<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/NCT04493151</url>
  </required_header>
  <id_info>
    <org_study_id>59752</org_study_id>
    <nct_id>NCT04493151</nct_id>
  </id_info>
  <brief_title>Imipenem/Cilastatin/Relebactam PK in ECMO</brief_title>
  <official_title>Pharmacokinetics of Imipenem/Cilastatin/Relebactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joseph L. Kuti, PharmD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hartford Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      Extracorporeal membrane oxygenation (ECMO) is a from of cardiopulmonary life-support for&#xD;
      critically ill patients where blood is extracted from the vascular system and circulated by a&#xD;
      mechanical pump while it is oxygenated and re-infused into the patient's circulation. It is&#xD;
      well known that critically ill patients may experience alterations in antibiotic&#xD;
      pharmacokinetics, and as a result, dosing modifications are generally required. There is a&#xD;
      need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs.&#xD;
      This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic,&#xD;
      imipenem-cilastatin-relebactam, in critically ill patients receiving ECMO.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single center, open-label study to determine imipenem-cilastatin-relebactam&#xD;
      pharmacokinetics in critically ill patients receiving ECMO. Eight patients with suspected&#xD;
      suspected sepsis and who are receiving ECMO will be enrolled. Each participant will receive&#xD;
      four to six doses of imipenem-cilastatin-relebactam according to current approved prescribing&#xD;
      information, followed by ten blood samples to determine concentrations. Non-compartmental and&#xD;
      population pharmacokinetic analyses will be determined to assess the effects of ECMO on&#xD;
      imipenem and relebactam pharmacokinetic parameters.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2021</start_date>
  <completion_date type="Anticipated">November 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Imipenem Clearance</measure>
    <time_frame>6 hours</time_frame>
    <description>The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relebactam Clearance</measure>
    <time_frame>6 hours</time_frame>
    <description>The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Imipenem Area Under the Curve (AUC)</measure>
    <time_frame>6 hours</time_frame>
    <description>The AUC in milligram*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relebactam Area Under the Curve (AUC)</measure>
    <time_frame>6 hours</time_frame>
    <description>The AUC in milligram*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">8</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Imipenem-Cilastatin-Relebactam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Imipenem, Cilastatin and Relebactam</intervention_name>
    <description>After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.</description>
    <arm_group_label>Imipenem-Cilastatin-Relebactam</arm_group_label>
    <other_name>Recarbrio</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older;&#xD;
&#xD;
          -  On support with Veno-venous- or Veno-arterial-ECMO;&#xD;
&#xD;
          -  Documented infection or presumed infection as confirmed by the presence of at least&#xD;
             one of the following criteria within the past 72 hours:&#xD;
&#xD;
               -  Documented fever (oral, rectal, tympanic, or core temperature &gt; 38.5° C)&#xD;
&#xD;
               -  Hypothermia (oral, rectal, tympanic, or core temperature &lt; 35.0° C)&#xD;
&#xD;
               -  An elevated white blood cell (WBC) count ≥ 12,000 cells/mm3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  If female, currently pregnant or breast feeding;&#xD;
&#xD;
          -  History of any moderate or severe hypersensitivity or allergic reaction to any&#xD;
             β-lactam agent (a history of mild rash to a β-lactam followed by uneventful&#xD;
             re-exposure is not a contraindication);&#xD;
&#xD;
          -  Severe renal dysfunction defined as a creatinine clearance &lt; 15 mL/min (calculated by&#xD;
             the Cockcroft-Gault equation using actual body weight) or requirement for continuous&#xD;
             renal replacement therapy or hemodialysis;&#xD;
&#xD;
          -  Hemoglobin less than 8 mg/dL at baseline;&#xD;
&#xD;
          -  Use of probenecid, valproic acid, or imipenem within 3 days before study drug&#xD;
             infusion;&#xD;
&#xD;
          -  Acute liver injury, defined as aspartate aminotransferase (AST) or alanine&#xD;
             aminotransferase (ALT) &gt; 5 times the upper limit of normal, or AST or ALT &gt; 3 times&#xD;
             the upper limit of normal with an associated total bilirubin &gt; 2 times upper limit of&#xD;
