<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/NCT03246360</url>
  </required_header>
  <id_info>
    <org_study_id>16-PP-04</org_study_id>
    <nct_id>NCT03246360</nct_id>
  </id_info>
  <brief_title>Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin</brief_title>
  <acronym>CLOXA Continue</acronym>
  <official_title>Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin During Bone and Joint Infections: a Prospective, Randomized, Open-label, Monocentric Crossover Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Nice</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Nice</source>
  <oversight_info>
    <has_dmc>No</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>
      Our objective is to establish pharmacological equivalence of intermittent and continuous&#xD;
      infusion of cloxacillin during methicillin-susceptible Staphylococcus aureus (MSSA) bone and&#xD;
      joint infections (BJI). Twelve patients suffering MSSA BJI will receive both administration&#xD;
      modalities and serum concentrations of cloxacillin will be determined after 3 days of II and&#xD;
      3 days of continuous infusion in a prospective, randomized, open-label, monocentric crossover&#xD;
      study design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction Staphylococcus aureus is the main causative agent of bone and joint infections&#xD;
      (BJI). More than 80% of the strains isolated in France are methicillin-susceptible (MSSA).&#xD;
      During the early phase of MSSA BJI management national and international guidelines recommend&#xD;
      the use of intra-venous type M penicillin with a dosage ranging from 100 to 200 mg/kg/day.&#xD;
      Pharmacological properties of this class of penicillin require 4 to 6 infusions by day.&#xD;
      Continuous infusion of beta-lactams is increasingly used especially in intensive care units.&#xD;
      It allows an improvement of pharmacokinetic/pharmacodynamics (PK/PD) parameters and a&#xD;
      reduction in time dedicated to infusion preparations by the nurses. However pharmacological&#xD;
      data regarding such administration is required for type M penicillin.&#xD;
&#xD;
      Design A 6-day, prospective, randomized, open-label, monocentric crossover study&#xD;
&#xD;
      Participants Twelve adult patients with MSSA BJI&#xD;
&#xD;
      Intervention Patients will be randomized in two groups: the first group will receive 3 days&#xD;
      of cloxacillin (150 mg/kg/day) through 4 intermittent infusions/day followed by 3 days of&#xD;
      cloxacillin (150 mg/kg/day) through continuous infusion (2 infusions during 12 hours). In the&#xD;
      second group the infusion modalities will be inverted and continuous infusion will be&#xD;
      preceded by a loading dose. Serum concentrations of cloxacillin will be determined at Day 3&#xD;
      and Days 6 The area under the curve / minimal inhibitory concentration ratio will be use to&#xD;
      establish the equivalence between both administration modalities.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 23, 2017</start_date>
  <completion_date type="Actual">September 18, 2018</completion_date>
  <primary_completion_date type="Actual">November 23, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T&gt; minimal inhibitory concentration</measure>
    <time_frame>Six days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: the area under the curve (AUC) / minimal inhibitory concentration</measure>
    <time_frame>Six days</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Infection</condition>
  <condition>Methicillin Susceptible Staphylococcus Aureus Infection</condition>
  <condition>Cloxacillin Treatment</condition>
  <arm_group>
    <arm_group_label>Intermittent administration of cloxacillin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>continuous administration of cloxacillin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Modification for administration mode of cloxacillin antibiotic</intervention_name>
    <description>For intermittent administration, patients will benefit from cloxacillin treatment in conventional hospitalization, in accordance with national guidelines, at a dose of 150 mg / kg per day in 4 infusions, not exceeding the maximum daily dose of 12 g / day according to.&#xD;
For continuous administration the same quantity of cloxacillin 150 mg / kg per day, without exceeding the maximum daily dose of 12 g / day, will be delivered by a self-propelled syringe in twice 12 hours. Patients randomly assigned to receive continuous administration will receive a dose of cloxacillin equivalent to the dose administered 4 times daily during iterative administration using a self-pulsating syringe. For the first day of the study, this loading dose will be subtracted from the 150 mg / kg dose to be administered continuously over the remaining 23 hours of the first day of the study and never exceed 12g / day.&#xD;
Pharmacological dosages will be performed on the third and sixth day in both arms</description>
    <arm_group_label>Intermittent administration of cloxacillin</arm_group_label>
    <arm_group_label>continuous administration of cloxacillin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Staphylococcus aureus sensitive to methicillin and to be treated with cloxacillin by&#xD;
             injectable antibiotic monotherapy For patients with Osteo-articular infection on&#xD;
             material&#xD;
&#xD;
               -  Presence of a fistula in contact with the prosthesis or implant.&#xD;
&#xD;
               -  Pus in the joint or in contact with the prosthesis or implant&#xD;
&#xD;
               -  Presence of at least 1 positive sample (1 sampling by articular puncture or 1&#xD;
                  peroperative sampling or by blood culture)&#xD;
&#xD;
               -  A histological analysis of the peri-prosthetic osteo-articular tissue which is&#xD;
                  the object of acute inflammation is a strong argument in favor of an&#xD;
                  Osteo-articular infection on material&#xD;
&#xD;
        For spondylodiscitis&#xD;
&#xD;
          -  Culture of a disco-vertebral biopsy puncture to isolate a methicillin sensitive S.&#xD;
             aureus&#xD;
&#xD;
          -  Positive haemocultures for S. aureus sensitive to methicillin with imaging examination&#xD;
             (CT or MRI of the spine) showing images of spondylodiscitis&#xD;
&#xD;
        For primitive arthritis :&#xD;
&#xD;
          -  Culture of a positive methicillin-sensitive S. aureus articular fluid puncture&#xD;
&#xD;
          -  Cultivation of a methicillin-sensitive S. aureus-positive surgical joint lavage fluid&#xD;
&#xD;
        For osteitis the diagnosis is based on the following criterion:&#xD;
&#xD;
        *Culture of surgical specimens from a focal zone of methicillin-sensitive S.&#xD;
        aureus-positive osteitis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to betalactamines&#xD;
&#xD;
          -  Taking penicillin M within 36 hours before inclusion Renal function impaired with a&#xD;
             glomerular filtration rate measured by MDRD formula of less than 30 ml / min&#xD;
&#xD;
          -  Patient with renal function expected to change within 6 days of inclusion&#xD;
&#xD;
          -  Hepatocellular insufficiency, whatever the degree&#xD;
&#xD;
             -*Methotrexate intake&#xD;
&#xD;
          -  Polytransfused (more than 2 CGR) in the previous week&#xD;
&#xD;
          -  Patients requiring resuscitation&#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>Johan Johan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Universitaire de Nice</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Nice</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>April 19, 2019</last_update_submitted>
  <last_update_submitted_qc>April 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2019</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>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Staphylococcal Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Cloxacillin</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/NCT03246360
org study id: 16-PP-04
nct id: NCT03246360
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Our objective is to establish pharmacological equivalence of intermittent and continuous
      infusion of cloxacillin during methicillin-susceptible Staphylococcus aureus (MSSA) bone and
      joint infections (BJI). Twelve patients suffering MSSA BJI will receive both administration
      modalities and serum concentrations of cloxacillin will be determined after 3 days of II and
      3 days of continuous infusion in a prospective, randomized, open-label, monocentric crossover
      study design.
Introduction Staphylococcus aureus is the main causative agent of bone and joint infections
      (BJI). More than 80% of the strains isolated in France are methicillin-susceptible (MSSA).
      During the early phase of MSSA BJI management national and international guidelines recommend
      the use of intra-venous type M penicillin with a dosage ranging from 100 to 200 mg/kg/day.
      Pharmacological properties of this class of penicillin require 4 to 6 infusions by day.
      Continuous infusion of beta-lactams is increasingly used especially in intensive care units.
      It allows an improvement of pharmacokinetic/pharmacodynamics (PK/PD) parameters and a
      reduction in time dedicated to infusion preparations by the nurses. However pharmacological
      data regarding such administration is required for type M penicillin.

