<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/NCT03306290</url>
  </required_header>
  <id_info>
    <org_study_id>2017-A01285-48</org_study_id>
    <nct_id>NCT03306290</nct_id>
  </id_info>
  <brief_title>Serum Concentration of CEFOxitin Used for Antibiotic Prophylaxis in Obese Patients Undergoing BARiatric Surgery</brief_title>
  <acronym>CEFOBAR</acronym>
  <official_title>An Evaluation of Serum Concentration of CEFOxitin Used for Antibiotic Prophylaxis in Severely and Morbidly Obese Patients Undergoing BARiatric Surgery (CEFOBAR)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Hospital, Nancy, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central Hospital, Nancy, France</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>
      Obesity is a pandemic problem in modern societies. Bariatric surgery (gastric by-pass and&#xD;
      sleeve gastrectomy) has emerged as an efficient treatment to reduce morbidity and mortality&#xD;
      related to obesity. Obesity and bariatric surgery are known to be risk factors of surgical&#xD;
      site infections (SSI). The occurrence of SSI increases health cost and the duration of&#xD;
      hospitalization. However, an appropriate antibiotic prophylaxis has been shown to reduce SSI.&#xD;
      As recommended by several national societies, the antibiotic prophylaxis dose should be&#xD;
      increased in the severely obese population. However, this recommendation lies on a low level&#xD;
      of evidence. Besides, great disparities regarding obese patient antibiotic prophylaxis exist&#xD;
      between countries and adequate doses are still not clearly defined. In France, for instance,&#xD;
      the intravenous second generation cephalosporin CEFOXITIN is used for antibiotic prophylaxis&#xD;
      in bariatric surgery at the initial loading dose of 4g (2-fold that of non-obese population)&#xD;
      at the beginning of surgery.&#xD;
&#xD;
      Obese patients have increased risk of under-dosage due to modification of their&#xD;
      pharmacokinetics (fat/lean mass, distribution volume, renal clearance, etc.). Only few&#xD;
      studies, all investigating a low amount of patients, evaluated the appropriateness of&#xD;
      intraoperative antibiotic prophylaxis dosage of different betalactam and cephalosporin in the&#xD;
      obese population. This population was more likely to be under-dosed.&#xD;
&#xD;
      The aim of this study is to analyse the appropriateness of the reference dose of intravenous&#xD;
      Cefoxitin used as antibiotic prophylaxis in severely obese patients undergoing bariatric&#xD;
      surgery. This will be a 2-year prospective monocentric study held in the University Hospital&#xD;
      of Nancy, France. A large group of obese patients (~300) will be included. Serial serum&#xD;
      concentration measurements of Cefoxitin will be performed before, during, and at skin closure&#xD;
      of the bariatric surgery. This study will give insights in pharmacokinetics of the antibiotic&#xD;
      prophylaxis in the obese population and will help to determine the initial dosage and the&#xD;
      optimal method for antibiotic prophylaxis administration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">August 9, 2018</completion_date>
  <primary_completion_date type="Actual">June 30, 2018</primary_completion_date>
  <phase>N/A</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum concentration of Cefoxitin at the beginning and end of the surgery with one extra measurement at halfway surgery</measure>
    <time_frame>baseline</time_frame>
    <description>Blood samples will be put at low temperature for transportation and then analysed by chromatographic method</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identification of factors that may be associated with the risk of under-dosage</measure>
    <time_frame>baseline</time_frame>
    <description>effect of creatinine clearance on cefoxitine concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of factors that may be associated with the risk of under-dosage</measure>
    <time_frame>baseline</time_frame>
    <description>effect of age of the patient on cefoxitine concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of factors that may be associated with the risk of under-dosage</measure>
    <time_frame>baseline</time_frame>
    <description>effect of lenght of surgery on cefoxitine concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of factors that may be associated with the risk of under-dosage</measure>
    <time_frame>baseline</time_frame>
    <description>effect of type of surgery on cefoxitine concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters: drug clearance</measure>
    <time_frame>baseline</time_frame>
    <description>These parameters will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.&#xD;
o Clearance: Cl=k x Vd</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: volume of distribution</measure>
    <time_frame>baseline</time_frame>
    <description>This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.&#xD;
o Volume of distribution: D0/C0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: half-life</measure>
    <time_frame>baseline</time_frame>
