<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/NCT02998411</url>
  </required_header>
  <id_info>
    <org_study_id>NI16012</org_study_id>
    <nct_id>NCT02998411</nct_id>
  </id_info>
  <brief_title>Population Pharmacokinetics of Anti-infectives in Hospitalized Patients</brief_title>
  <acronym>OptiPOP</acronym>
  <official_title>Population Pharmacokinetics Approaches for the Optimization of Anti-infective Concentrations Among Hospitalized Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In case of sepsis, the therapeutic success is strongly influenced by the choice of&#xD;
      anti-infectives (AI) in terms of spectrum, dosage and administration schedule. It is&#xD;
      therefore critical to achieve adequate AI concentration as quickly as possible.&#xD;
&#xD;
      This protocol aims to define a common framework to studies conducted jointly by the&#xD;
      Antimicrobial Stewardship Tea, the Pharmacology department of Cochin hospital and within the&#xD;
      APHP Centre hospital group for various AI in a range of specific study populations (intensive&#xD;
      care unit patients, neutropenic patients…).&#xD;
&#xD;
      These studies will use mathematical modeling methodologies to investigate the&#xD;
      pharmacokinetics (PK) and pharmacodynamics (PD) of different AI including PK/PD targets or&#xD;
      any other biological compartment. The effects of covariates on PK and PD parameters will be&#xD;
      investigated to better explain the between-subject variability (BSV) and to ultimately&#xD;
      suggest individualized dosage regimens.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with sepsis who receive inadequate AI regimen have a high risk of poor clinical&#xD;
      outcomes. It is therefore critical to achieve adequate concentration of the AI as quickly as&#xD;
      possible in these patients.&#xD;
&#xD;
      Pharmacokinetics (PK) describes the drug concentration-time courses in body fluids resulting&#xD;
      from administration of a certain drug dose, pharmacodynamics (PD) the observed effect&#xD;
      resulting from a certain drug concentration. The three PK/PD indices most commonly evaluated&#xD;
      for AI are: the ratio of the maximal unbound drug concentration to the MIC (fCmax/MIC), the&#xD;
      ratio of the area under the unbound drug concentration-time curve to the MIC (fAUC/MIC) or&#xD;
      the percentage of a 24 h time period where the unbound drug concentration exceeds the MIC&#xD;
      (fT.MIC). Dosing regimens are chosen to reach a target value of the main PK/PD index.&#xD;
&#xD;
      In hospitalized patients, a high between-subject variability is expected on PK parameters,&#xD;
      related to the severity of the disease (sepsis, neutropenia, organ failure...), weight, age&#xD;
      (geriatric patients, neonates...) and the co-administration of other medications leading to&#xD;
      potential drug interactions. The PD variability is strongly influenced by the immune status,&#xD;
      type of infection, inoculum size, comorbidities.&#xD;
&#xD;
      The optiPOP protocol aims to define a common framework to PK/PD studies conducted jointly by&#xD;
      the Antimicrobial Stewardship Team, the Pharmacology department of Cochin hospital and within&#xD;
      the APHP Centre hospital group.&#xD;
&#xD;
      These studies will use mathematical population pharmacokinetic modeling methodologies to&#xD;
      investigate PK/PD parameters of various AI in a range of specific study populations (ICU,&#xD;
      neutropenic patients…). The effects of covariates on PK and PD parameters will be&#xD;
      investigated in order to better explain the between-subject variability and to ultimately&#xD;
      suggest individualized dosage regimens.&#xD;
&#xD;
      OptiPOP is a prospective, non-interventional, single center study, based on data regularly&#xD;
      collected during the therapeutic drug monitoring of AI.&#xD;
&#xD;
      The antimicrobial stewardship team (AST) has a role in advising clinicians for the diagnostic&#xD;
      and treatment of infectious diseases. It is closely involved in daily therapeutic drug&#xD;
      monitoring of AI, in collaboration with the department of pharmacology and within the APHP&#xD;
      Centre hospital group. Patient selection will take place in all medical and surgical wards of&#xD;
      the hospital. The AST senior physician will check the eligibility criteria and propose the&#xD;
      study to the patient, in accordance with the referring physician. Any adult patient requiring&#xD;
      the administration of an AI with at least one plasma concentration measurement or any other&#xD;
      biological compartment conducted in Cochin department of pharmacology and within the APHP&#xD;
      Centre hospital group will be eligible. The AST physician will give a briefing note to the&#xD;
      patient, and the non-oral opposition for the retrieval and analysis of data will be&#xD;
      collected.&#xD;
&#xD;
      No intervention or no charge will be made for this study. It is planned to include 60&#xD;
      patients per molecule.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Anti-infectives concentration</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite measure of the health condition</measure>
    <time_frame>28 days</time_frame>
    <description>Clinical and laboratory data : anthropometric characteristics; organs function, severity score, type of infection, micro-organsim and sensitivity, infectious biological parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Inhibitory Concentration (MIC) of the suspected or documented pathogen</measure>
    <time_frame>28 days</time_frame>
    <description>Pharmacodynamic characteristics of the molecule</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Patient Receiving Anti-infectives Whatever Disease</condition>
  <arm_group>
    <arm_group_label>AI treatment and dosage</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Titration</intervention_name>
    <arm_group_label>AI treatment and dosage</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adults patients hospitalized in Cochin hospital receiving an AI agent and who require at&#xD;
        least one AI concentration measurement or any other biological compartment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Every adult hospitalized in Cochin hospital, receiving an AI and who require at least&#xD;
             one AI concentration measurement or any other biological compartment in the Cochin&#xD;
             department of pharmacology&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient having notified to the physician the refusal for data recovery&#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>Solen KERNEIS, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Solen KERNEIS, MD, PhD</last_name>
    <phone>01 40 25 84 20</phone>
    <email>solen.kerneis@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laure CHOUPEAUX, Master</last_name>
    <phone>01 44 38 17 11</phone>
    <email>elodie.henry@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Bichat (AP-HP)</name>
      <address>
        <city>Paris</city>
        <zip>75018</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Solen KERNEIS, MD, PhD</last_name>
      <phone>01 40 25 61 99</phone>
      <email>solen.kerneis@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anti-infectives</keyword>
  <keyword>adults</keyword>
  <keyword>pharmacokinetic</keyword>
  <keyword>pharmacodynamic end-points</keyword>
  <keyword>clinical cure</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02998411
org study id: NI16012
nct id: NCT02998411
lead sponsor: 
has dmc: No
In case of sepsis, the therapeutic success is strongly influenced by the choice of
      anti-infectives (AI) in terms of spectrum, dosage and administration schedule. It is
      therefore critical to achieve adequate AI concentration as quickly as possible.

