confirmed or&#xD;
        suspected foci of infectious and a concurrent SOFA≥2. SALD was diagnosed by the following&#xD;
        criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is&#xD;
        further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the&#xD;
        presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated&#xD;
        transaminase (&gt;800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0&#xD;
        mg/dL). Following the exclusion of ineligible patients, the data underwent a thorough&#xD;
        examination, and extreme and erroneous values that failed logical checks were removed.&#xD;
        Variables with missing data exceeding 30% of the sample size were excluded. For the remaining&#xD;
        variables with missing values, the mean imputation method was applied to address them.&#xD;
  &#xD;
        We first used the MIMIC IV database to assess the correlation between APRI and the occurrence&#xD;
        of SALD using association analysis. We then validated these results using our own data.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">January 1, 2019</start_date>
    <completion_date type="Anticipated">September 30, 2023</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
    <study_type>Observational [Patient Registry]</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>
    <target_duration>30 Days</target_duration>
    <primary_outcome>
      <measure>Occurrence of SALD</measure>
      <time_frame>30 days after ICU admission</time_frame>
      <description>Whether SALD occurs</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>mortality</measure>
      <time_frame>30 days after ICU admission</time_frame>
      <description>Death at 30 days after ICU</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">160</enrollment>
    <condition>Liver Dysfunction</condition>
    <condition>Sepsis-associated Liver Dysfunction</condition>
    <arm_group>
      <arm_group_label>Non-SALD group</arm_group_label>
      <description>SALD did not occur in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>SALD group</arm_group_label>
      <description>SALD was occured in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (&gt;800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL).</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>initial aspartate aminotransferase (AST) to platelet (PLT) ratio index</intervention_name>
      <description>All eligible patients were given antibiotics therapy, actively control infection source, as well as other supportive therapy to maintain organ function.</description>
      <arm_group_label>Non-SALD group</arm_group_label>
      <arm_group_label>SALD group</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Briefly, patients with confirmed or suspected foci of infectious and a concurrent SOFA≥2&#xD;
          were diagnosed with sepsis. SALD was diagnosed by the following criteria: (1) ALT or AST≥20&#xD;
          folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  adult sepsis patients (≥18 years)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  all types of chronic liver disease;&#xD;
  &#xD;
            -  viral hepatitis;&#xD;
  &#xD;
            -  primary acute cholangiopathies;&#xD;
  &#xD;
            -  cholecystitis;&#xD;
  &#xD;
            -  hepatic infarction;&#xD;
  &#xD;
            -  liver necrosis;&#xD;
  &#xD;
            -  liver trauma;&#xD;
  &#xD;
            -  length of ICU stay &lt; 24 hours;&#xD;
  &#xD;
            -  Patients without simultaneous AST and PLT data in the first 24 hours after ICU&#xD;
               admission.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Wenkui Yu, professor</last_name>
      <role>Study Chair</role>
      <affiliation>The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Beiyuan Zhang, M.S.</last_name>
      <phone>15005170137</phone>
      <email>1083537599@qq.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Institute of General Surgery of Jinling Hospital</name>
        <address>
          <city>Nanjing</city>
          <state>Jiangsu</state>
          <zip>210002</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Wenkui Yu, Ph.D.</last_name>
        <phone>13701582986</phone>
        <email>yudrnj@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>Dou J, Zhou Y, Cui Y, Chen M, Wang C, Zhang Y. AST-to-Platelet Ratio Index as Potential Early-Warning Biomarker for Sepsis-Associated Liver Injury in Children: A Database Study. Front Pediatr. 2019 Aug 21;7:331. doi: 10.3389/fped.2019.00331. eCollection 2019.</citation>
      <PMID>31497584</PMID>
    </reference>
    <reference>
      <citation>Zhu X, Hu X, Qin X, Pan J, Zhou W. An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study. Pol Arch Intern Med. 2020 Dec 22;130(12):1064-1073. doi: 10.20452/pamw.15699. Epub 2020 Dec 4.</citation>
      <PMID>33274619</PMID>
    </reference>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</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>Liver Diseases</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>N-Methylaspartate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>The research is not over yet</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05999331
  org study id: 2023-06-03
  nct id: NCT05999331
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Sepsis, characterized by severe organ dysfunction related to a dysregulated immune response
        to infection, is often life-threatening in clinical settings. Sepsis can progress to multiple
        organ dysfunction syndrome (MODS), causing a great risk of mortality. As a vital immune and
        metabolic organ, liver often suffers damage in this process and often associated with severe
        adverse consequences. Compared to general sepsis population, sepsis-associated liver
        dysfunction (SALD) has a higher mortality, up to 68.6%.
  
        The aspartate aminotransferase (AST) to platelet (PLT) ratio index (APRI), which can be
        calculated from conventional laboratory indicators, has long been used in the evaluation of
        liver damage and fibrosis in patients with hepatitis and nonalcoholic fatty liver disease.
        AST is a sensitive indicator of early liver function impairment. Additionally, PLT also plays
        a crucial role in sepsis-induced MODS through regulating inflammation, maintaining tissue
        integrity, and defending against infection. Study found that APRI was a good predictor of
        SALD occurrence in pediatric patients with sepsis. Furthermore, APRI has also been used to
        predict the prognostic in septic patients with no history of chronic liver disease.
  