    <description>This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.&#xD;
o Half-life: t1/2=ln2/k</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: area under curve,</measure>
    <time_frame>baseline</time_frame>
    <description>This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.&#xD;
o Area under curve: AUC=C0/k</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameter: elimination rate</measure>
    <time_frame>baseline</time_frame>
    <description>This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.&#xD;
o Elimination rate: k=(LnC0-LnC2)/(t2-t0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of superficial incisional surgical site infection (SSI) at 30 days</measure>
    <time_frame>up to 30 days after surgery</time_frame>
    <description>o Superficial incisional SSI: at 30 days defined by:&#xD;
Date of event for infection occurs within 30 days after any operative procedure AND involves only skin and subcutaneous tissue of the incision AND the patient has at least one of the following:&#xD;
purulent drainage from the superficial incision,&#xD;
organisms identified from an aseptically-obtained specimen,&#xD;
from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment (e.g., not Active Surveillance Culture/Testing (ASC/AST),&#xD;
superficial incision that is deliberately opened by a surgeon, attending physician or other designee and culture or non-culture based testing is not performed AND patient has at least one of the following signs or symptoms: pain or tenderness;localized swelling; erythema; or heat,&#xD;
diagnosis of a superficial incisional SSI by the surgeon or attending physician or other designee.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of deep incisional surgical site infection (SSI) at 30 days</measure>
    <time_frame>up to 30 days after surgery</time_frame>
    <description>Deep incisional SSI at 30 days defined by:&#xD;
date of event for infection occurs within 30 days after the operative procedure AND involves deep soft tissues of the incision (e.g., fascial and muscle layers) AND patient has at least one of the following:&#xD;
purulent drainage from the deep incision,&#xD;
a deep incision that spontaneously dehisces, or is deliberately opened or aspirated by a surgeon, attending physician or other designee and organism is identified by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment (e.g., not Active Surveillance Culture/Testing (ASC/AST) or culture or non-culture based microbiologic testing method is not performed AND patient has at least one of the following signs or symptoms: fever (&gt;38°C); localized pain or tenderness.&#xD;
an abscess or other evidence of infection involving the deep incision that is detected on gross anatomical or histopathologic exam, or imaging test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of organ/space surgical site infection (SSI) at 30 days</measure>
    <time_frame>up to 30 days after surgery</time_frame>
    <description>Organ/Space SSI at 30 days defined by:&#xD;
Date of event for infection occurs within 30 after the operative procedure AND infection involves any part of the body deeper than the fascial/muscle layers, that is opened or manipulated during the operative procedure AND patient has at least one of the following:&#xD;
purulent drainage from a drain that is placed into the organ/space&#xD;
organisms are identified from an fluid or tissue in the organ/space by a culture or non-culture based microbiologic testing method&#xD;
an abscess or other evidence of infection involving the organ/space that is detected on gross anatomical or histopathologic exam, or imaging test evidence suggestive of infection AND meets at least one criterion for a specific organ/space infection site listed: intraabdominal infection, not specified elsewhere including gallbladder, bile ducts, liver, spleen, pancreas, peritoneum, subphrenic or subdiaphragmatic space</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Obese</condition>
  <condition>Antibiotic Prophylaxis</condition>
  <condition>Bariatric Surgery Candidate</condition>
  <arm_group>
    <arm_group_label>Bariatric surgery candidate</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients included in this study belong to this arm and put up with intervention &quot;Serum dosage of antibiotic prophylaxis CEFOXITIN&quot;</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Serum dosage of antibiotic prophylaxis CEFOXITIN</intervention_name>
    <description>Three blood samples will be collected. These samples are specific for the research, and will be performed on the forearm opposite to the one used for Cefoxitin infusion.&#xD;
Blood sample at the start of surgery (t0): at the end of the Cefoxitin infusion (~30 min), 1 tube (5 ml) of blood will be withdrawn&#xD;
Blood sample at half way surgery (t1): 1 tube (5 ml) of blood will be withdrawn (if applicable)&#xD;
Blood sample at skin closure (t2): 1 tube (5 ml) of blood will be withdrawn</description>
    <arm_group_label>Bariatric surgery candidate</arm_group_label>
    <other_name>Drug dosage</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years-old,&#xD;
&#xD;
          -  Severely obese patient with a BMI ≥ 35 kg.m-2,&#xD;
&#xD;
