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/NCT06026852</url>
    </required_header>
    <id_info>
      <org_study_id>CIV-23-04-042892</org_study_id>
      <nct_id>NCT06026852</nct_id>
    </id_info>
    <brief_title>Validation of Betalactam ML Prediction Models - TDMAide</brief_title>
    <acronym>TDMAide</acronym>
    <official_title>Validation of Uncertainty Quantifying Machine Learning Models to Predict Beta-lactam Antimicrobial Concentrations in ICU Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Ghent</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Research Foundation Flanders</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Imec</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University Hospital, Ghent</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this study is to learn about the real wold behavior of developed machine learning&#xD;
        models that predict the plasma concentration of piperacillin-tazobactam and meropenem in&#xD;
        critically ill patients admitted to the intensive care unit (ICU).&#xD;
  &#xD;
        The main aim of the study is to validate the performance of these machine learning models. To&#xD;
        this end, daily measured plasma concentrations of the investigated antimicrobials will be&#xD;
        compared with the predicted concentration by the machine learning algorithms.&#xD;
  &#xD;
        Additional goals of the study include:&#xD;
  &#xD;
          -  To describe the total plasma concentration over time of piperacillin-tazobactam and&#xD;
             meropenem in patients admitted to the ICU.&#xD;
  &#xD;
          -  To quantify the correlation between plasma concentrations of piperacillin-tazobactam and&#xD;
             meropenem and the development of side effects.&#xD;
  &#xD;
          -  To evaluate the perceived necessity of therapeutic drug monitoring (TDM) of consultants&#xD;
             and physicians in training working in the ICU.&#xD;
  &#xD;
          -  To evaluate the perceived added value of daily TDM.&#xD;
  &#xD;
        Samples (where possible taken routinely) from participating patients will be analyzed for&#xD;
        meropenem and piperacillin-tazobactam plasma concentration. Participating physicians will be&#xD;
        asked to fill in a short daily questionnaire during the time a patient under their care is&#xD;
        treated with the antimicrobial under investigation.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">May 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Difference between predicted (TDMAIde) and measured (via HPLC-MS/MS method) plasma concentrations</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>The difference between the predicted concentration (from the TDMAide software) and the concentration range based on the measured concentration (measured from the blood sample from the patient and analyzed using a HPLC-MS/MS method, with and without taking into account intra- and inter measurement variabilities of the HPLC-MS/MS method.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration (determined via HPLC-MS/MS) trends</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>Trends in total plasma concentration over time of piperacillin-tazobactam and meropenem in patients admitted to the ICU</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation between plasma concentrations (measured by HPLC-MS/MS) and side effects as percentage of patients experiencing the side effect</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>The correlation between plasma concentrations of piperacillin-tazobactam and meropenem and the development of renal (decline in urinary output, rise in serum creatinin), gastro-intestinal (C. difficile infections, stool consistency, elevation of ALT/AST/gamma GT/Alkalic fosfatase/INR/APTT/bilirubin), neurological (delirium as measured by Intensice Care Delirium Screening Checklist - ICDSC) or hematological (Rise or fall of thrombocytes, development of leucopenia/agranulocytosis/eosinophelia/hemolytic anemia) side effects.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Perceived necessity of therapeutic drug monitoring</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>The perceived necessity of therapeutic drug monitoring of consultants and physicians in training working in the ICU by evaluating the perceived necessity collected during the surveys with the measured plasma concentrations.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Perceived added value of therapeutic drug monitoring</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>The perceived added value of daily therapeutic drug monitoring from the responses to the survey</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">600</enrollment>