        We conducted a retrospective study based on data from the Medical Information Mart for
        Intensive Care IV version 2.2 (MIMIC-IV, v2.2) and our own hospital to explore the potential
        association of APRI with the occurrence of SALD in adult patients with sepsis. Furthermore,
        we also evaluated the performance of APRI in hypoxic hepatitis and sepsis induced cholestasis
        (SIC), which are two subtypes of SALD.
  We included adult sepsis patients (≥18 years) as study participants, but only those who had
        data available for their first hospitalization and first ICU admission were enrolled in our
        study, if they had multiple admission records in the database. Exclusion criteria include: 1)
        all types of chronic liver disease; 2) viral hepatitis; 3) primary acute cholangiopathies; 4)
        cholecystitis; 5) hepatic infarction; 6) liver necrosis; 7) liver trauma; 8) length of ICU
        stay < 24 hours. Patients without simultaneous AST and PLT data in the first 24 hours after
        ICU admission were also excluded.
  
        The following indicators were extracted directly or derived from the database(MIMIC IV): age;
        weight; gender; comorbidity, including hypertension, old myocardial infarct, chronic heart
        failure, cerebrovascular disease, chronic pulmonary disease, chronic renal disease and
        diabetes; infection site, including blood, lung, skin and soft tissue, abdominal cavity and
        urinary tract; disease severity scores within the first day of ICU admission, including Acute
        Physiology Score III (APS III), Sequential Organ Failure Assessment (SOFA), Logistic Organ
        Dysfunction Score (LODS), Oxford Acute Severity of illness Score (OASIS) and Simplified Acute
        Physiology Score II (SAPS II); mean vital signs in first 24h, including heart rate (HR),
        systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP),
        respiratory rate (RR), temperature and pulse oxygen saturation (SPO2); treatment received
        within the first day of ICU admission, including invasive ventilation, vasopressor therapy,
        renal replacement therapy and parenteral nutrition (PN) support; initial laboratory
        parameters, including white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular
        hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume
        (MCV), red blood cell (RBC), red blood cell distribution width (RDW), platelet, alanine
        aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline
        phosphatase (ALP), albumin, blood urea nitrogen (BUN), creatinine, bicarbonate, anionic gap,
        sodium, potassium, chloride, total calcium, glucose, prothrombin time (PT), partial
        prothrombine time (APTT), international normalized ratio (INR) and APRI; clinical outcome
        measures, including intensive care unit (ICU) length of stay (LOS), hospital LOS, ICU
        mortality, in-hospital mortality, and 30-day mortality.
  
        The disease severity scores, including APS III, SOFA, LODS, OASIS, SAPS II, are calculated
        using the SQL code provided by Johnson et al. APRI is calculated by (AST(IU/L)/ upper limits
        of normal)/PLT(k/uL)×100. Sepsis is diagnosed according to the Third International Consensus
        Definitions for Sepsis and Septic Shock (Sepsis-3). Briefly, patients with confirmed or
        suspected foci of infectious and a concurrent SOFA≥2. SALD was diagnosed by the following
        criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is
        further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the
        presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated
        transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0
        mg/dL). Following the exclusion of ineligible patients, the data underwent a thorough
        examination, and extreme and erroneous values that failed logical checks were removed.
        Variables with missing data exceeding 30% of the sample size were excluded. For the remaining
        variables with missing values, the mean imputation method was applied to address them.
  
        We first used the MIMIC IV database to assess the correlation between APRI and the occurrence
        of SALD using association analysis. We then validated these results using our own data.
  observational model: Cohort
  time perspective: Prospective
  measure: Occurrence of SALD
  time frame: 30 days after ICU admission
  description: Whether SALD occurs
  measure: mortality
  time frame: 30 days after ICU admission
  description: Death at 30 days after ICU
  arm group label: Non-SALD group
  description: SALD did not occur in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL.
  arm group label: SALD group
  description: SALD was occured in adult patients with sepsis during ICU stay.SALD was diagnosed by the following criteria: (1) ALT or AST≥20 folds upper limit of normal level; or (2) TBIL≥2.0 mg/dL. SALD is further divided into hypoxic hepatitis and sepsis induced cholestasis (SIC), based on the presence or absence of elevated TBIL. Hypoxic hepatitis is diagnosed when elevated transaminase (>800 IU/L) is present only; and SIC is diagnosed when TBIL is elevated (≥2.0 mg/dL).
  intervention type: Other
  intervention name: initial aspartate aminotransferase (AST) to platelet (PLT) ratio index
  description: All eligible patients were given antibiotics therapy, actively control infection source, as well as other supportive therapy to maintain organ function.
  arm group label: Non-SALD group
  arm group label: SALD group
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 90 Years
  last name: Wenkui Yu, professor
  role: Study Chair
  affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
  last name: Beiyuan Zhang, M.S.
  phone: 15005170137
  email: 1083537599@qq.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: Dou J, Zhou Y, Cui Y, Chen M, Wang C, Zhang Y. AST-to-Platelet Ratio Index as Potential Early-Warning Biomarker for Sepsis-Associated Liver Injury in Children: A Database Study. Front Pediatr. 2019 Aug 21;7:331. doi: 10.3389/fped.2019.00331. eCollection 2019.
  PMID: 31497584
  citation: Zhu X, Hu X, Qin X, Pan J, Zhou W. An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study. Pol Arch Intern Med. 2020 Dec 22;130(12):1064-1073. doi: 10.20452/pamw.15699. Epub 2020 Dec 4.
  PMID: 33274619
  responsible party type: Sponsor
  mesh term: Sepsis
  mesh term: Liver Diseases
  mesh term: N-Methylaspartate
  sharing ipd: No
  ipd description: The research is not over yet