          -  Scheduled bariatric surgery: gastric by-pass or sleeve gastrectomy,&#xD;
&#xD;
          -  Affiliated to social security,&#xD;
&#xD;
          -  The patient is able to consent to clinical research and has received all information&#xD;
             on the study design/protocol,&#xD;
&#xD;
          -  Signed/written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refuse to consent to the study or the patient is unable to consent,&#xD;
&#xD;
          -  Allergy/Anaphylaxis to beta-lactam (ß-lactam) antibiotics either proven or suspected,&#xD;
&#xD;
          -  Pregnancy,&#xD;
&#xD;
          -  Persons deprived of their liberty by judicial or administrative decision,&#xD;
&#xD;
          -  Urgent or emergent surgery.&#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>El Mehdi SIAGHY</last_name>
    <role>Study Director</role>
    <affiliation>Central Hospital, Nancy, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Central Hospital</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <zip>54500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>August 27, 2018</last_update_submitted>
  <last_update_submitted_qc>August 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Obese</keyword>
  <keyword>Bariatric surgery</keyword>
  <keyword>Antibiotic prophylaxis</keyword>
  <keyword>Cefoxitin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</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>Cefoxitin</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/NCT03306290
org study id: 2017-A01285-48
nct id: NCT03306290
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Obesity is a pandemic problem in modern societies. Bariatric surgery (gastric by-pass and
      sleeve gastrectomy) has emerged as an efficient treatment to reduce morbidity and mortality
      related to obesity. Obesity and bariatric surgery are known to be risk factors of surgical
      site infections (SSI). The occurrence of SSI increases health cost and the duration of
      hospitalization. However, an appropriate antibiotic prophylaxis has been shown to reduce SSI.
      As recommended by several national societies, the antibiotic prophylaxis dose should be
      increased in the severely obese population. However, this recommendation lies on a low level
      of evidence. Besides, great disparities regarding obese patient antibiotic prophylaxis exist
      between countries and adequate doses are still not clearly defined. In France, for instance,
      the intravenous second generation cephalosporin CEFOXITIN is used for antibiotic prophylaxis
      in bariatric surgery at the initial loading dose of 4g (2-fold that of non-obese population)
      at the beginning of surgery.

      Obese patients have increased risk of under-dosage due to modification of their
      pharmacokinetics (fat/lean mass, distribution volume, renal clearance, etc.). Only few
      studies, all investigating a low amount of patients, evaluated the appropriateness of
      intraoperative antibiotic prophylaxis dosage of different betalactam and cephalosporin in the
      obese population. This population was more likely to be under-dosed.

      The aim of this study is to analyse the appropriateness of the reference dose of intravenous
      Cefoxitin used as antibiotic prophylaxis in severely obese patients undergoing bariatric
      surgery. This will be a 2-year prospective monocentric study held in the University Hospital
      of Nancy, France. A large group of obese patients (~300) will be included. Serial serum
      concentration measurements of Cefoxitin will be performed before, during, and at skin closure
      of the bariatric surgery. This study will give insights in pharmacokinetics of the antibiotic
      prophylaxis in the obese population and will help to determine the initial dosage and the
      optimal method for antibiotic prophylaxis administration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Serum concentration of Cefoxitin at the beginning and end of the surgery with one extra measurement at halfway surgery
time frame: baseline
description: Blood samples will be put at low temperature for transportation and then analysed by chromatographic method
measure: Identification of factors that may be associated with the risk of under-dosage
time frame: baseline
description: effect of creatinine clearance on cefoxitine concentration
measure: Identification of factors that may be associated with the risk of under-dosage
time frame: baseline
description: effect of age of the patient on cefoxitine concentration
measure: Identification of factors that may be associated with the risk of under-dosage
time frame: baseline
description: effect of lenght of surgery on cefoxitine concentration
measure: Identification of factors that may be associated with the risk of under-dosage
time frame: baseline
description: effect of type of surgery on cefoxitine concentration
measure: Pharmacokinetic parameters: drug clearance
time frame: baseline
description: These parameters will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.
o Clearance: Cl=k x Vd
measure: Pharmacokinetic parameter: volume of distribution
time frame: baseline
description: This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.
