<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/NCT03771313</url>
  </required_header>
  <id_info>
    <org_study_id>Ceftaroline CF PK/PD_2017-2276</org_study_id>
    <nct_id>NCT03771313</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis</brief_title>
  <official_title>Pharmacokinetic and Pharmacodynamic Analysis of Ceftaroline in Children and Adolescents With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, single center, prospective study of patients with a diagnosis of&#xD;
      cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA),&#xD;
      also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with&#xD;
      intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to&#xD;
      current recommendations based upon its approved usage in pediatric patients for community&#xD;
      acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic&#xD;
      (PD) data using serum concentrations of ceftaroline measured at various time-points following&#xD;
      infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric&#xD;
      CF patients that would be tailored to account for bacterial susceptibility and disease&#xD;
      progression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single center, prospective study of patients with a diagnosis of&#xD;
      cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA),&#xD;
      also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with&#xD;
      intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to&#xD;
      current recommendations based upon its approved usage in pediatric patients for community&#xD;
      acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic&#xD;
      (PD) data using serum concentrations of ceftaroline measured at various time-points following&#xD;
      infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric&#xD;
      CF patients that would be tailored to account for bacterial susceptibility and disease&#xD;
      progression and determine if current dosing regimes used are appropriate for this patient&#xD;
      population.&#xD;
&#xD;
      Blood samples will be collected prior to infusion of ceftaroline and at approximately 1 hour&#xD;
      (+/- 10 minutes), 1.5 hours (+/- 10 minutes), 3 hours (+/- 30 minutes), and 6 hours (+/- 30&#xD;
      minutes) after initiation of infusion. The blood samples (0.5 to 1 ml) will be collected&#xD;
      through intravenous access, venipuncture, or capillary blood puncture. Samples will be&#xD;
      centrifuged at 1500g at 4°C for 15 minutes within 15 minutes of collection. Serum will be&#xD;
      separated into two aliquots of a minimum of 0.2 mL and stored at -70°C until analysis.&#xD;
      Determination of serum ceftaroline concentrations will be measured using high-performance&#xD;
      liquid chromatography (HPLC) method with ultraviolet (UV) detection.&#xD;
&#xD;
      Key clinical data (PK/PD) that will be collected includes age, sex, genotype, growth&#xD;
      parameters, airway microbiology, sweat chloride values, pulmonary function test (FEV1),&#xD;
      concomitant medications, and comorbid disorders (i.e.: CF related diabetes, CF liver disease,&#xD;
      short gut, renal dysfunction, pulmonary hypertension, coagulopathy).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Anticipated">July 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Open-label, single center, prospective study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Ceftaroline Exposure and PK/PD Target Attainment</measure>
    <time_frame>12-hour maximum, single visit</time_frame>
    <description>Interpret PK/PD target attainment based on percent time of the free ceftaroline concentration (=PK) above minimum inhibitory concentration (=PD index)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FEV1 Percentage Change Assessment</measure>
    <time_frame>12-hour maximum, single visit</time_frame>
    <description>Assess change in FEV1 percent predicted during ceftaroline treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Failures</measure>
    <time_frame>12-hour maximum, single visit</time_frame>
    <description>Assess any treatment failures as evidenced by provider documentation (including FEV1 not improving and/or change in antimicrobial drugs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side Effects</measure>
    <time_frame>12-hour maximum, single visit</time_frame>
    <description>Assess for side effects as documented by providers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary Exacerbations</measure>
    <time_frame>12-hour maximum, single visit</time_frame>
    <description>Assess for time until next pulmonary exacerbation</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>PK/PD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Open-label prospective study with participants receiving treating physician-approved intravenous ceftaroline, dosed according to current recommendations. Blood samples collected at baseline, 1 hour, 1.5 hours, 3 hours, and 6 hours after infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceftaroline</intervention_name>
    <description>Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. Blood samples will be collected for PK/PD analysis.</description>
    <arm_group_label>PK/PD</arm_group_label>
    <other_name>Ceftaroline fosamil,Teflaro, Zinforo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cystic Fibrosis diagnosis on accepted Cystic Fibrosis Foundation guidelines&#xD;
&#xD;
          -  Inpatient&#xD;
&#xD;
          -  Decision by treating physician to use intravenous ceftaroline&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  less than 2 years old&#xD;
&#xD;
          -  22 years of age or older&#xD;
&#xD;
          -  less than 15 kg weight&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) &gt; 5 fold upper&#xD;
             limit of normal&#xD;
&#xD;
          -  Gamma-glutamyltransferase (GGT) &gt; 3 fold above upper limit of normal&#xD;
&#xD;
          -  Total bilirubin &gt; 2 mg/dL&#xD;
&#xD;
          -  Platelets &lt; 50,000&#xD;
&#xD;
          -  Patients without documented CF&#xD;
&#xD;
          -  Non-English speaking patients/families&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexander Vinks, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>42229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>August 29, 2022</last_update_submitted>
  <last_update_submitted_qc>August 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2022</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>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ceftaroline fosamil</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03771313
org study id: Ceftaroline CF PK/PD_2017-2276
nct id: NCT03771313
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, single center, prospective study of patients with a diagnosis of
      cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA),
      also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with
      intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to
      current recommendations based upon its approved usage in pediatric patients for community
      acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic
      (PD) data using serum concentrations of ceftaroline measured at various time-points following
      infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric
      CF patients that would be tailored to account for bacterial susceptibility and disease
      progression.
