<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/NCT03297073</url>
  </required_header>
  <id_info>
    <org_study_id>2015_61</org_study_id>
    <secondary_id>2016-002632-32</secondary_id>
    <nct_id>NCT03297073</nct_id>
  </id_info>
  <brief_title>Paracetamol Metabolism Research in Postoperative Hepatic Surgery</brief_title>
  <acronym>PARAFOI</acronym>
  <official_title>Paracetamol Metabolism Research in Postoperative Hepatic Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The main objective of this study was to evaluate the 5-day kinetics of plasma paracetamol&#xD;
      levels in postoperative major hepatic surgery (resection greater than or equal to three&#xD;
      hepatic segments) compared with less extensive liver resection and hepatic re-intervention.&#xD;
      The clearance of indocyanine green is a marker of hepatic perfusion but also of the proper&#xD;
      hepatocyte functioning, if hemodynamic conditions are stable.&#xD;
&#xD;
      Some patients may be operated on up to four or five times in the liver. Moreover, these&#xD;
      patients probably present an increased risk of postoperative hepatocellular insufficiency due&#xD;
      to a quantitative and qualitative decrease in their hepatic parenchyma. It is therefore&#xD;
      interesting to evaluate the use of paracetamol in this situation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 20, 2016</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">January 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dosing and kinetics of paracetamolemia</measure>
    <time_frame>during the 5 post-operative days</time_frame>
    <description>this determination of the plasma paracetamol dosage on D0 (H6: 6 hours after the end of the procedure) and D1 D2 D3 D4 D5 (samples taken at 6 am each day just before the injection of paracetamol whose administration hours will be 6h 12h 18h and midnight)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dosage of urinary metabolites of paracetamol (paracetamol sulphate, paracetamol glucuronide)</measure>
    <time_frame>At Day 1, day 3, day 5 post operative</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosage of N-acetyl-cysteinyl paracetamol ( NAPQI)</measure>
    <time_frame>At Day 1, day 3, day 5 post operative</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with paracetamolemia greater than 60 mg / mL</measure>
    <time_frame>during the 5 post-operative days</time_frame>
    <description>60mj/ml = paracetamol toxicity threshold according to Prescott diagram to 6 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Disappearance Rate of indocyanine green (TDP-ICG) by LiMon®</measure>
    <time_frame>At Day 1, day 3, day 5 post operative</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of postoperative hepatocellular insufficiency</measure>
    <time_frame>at day 5</time_frame>
    <description>The postoperative hepatocellular insufficiency according to the 50/50 criteria (TP &lt;50% and bilirubinemia&gt; 50 μmol / L on the 5th day) according to the type of hepatic resection (with or without clamping, continuous or discontinuous, duration intervention).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of complications related to hepatic failure</measure>
    <time_frame>at day 5</time_frame>
    <description>the complications related to hepatic failure not falling within the &quot;50/50&quot; criteria: jaundice, hepatic encephalopathy, coagulation disorders, ascites, cytolysis, cholestasis.&#xD;
Other medical and surgical. Duration of hospitalization in perioperative intensive care and duration of total hospitalization.&#xD;
Mortality at 30 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospitalization in perioperative intensive care</measure>
    <time_frame>at 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of total hospitalization.</measure>
    <time_frame>at 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>at 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite characteristics of surgery.</measure>
    <time_frame>at 30 days</time_frame>
    <description>Characteristics of surgery: duration of intervention, numbers, duration and types of vascular clamping, detailed description of the type of liver resection performed, quantification of bleeding.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Paracetamol Causing Adverse Effects in Therapeutic Use</condition>
  <condition>Hepatic Disease</condition>
  <arm_group>
    <arm_group_label>major hepatic surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>resection greater than or equal to three hepatic segments</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hepatic surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>resection less than three hepatic segments</description>
  </arm_group>
  <arm_group>
    <arm_group_label>hepatic surgery recovery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paracetamol</intervention_name>
    <description>Paracetamol 1000 mg will be administered 30 minutes before the end of the procedure and then every 6 hours systematically at the following times: 6h / 12h / 18h / 00h.&#xD;
The analgesic treatment after hepatectomy with paracetamol will be maintained for at least 5 days in all patients in parenteral form</description>
    <arm_group_label>hepatic surgery</arm_group_label>
    <arm_group_label>hepatic surgery recovery</arm_group_label>
    <arm_group_label>major hepatic surgery</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>hepatic surgery</intervention_name>
    <arm_group_label>hepatic surgery</arm_group_label>
    <arm_group_label>hepatic surgery recovery</arm_group_label>
    <arm_group_label>major hepatic surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients requiring surgery for hepatic resection by initiation under chest or&#xD;
             laparoscopic without hepatocellular insufficiency,&#xD;
&#xD;
          -  ASA score 1 to 3 (American Society of Anesthesiologists score ranging from 1 to 5&#xD;
             evaluating the preoperative health status of a patient),&#xD;
&#xD;
          -  Verification of the understanding of the protocol,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients classified ASA 4 or 5,&#xD;
&#xD;
          -  Allergy or intolerance to indocyanine green&#xD;
&#xD;
          -  Allergy or intolerance to paracetamol,&#xD;
&#xD;
          -  Taking of paracetamol the week before the intervention,&#xD;
&#xD;
          -  Patient less than 60 Kgs (because decrease of doses of paracetamol),&#xD;
&#xD;
          -  Emergency surgery, palliative surgery and surgical recovery,&#xD;
&#xD;
          -  Psychic disorder,&#xD;
&#xD;
          -  Contra-indication to a treatment used during the study,&#xD;
&#xD;
          -  incapable major,&#xD;
&#xD;
          -  Intellectual incapacity preventing proper understanding of the protocol,&#xD;
&#xD;
          -  Pregnant or nursing woman,&#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>Gilles Lebuffe, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gilles Lebuffe, MD,PhD</last_name>
    <phone>3 20 44 41 12</phone>
    <phone_ext>+33</phone_ext>
    <email>gilles.lebuffe@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Huriez, CHRU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Gilles Lebuffe, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>October 10, 2019</last_update_submitted>
  <last_update_submitted_qc>October 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 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>Liver Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</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/NCT03297073
org study id: 2015_61
secondary id: 2016-002632-32
nct id: NCT03297073
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The main objective of this study was to evaluate the 5-day kinetics of plasma paracetamol
      levels in postoperative major hepatic surgery (resection greater than or equal to three
      hepatic segments) compared with less extensive liver resection and hepatic re-intervention.