o Volume of distribution: D0/C0
measure: Pharmacokinetic parameter: half-life
time frame: baseline
description: This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.
o Half-life: t1/2=ln2/k
measure: Pharmacokinetic parameter: area under curve,
time frame: baseline
description: This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.
o Area under curve: AUC=C0/k
measure: Pharmacokinetic parameter: elimination rate
time frame: baseline
description: This parameter will be calculated according to the initial concentration (C0) and the final concentration (C2) measured at t0 and t2 respectively. A corrective factor will be applied according to the halfway surgery serum concentration of Cefoxitin.
o Elimination rate: k=(LnC0-LnC2)/(t2-t0)
measure: Incidence of superficial incisional surgical site infection (SSI) at 30 days
time frame: up to 30 days after surgery
description: o Superficial incisional SSI: at 30 days defined by:
Date of event for infection occurs within 30 days after any operative procedure AND involves only skin and subcutaneous tissue of the incision AND the patient has at least one of the following:
purulent drainage from the superficial incision,
organisms identified from an aseptically-obtained specimen,
from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment (e.g., not Active Surveillance Culture/Testing (ASC/AST),
superficial incision that is deliberately opened by a surgeon, attending physician or other designee and culture or non-culture based testing is not performed AND patient has at least one of the following signs or symptoms: pain or tenderness;localized swelling; erythema; or heat,
diagnosis of a superficial incisional SSI by the surgeon or attending physician or other designee.
measure: Incidence of deep incisional surgical site infection (SSI) at 30 days
time frame: up to 30 days after surgery
description: Deep incisional SSI at 30 days defined by:
date of event for infection occurs within 30 days after the operative procedure AND involves deep soft tissues of the incision (e.g., fascial and muscle layers) AND patient has at least one of the following:
purulent drainage from the deep incision,
a deep incision that spontaneously dehisces, or is deliberately opened or aspirated by a surgeon, attending physician or other designee and organism is identified by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment (e.g., not Active Surveillance Culture/Testing (ASC/AST) or culture or non-culture based microbiologic testing method is not performed AND patient has at least one of the following signs or symptoms: fever (>38°C); localized pain or tenderness.
an abscess or other evidence of infection involving the deep incision that is detected on gross anatomical or histopathologic exam, or imaging test.
measure: Incidence of organ/space surgical site infection (SSI) at 30 days
time frame: up to 30 days after surgery
description: Organ/Space SSI at 30 days defined by:
Date of event for infection occurs within 30 after the operative procedure AND infection involves any part of the body deeper than the fascial/muscle layers, that is opened or manipulated during the operative procedure AND patient has at least one of the following:
purulent drainage from a drain that is placed into the organ/space
organisms are identified from an fluid or tissue in the organ/space by a culture or non-culture based microbiologic testing method
an abscess or other evidence of infection involving the organ/space that is detected on gross anatomical or histopathologic exam, or imaging test evidence suggestive of infection AND meets at least one criterion for a specific organ/space infection site listed: intraabdominal infection, not specified elsewhere including gallbladder, bile ducts, liver, spleen, pancreas, peritoneum, subphrenic or subdiaphragmatic space
arm group label: Bariatric surgery candidate
arm group type: Other
description: Patients included in this study belong to this arm and put up with intervention "Serum dosage of antibiotic prophylaxis CEFOXITIN"
intervention type: Drug
intervention name: Serum dosage of antibiotic prophylaxis CEFOXITIN
description: Three blood samples will be collected. These samples are specific for the research, and will be performed on the forearm opposite to the one used for Cefoxitin infusion.
Blood sample at the start of surgery (t0): at the end of the Cefoxitin infusion (~30 min), 1 tube (5 ml) of blood will be withdrawn
Blood sample at half way surgery (t1): 1 tube (5 ml) of blood will be withdrawn (if applicable)
Blood sample at skin closure (t2): 1 tube (5 ml) of blood will be withdrawn
arm group label: Bariatric surgery candidate
other name: Drug dosage
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: El Mehdi SIAGHY
role: Study Director
affiliation: Central Hospital, Nancy, France
facility: 
country: France
responsible party type: Sponsor
mesh term: Obesity
mesh term: Anti-Bacterial Agents
mesh term: Cefoxitin
sharing ipd: No