             normal;&#xD;
&#xD;
          -  Any rapidly-progressing disease or immediately life-threatening illness (defined as&#xD;
             imminent death within 48 hours in the opinion of the investigator);&#xD;
&#xD;
          -  Any condition or circumstance that, in the opinion of the investigator, would&#xD;
             compromise the safety of the patient or the quality of study data;&#xD;
&#xD;
          -  Planned or prior participation in any other interventional drug study within 30 days.&#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>Joseph L Kuti, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hartford Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joseph L Kuti, PharmD</last_name>
    <phone>8609723612</phone>
    <email>joseph.kuti@hhchealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elizabeth Cyr</last_name>
    <phone>8609729290</phone>
    <email>elizabeth.cyr@hhchealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph L Kuti, PharmD</last_name>
      <phone>860-972-3612</phone>
      <email>joseph.kuti@hhchealth.org</email>
    </contact>
    <investigator>
      <last_name>David P Nicolau, PharmD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tomefa Asempa, PharmD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jason Gluck, DO</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hartford Hospital</investigator_affiliation>
    <investigator_full_name>Joseph L. Kuti, PharmD</investigator_full_name>
    <investigator_title>Associate Director, Center for Anti-Infective Research and Development</investigator_title>
  </responsible_party>
  <keyword>beta-lactam</keyword>
  <keyword>pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imipenem</mesh_term>
    <mesh_term>Relebactam</mesh_term>
    <mesh_term>Cilastatin</mesh_term>
  </intervention_browse>
  <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/NCT04493151
org study id: 59752
nct id: NCT04493151
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Extracorporeal membrane oxygenation (ECMO) is a from of cardiopulmonary life-support for
      critically ill patients where blood is extracted from the vascular system and circulated by a
      mechanical pump while it is oxygenated and re-infused into the patient's circulation. It is
      well known that critically ill patients may experience alterations in antibiotic
      pharmacokinetics, and as a result, dosing modifications are generally required. There is a
      need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs.
      This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic,
      imipenem-cilastatin-relebactam, in critically ill patients receiving ECMO.
This is a single center, open-label study to determine imipenem-cilastatin-relebactam
      pharmacokinetics in critically ill patients receiving ECMO. Eight patients with suspected
      suspected sepsis and who are receiving ECMO will be enrolled. Each participant will receive
      four to six doses of imipenem-cilastatin-relebactam according to current approved prescribing
      information, followed by ten blood samples to determine concentrations. Non-compartmental and
      population pharmacokinetic analyses will be determined to assess the effects of ECMO on
      imipenem and relebactam pharmacokinetic parameters.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Imipenem Clearance
time frame: 6 hours
description: The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.
measure: Relebactam Clearance
time frame: 6 hours
description: The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.
measure: Imipenem Area Under the Curve (AUC)
time frame: 6 hours
description: The AUC in milligram*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state
measure: Relebactam Area Under the Curve (AUC)
time frame: 6 hours
description: The AUC in milligram*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state
arm group label: Imipenem-Cilastatin-Relebactam
arm group type: Experimental
description: Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
intervention type: Drug
intervention name: Imipenem, Cilastatin and Relebactam
description: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
arm group label: Imipenem-Cilastatin-Relebactam
other name: Recarbrio
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph L Kuti, PharmD
role: Principal Investigator
affiliation: Hartford Hospital
last name: Joseph L Kuti, PharmD
phone: 8609723612
email: joseph.kuti@hhchealth.org
last name: Elizabeth Cyr
phone: 8609729290
email: elizabeth.cyr@hhchealth.org
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Hartford Hospital
investigator full name: Joseph L. Kuti, PharmD
investigator title: Associate Director, Center for Anti-Infective Research and Development
mesh term: Imipenem
mesh term: Relebactam
mesh term: Cilastatin
sharing ipd: No