This is an open-label, single center, prospective study of patients with a diagnosis of
      cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus (MRSA),
      also known as oxacillin-resistant Staphylococcus aureus (ORSA), being treated with
      intravenous ceftaroline. Patients will have intravenous ceftaroline dosed according to
      current recommendations based upon its approved usage in pediatric patients for community
      acquired pneumonia. The investigators will analyze pharmacokinetic (PK) and pharmacodynamic
      (PD) data using serum concentrations of ceftaroline measured at various time-points following
      infusion of ceftaroline to develop PK/PD guided dosing strategies of ceftaroline in pediatric
      CF patients that would be tailored to account for bacterial susceptibility and disease
      progression and determine if current dosing regimes used are appropriate for this patient
      population.

      Blood samples will be collected prior to infusion of ceftaroline and at approximately 1 hour
      (+/- 10 minutes), 1.5 hours (+/- 10 minutes), 3 hours (+/- 30 minutes), and 6 hours (+/- 30
      minutes) after initiation of infusion. The blood samples (0.5 to 1 ml) will be collected
      through intravenous access, venipuncture, or capillary blood puncture. Samples will be
      centrifuged at 1500g at 4°C for 15 minutes within 15 minutes of collection. Serum will be
      separated into two aliquots of a minimum of 0.2 mL and stored at -70°C until analysis.
      Determination of serum ceftaroline concentrations will be measured using high-performance
      liquid chromatography (HPLC) method with ultraviolet (UV) detection.

      Key clinical data (PK/PD) that will be collected includes age, sex, genotype, growth
      parameters, airway microbiology, sweat chloride values, pulmonary function test (FEV1),
      concomitant medications, and comorbid disorders (i.e.: CF related diabetes, CF liver disease,
      short gut, renal dysfunction, pulmonary hypertension, coagulopathy).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open-label, single center, prospective study
primary purpose: Treatment
masking: None (Open Label)
masking description: Open label
measure: Ceftaroline Exposure and PK/PD Target Attainment
time frame: 12-hour maximum, single visit
description: Interpret PK/PD target attainment based on percent time of the free ceftaroline concentration (=PK) above minimum inhibitory concentration (=PD index)
measure: FEV1 Percentage Change Assessment
time frame: 12-hour maximum, single visit
description: Assess change in FEV1 percent predicted during ceftaroline treatment
measure: Treatment Failures
time frame: 12-hour maximum, single visit
description: Assess any treatment failures as evidenced by provider documentation (including FEV1 not improving and/or change in antimicrobial drugs)
measure: Side Effects
time frame: 12-hour maximum, single visit
description: Assess for side effects as documented by providers
measure: Pulmonary Exacerbations
time frame: 12-hour maximum, single visit
description: Assess for time until next pulmonary exacerbation
arm group label: PK/PD
arm group type: Other
description: Open-label prospective study with participants receiving treating physician-approved intravenous ceftaroline, dosed according to current recommendations. Blood samples collected at baseline, 1 hour, 1.5 hours, 3 hours, and 6 hours after infusion.
intervention type: Drug
intervention name: Ceftaroline
description: Patients will have intravenous ceftaroline dosed according to current recommendations based upon its approved usage in pediatric patients for community acquired pneumonia. Blood samples will be collected for PK/PD analysis.
arm group label: PK/PD
other name: Ceftaroline fosamil,Teflaro, Zinforo
criteria: 
gender: All
minimum age: 2 Years
maximum age: 21 Years
healthy volunteers: No
last name: Alexander Vinks, PhD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Ceftaroline fosamil