    <condition>Infections</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Patients admitted to the ICU who are treated with piperacillin-tazobactam or meropenem.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Physicians</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Physicians in training or consultants who care for patients that are included in the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Prediction of plasma concentration of piperacillin-tazobactam or meropenem</intervention_name>
      <description>For included patients, a prediction will be made by developed machine learning models about the expected plasma concentration of piperacillin-tazobactam or meropenem by using routinely collected health care data.</description>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Determination of plasma concentration of piperacillin-tazobactam or meropenem</intervention_name>
      <description>For included patients, the total plasma concentration of piperacillin-tazobactam or meropenem will be determined. Were possible, this will be done using a blood sample that was collected during routine daily bloodwork which is performed in the morning. If no routine sample is available, a study specific sample will be drawn at approximately the same time as a routine sample would be drawn.</description>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Daily short questionnaire</intervention_name>
      <description>Physicians who care for patients included in the study will be asked to fill in a short daily questionnaire that evaluates the perceived necessity and added value of daily therapeutic drug monitoring.</description>
      <arm_group_label>Physicians</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Patients&#xD;
  &#xD;
          Inclusion Criteria:&#xD;
  &#xD;
            -  Admission to the ICU.&#xD;
  &#xD;
            -  Age above 18 years old.&#xD;
  &#xD;
            -  Treatment with piperacillin-tazobactam or meropenem for less than 48 hours.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant or lactating patients.&#xD;
  &#xD;
            -  Limitation of therapy beyond &quot;Do not resuscitate&quot;.&#xD;
  &#xD;
            -  Expected demise within 48 hours after inclusion.&#xD;
  &#xD;
            -  Haemoglobin &lt; 7 g/dL.&#xD;
  &#xD;
            -  Previous inclusion in this study for a treatment course with the same antimicrobial.&#xD;
  &#xD;
          Consultants and physicians in training&#xD;
  &#xD;
          Inclusion Criteria:&#xD;
  &#xD;
            -  Consultant or physician in training working in the ICU.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  None&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>100 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jan De Waele, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Hospital, Ghent</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Thomas De Corte, MD</last_name>
      <phone>0032093324134</phone>
      <email>thomas.decorte@uzgent.be</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Hospital, Ghent</name>
        <address>
          <city>Ghent</city>
          <zip>9000</zip>
          <country>Belgium</country>
        </address>
      </facility>
      <contact>
        <last_name>Jan De Waele, MD, PhD</last_name>
      </contact>
      <investigator>
        <last_name>Jan De Waele, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Belgium</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Artificial Intelligence</keyword>
    <keyword>Machine Learning</keyword>
    <keyword>PK/PD</keyword>
    <keyword>Piperacillin-tazobactam</keyword>
    <keyword>Meropenem</keyword>
    <keyword>Intensive Care Unit</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Meropenem</mesh_term>
      <mesh_term>Tazobactam</mesh_term>
      <mesh_term>Piperacillin</mesh_term>
      <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Individual participant data will be made available upon reasonable request and after approval by the appropriate ethical and regulatory bodies.</ipd_description>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>At publication of the results</ipd_time_frame>
      <ipd_access_criteria>Individual participant data will be made available upon reasonable request and after approval by the appropriate ethical and regulatory bodies.</ipd_access_criteria>
    </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/NCT06026852
  org study id: CIV-23-04-042892
  nct id: NCT06026852
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The goal of this study is to learn about the real wold behavior of developed machine learning
        models that predict the plasma concentration of piperacillin-tazobactam and meropenem in
        critically ill patients admitted to the intensive care unit (ICU).
  