      This protocol aims to define a common framework to studies conducted jointly by the
      Antimicrobial Stewardship Tea, the Pharmacology department of Cochin hospital and within the
      APHP Centre hospital group for various AI in a range of specific study populations (intensive
      care unit patients, neutropenic patients…).

      These studies will use mathematical modeling methodologies to investigate the
      pharmacokinetics (PK) and pharmacodynamics (PD) of different AI including PK/PD targets or
      any other biological compartment. The effects of covariates on PK and PD parameters will be
      investigated to better explain the between-subject variability (BSV) and to ultimately
      suggest individualized dosage regimens.
Patients with sepsis who receive inadequate AI regimen have a high risk of poor clinical
      outcomes. It is therefore critical to achieve adequate concentration of the AI as quickly as
      possible in these patients.

      Pharmacokinetics (PK) describes the drug concentration-time courses in body fluids resulting
      from administration of a certain drug dose, pharmacodynamics (PD) the observed effect
      resulting from a certain drug concentration. The three PK/PD indices most commonly evaluated
      for AI are: the ratio of the maximal unbound drug concentration to the MIC (fCmax/MIC), the
      ratio of the area under the unbound drug concentration-time curve to the MIC (fAUC/MIC) or
      the percentage of a 24 h time period where the unbound drug concentration exceeds the MIC
      (fT.MIC). Dosing regimens are chosen to reach a target value of the main PK/PD index.

      In hospitalized patients, a high between-subject variability is expected on PK parameters,
      related to the severity of the disease (sepsis, neutropenia, organ failure...), weight, age
      (geriatric patients, neonates...) and the co-administration of other medications leading to
      potential drug interactions. The PD variability is strongly influenced by the immune status,
      type of infection, inoculum size, comorbidities.

      The optiPOP protocol aims to define a common framework to PK/PD studies conducted jointly by
      the Antimicrobial Stewardship Team, the Pharmacology department of Cochin hospital and within
      the APHP Centre hospital group.

      These studies will use mathematical population pharmacokinetic modeling methodologies to
      investigate PK/PD parameters of various AI in a range of specific study populations (ICU,
      neutropenic patients…). The effects of covariates on PK and PD parameters will be
      investigated in order to better explain the between-subject variability and to ultimately
      suggest individualized dosage regimens.

      OptiPOP is a prospective, non-interventional, single center study, based on data regularly
      collected during the therapeutic drug monitoring of AI.

      The antimicrobial stewardship team (AST) has a role in advising clinicians for the diagnostic
      and treatment of infectious diseases. It is closely involved in daily therapeutic drug
      monitoring of AI, in collaboration with the department of pharmacology and within the APHP
      Centre hospital group. Patient selection will take place in all medical and surgical wards of
      the hospital. The AST senior physician will check the eligibility criteria and propose the
      study to the patient, in accordance with the referring physician. Any adult patient requiring
      the administration of an AI with at least one plasma concentration measurement or any other
      biological compartment conducted in Cochin department of pharmacology and within the APHP
      Centre hospital group will be eligible. The AST physician will give a briefing note to the
      patient, and the non-oral opposition for the retrieval and analysis of data will be
      collected.

      No intervention or no charge will be made for this study. It is planned to include 60
      patients per molecule.
observational model: Cohort
time perspective: Prospective
measure: Anti-infectives concentration
time frame: 28 days
measure: Composite measure of the health condition
time frame: 28 days
description: Clinical and laboratory data : anthropometric characteristics; organs function, severity score, type of infection, micro-organsim and sensitivity, infectious biological parameters
measure: Minimum Inhibitory Concentration (MIC) of the suspected or documented pathogen
time frame: 28 days
description: Pharmacodynamic characteristics of the molecule
arm group label: AI treatment and dosage
intervention type: Other
intervention name: Titration
arm group label: AI treatment and dosage
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Solen KERNEIS, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Solen KERNEIS, MD, PhD
phone: 01 40 25 84 20
email: solen.kerneis@aphp.fr
last name: Laure CHOUPEAUX, Master
phone: 01 44 38 17 11
email: elodie.henry@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
sharing ipd: No