      Design A 6-day, prospective, randomized, open-label, monocentric crossover study

      Participants Twelve adult patients with MSSA BJI

      Intervention Patients will be randomized in two groups: the first group will receive 3 days
      of cloxacillin (150 mg/kg/day) through 4 intermittent infusions/day followed by 3 days of
      cloxacillin (150 mg/kg/day) through continuous infusion (2 infusions during 12 hours). In the
      second group the infusion modalities will be inverted and continuous infusion will be
      preceded by a loading dose. Serum concentrations of cloxacillin will be determined at Day 3
      and Days 6 The area under the curve / minimal inhibitory concentration ratio will be use to
      establish the equivalence between both administration modalities.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T> minimal inhibitory concentration
time frame: Six days
measure: The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: the area under the curve (AUC) / minimal inhibitory concentration
time frame: Six days
arm group label: Intermittent administration of cloxacillin
arm group type: Active Comparator
arm group label: continuous administration of cloxacillin
arm group type: Experimental
intervention type: Drug
intervention name: Modification for administration mode of cloxacillin antibiotic
description: For intermittent administration, patients will benefit from cloxacillin treatment in conventional hospitalization, in accordance with national guidelines, at a dose of 150 mg / kg per day in 4 infusions, not exceeding the maximum daily dose of 12 g / day according to.
For continuous administration the same quantity of cloxacillin 150 mg / kg per day, without exceeding the maximum daily dose of 12 g / day, will be delivered by a self-propelled syringe in twice 12 hours. Patients randomly assigned to receive continuous administration will receive a dose of cloxacillin equivalent to the dose administered 4 times daily during iterative administration using a self-pulsating syringe. For the first day of the study, this loading dose will be subtracted from the 150 mg / kg dose to be administered continuously over the remaining 23 hours of the first day of the study and never exceed 12g / day.
Pharmacological dosages will be performed on the third and sixth day in both arms
arm group label: Intermittent administration of cloxacillin
arm group label: continuous administration of cloxacillin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johan Johan, MD
role: Principal Investigator
affiliation: Centre Hospitalier Universitaire de Nice
facility: 
country: France
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Staphylococcal Infections
mesh term: Anti-Bacterial Agents
mesh term: Cloxacillin
sharing ipd: No