        The main aim of the study is to validate the performance of these machine learning models. To
        this end, daily measured plasma concentrations of the investigated antimicrobials will be
        compared with the predicted concentration by the machine learning algorithms.
  
        Additional goals of the study include:
  
          -  To describe the total plasma concentration over time of piperacillin-tazobactam and
             meropenem in patients admitted to the ICU.
  
          -  To quantify the correlation between plasma concentrations of piperacillin-tazobactam and
             meropenem and the development of side effects.
  
          -  To evaluate the perceived necessity of therapeutic drug monitoring (TDM) of consultants
             and physicians in training working in the ICU.
  
          -  To evaluate the perceived added value of daily TDM.
  
        Samples (where possible taken routinely) from participating patients will be analyzed for
        meropenem and piperacillin-tazobactam plasma concentration. Participating physicians will be
        asked to fill in a short daily questionnaire during the time a patient under their care is
        treated with the antimicrobial under investigation.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Difference between predicted (TDMAIde) and measured (via HPLC-MS/MS method) plasma concentrations
  time frame: Through study completion, an average of 1 year
  description: The difference between the predicted concentration (from the TDMAide software) and the concentration range based on the measured concentration (measured from the blood sample from the patient and analyzed using a HPLC-MS/MS method, with and without taking into account intra- and inter measurement variabilities of the HPLC-MS/MS method.
  measure: Plasma concentration (determined via HPLC-MS/MS) trends
  time frame: Through study completion, an average of 1 year
  description: Trends in total plasma concentration over time of piperacillin-tazobactam and meropenem in patients admitted to the ICU
  measure: Correlation between plasma concentrations (measured by HPLC-MS/MS) and side effects as percentage of patients experiencing the side effect
  time frame: Through study completion, an average of 1 year
  description: The correlation between plasma concentrations of piperacillin-tazobactam and meropenem and the development of renal (decline in urinary output, rise in serum creatinin), gastro-intestinal (C. difficile infections, stool consistency, elevation of ALT/AST/gamma GT/Alkalic fosfatase/INR/APTT/bilirubin), neurological (delirium as measured by Intensice Care Delirium Screening Checklist - ICDSC) or hematological (Rise or fall of thrombocytes, development of leucopenia/agranulocytosis/eosinophelia/hemolytic anemia) side effects.
  measure: Perceived necessity of therapeutic drug monitoring
  time frame: Through study completion, an average of 1 year
  description: The perceived necessity of therapeutic drug monitoring of consultants and physicians in training working in the ICU by evaluating the perceived necessity collected during the surveys with the measured plasma concentrations.
  measure: Perceived added value of therapeutic drug monitoring
  time frame: Through study completion, an average of 1 year
  description: The perceived added value of daily therapeutic drug monitoring from the responses to the survey
  arm group label: Patients
  arm group type: Other
  description: Patients admitted to the ICU who are treated with piperacillin-tazobactam or meropenem.
  arm group label: Physicians
  arm group type: Other
  description: Physicians in training or consultants who care for patients that are included in the study.
  intervention type: Device
  intervention name: Prediction of plasma concentration of piperacillin-tazobactam or meropenem
  description: For included patients, a prediction will be made by developed machine learning models about the expected plasma concentration of piperacillin-tazobactam or meropenem by using routinely collected health care data.
  arm group label: Patients
  intervention type: Diagnostic Test
  intervention name: Determination of plasma concentration of piperacillin-tazobactam or meropenem
  description: For included patients, the total plasma concentration of piperacillin-tazobactam or meropenem will be determined. Were possible, this will be done using a blood sample that was collected during routine daily bloodwork which is performed in the morning. If no routine sample is available, a study specific sample will be drawn at approximately the same time as a routine sample would be drawn.
  arm group label: Patients
  intervention type: Other
  intervention name: Daily short questionnaire
  description: Physicians who care for patients included in the study will be asked to fill in a short daily questionnaire that evaluates the perceived necessity and added value of daily therapeutic drug monitoring.
  arm group label: Physicians
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 100 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Jan De Waele, MD, PhD
  role: Principal Investigator
  affiliation: University Hospital, Ghent
  last name: Thomas De Corte, MD
  phone: 0032093324134
  email: thomas.decorte@uzgent.be
  facility: 
  contact: 
  investigator: 
  country: Belgium
  responsible party type: Sponsor
  mesh term: Meropenem
  mesh term: Tazobactam
  mesh term: Piperacillin
  mesh term: Piperacillin, Tazobactam Drug Combination
  sharing ipd: Yes
  ipd description: Individual participant data will be made available upon reasonable request and after approval by the appropriate ethical and regulatory bodies.
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: At publication of the results
  ipd access criteria: Individual participant data will be made available upon reasonable request and after approval by the appropriate ethical and regulatory bodies.