      The clearance of indocyanine green is a marker of hepatic perfusion but also of the proper
      hepatocyte functioning, if hemodynamic conditions are stable.

      Some patients may be operated on up to four or five times in the liver. Moreover, these
      patients probably present an increased risk of postoperative hepatocellular insufficiency due
      to a quantitative and qualitative decrease in their hepatic parenchyma. It is therefore
      interesting to evaluate the use of paracetamol in this situation.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Dosing and kinetics of paracetamolemia
time frame: during the 5 post-operative days
description: this determination of the plasma paracetamol dosage on D0 (H6: 6 hours after the end of the procedure) and D1 D2 D3 D4 D5 (samples taken at 6 am each day just before the injection of paracetamol whose administration hours will be 6h 12h 18h and midnight)
measure: Dosage of urinary metabolites of paracetamol (paracetamol sulphate, paracetamol glucuronide)
time frame: At Day 1, day 3, day 5 post operative
measure: Dosage of N-acetyl-cysteinyl paracetamol ( NAPQI)
time frame: At Day 1, day 3, day 5 post operative
measure: Percentage of patients with paracetamolemia greater than 60 mg / mL
time frame: during the 5 post-operative days
description: 60mj/ml = paracetamol toxicity threshold according to Prescott diagram to 6 hours
measure: Plasma Disappearance Rate of indocyanine green (TDP-ICG) by LiMon®
time frame: At Day 1, day 3, day 5 post operative
measure: Rate of postoperative hepatocellular insufficiency
time frame: at day 5
description: The postoperative hepatocellular insufficiency according to the 50/50 criteria (TP <50% and bilirubinemia> 50 μmol / L on the 5th day) according to the type of hepatic resection (with or without clamping, continuous or discontinuous, duration intervention).
measure: Occurrence of complications related to hepatic failure
time frame: at day 5
description: the complications related to hepatic failure not falling within the "50/50" criteria: jaundice, hepatic encephalopathy, coagulation disorders, ascites, cytolysis, cholestasis.
Other medical and surgical. Duration of hospitalization in perioperative intensive care and duration of total hospitalization.
Mortality at 30 days.
measure: Duration of hospitalization in perioperative intensive care
time frame: at 30 days
measure: Duration of total hospitalization.
time frame: at 30 days
measure: Mortality
time frame: at 30 days
measure: Composite characteristics of surgery.
time frame: at 30 days
description: Characteristics of surgery: duration of intervention, numbers, duration and types of vascular clamping, detailed description of the type of liver resection performed, quantification of bleeding.
arm group label: major hepatic surgery
arm group type: Experimental
description: resection greater than or equal to three hepatic segments
arm group label: hepatic surgery
arm group type: Experimental
description: resection less than three hepatic segments
arm group label: hepatic surgery recovery
arm group type: Experimental
intervention type: Drug
intervention name: paracetamol
description: Paracetamol 1000 mg will be administered 30 minutes before the end of the procedure and then every 6 hours systematically at the following times: 6h / 12h / 18h / 00h.
The analgesic treatment after hepatectomy with paracetamol will be maintained for at least 5 days in all patients in parenteral form
arm group label: hepatic surgery
arm group label: hepatic surgery recovery
arm group label: major hepatic surgery
intervention type: Procedure
intervention name: hepatic surgery
arm group label: hepatic surgery
arm group label: hepatic surgery recovery
arm group label: major hepatic surgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilles Lebuffe, MD,PhD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Gilles Lebuffe, MD,PhD
phone: 3 20 44 41 12
phone ext: +33
email: gilles.lebuffe@chru-lille.fr
facility: 
status: Recruiting
investigator: 
country: France
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Acetaminophen
sharing ipd: No