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Peritoneal Diffusion and Efficacy of Antibiotic Therapy in Pediatric Peritonitis (DIFFUPERPED)

Primary Purpose

Peritonitis, Appendicitis, Children, Only

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Dosage of serum and peritoneal of the betalactam used for antibiotic treatment
Sponsored by
Central Hospital, Nancy, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Peritonitis focused on measuring Children Peritonitis, Antibiotic diffusion, Pharmacocinetic study

Eligibility Criteria

3 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • diagnosis of intra-abdominal infection : localized or generalized peritonitis secondary to appendix

Exclusion Criteria:

  • betalactams allergy
  • peritonitis with other etiology than appendix
  • antibiotic treatment longer than 24h

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Other

    Arm Label

    Pediatric Peritonitis

    Arm Description

    Patient (from 3 to 17 years-old) treated for appendicular peritonitis. It includes surgical treatment (appendicectomy, peritoneal toilet) and antibiotherapy according to French recommendation.

    Outcomes

    Primary Outcome Measures

    antibiotic concentration
    Serum betalactams concentrations at different times
    antibiotic concentration
    Peritonal betalactams concentrations at different times

    Secondary Outcome Measures

    Determine elimination rate constant Kel
    It is the first order rate constant describing drug elimination from the body.
    Determine estimated initial concentrationf C0
    Initial concentration of antibiotic in the body
    Determine Area Under the Curve AUC.
    It is the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time.
    Determine Half-life
    It is a pharmacokinetic parameter that is defined as the time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%.
    Determine distribution volume
    It is a pharmacokinetic parameter representing an individual drug's propensity to either remain in the plasma or redistribute to other tissue compartments.
    Determine Clearance or betalactams in children
    It is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time.
    Evaluate the relationship between serum and peritoneal concentrations of beta-lactam
    Determination of the antibiotic diffusion coefficient through the peritoneal membrane : difference between serum concentration and peritoneal concentration of betalactam
    Proportion of different bacteria
    Describe the local bacterial ecology
    Proportion of sensitive and resistant germs to betalactam antibiotics
    Describe the local bacterial ecology
    Description of minimal inhibition concentration for bacterias
    Describe the local bacterial ecology
    Factors associated with an antibiotic under-dosage
    Factors statistically associated with antibiotic under dosage defined by serum and peritonal concentrations < 4*MIC using multivariate analysis.
    Factors associated with an antibiotic overdose
    Factors statistically associated with antibiotic overdose defined by serum and peritonal concentrations >10*MIC using multivariate analysis.
    Evaluation of duration of hospitalization
    Describe the clinical efficacy of antibiotic protocol
    Mean delay for apyrexia
    Describe the clinical efficacy of antibiotic protocol
    Clinical complications
    Describe the clinical efficacy of antibiotic protocol

    Full Information

    First Posted
    January 20, 2022
    Last Updated
    March 24, 2022
    Sponsor
    Central Hospital, Nancy, France
    Collaborators
    PAPE Elise
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05308849
    Brief Title
    Peritoneal Diffusion and Efficacy of Antibiotic Therapy in Pediatric Peritonitis
    Acronym
    DIFFUPERPED
    Official Title
    Peritoneal Diffusion and Efficacy of Antibiotic Therapy in Pediatric Peritonitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 31, 2022 (Anticipated)
    Primary Completion Date
    March 31, 2024 (Anticipated)
    Study Completion Date
    June 30, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Central Hospital, Nancy, France
    Collaborators
    PAPE Elise

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a pilote monocentric prospective study about pediatric peritonitis and antibiotics pharmacokinetic and pharmacodynamic. The investigators will include 41 patients between 3 and 17 years-old during 2 years in the University Hospital of Nancy. The aim of this study is to determine if the beta-lactam dosages in children recommended by the guidelines for management of intra-abdominal infections permitted the achievement of adequatly serum and peritoneal concentrations in the medical and surgical management of peritonitis. The investigators will collected serum and peritoneal fluid samples at 3 different times: peritoneal incision, end of surgery, 2 days and 5 days after surgery in order to compare the concentrations and the minimal inhibitor concentration of bacteria. The hypothesis is that of a serum and peritoneal antibiotic under dosage.
    Detailed Description
    Pediatric population with localized or generalized appendicular peritonitis with surgical management at the Nancy University Hospital. Patients are usually taken in emergency at the Pediatric Emergency Department (Children's Hospital, CHRU Nancy). The diagnosis of peritonitis is then made or confirmed by clinical examination and paraclinical tests (biology and imaging). Written informed consent is obtained from one of the parental authority holders, allowing inclusion in the study. An information document adapted to the child's understanding will also be sent to him/her. The child's non-opposition will be sought if he/she is old enough to understand. The information will be given jointly to the child and to the legal guardians present at the patient's bed at the time of diagnosis of peritonitis. The reflection period will correspond to the interval between this information and the management in the operating room. This may vary depending on the occupation of the operating room. The diagnosis of appendicular peritonitis is made by the surgeon (routine care). The child is included. Antibiotic therapy is started IV according to the protocol in force at the CHRU (routine care): - Cefotaxime (200 mg/kg/d, 4 IV administrations) + Metronidazole (20-30 mg/kg/d, 3 IV administrations)+/-Gentamicin (3-8 mg/kg/d IV) Specific biological samples and collections are taken for the research: A blood sample (1mL) (S0) after injection of the antibiotic and before appendicular section, non-invasive because performed on peripheral venous route. A blood sample (1mL) (S1) at the end of the operation, either when the peripheral venous route is placed if possible (non-invasive), otherwise at the periphery (invasive). If a drainage of the peritoneal cavity is in place, a non-invasive collection of peritoneal fluid (5 mL) on the drain will be performed (P1) at D2. If generalized peritonitis, an additional blood collection (1mL) at D5 (S2) during the biological check-up (routine care). If an abdominal drainage is still in place, a non-invasive collection of peritoneal fluid (5mL) on drain will be performed (P2). At D5, the patients are under appropriate antibiotic therapy. Specifically for research, betalactam assays are performed on S0, S1, S2, P0, P1 and P2 once all samples have been sent to Pharmacology. Bacteriological analyses are performed on P0 (routine care), P1 and P2 in real time. The following specific data will be collected: time of first antibiotic administration, time of sampling (S0, S1 and P0), time of surgery start. Data concerning antibiotic therapy (dosage, frequency of administration) will be collected during the entire hospitalization period as well as the time of the other samples if applicable (S2, P1 and P2). Clinical and biological data are collected, including the visit at 4-6 weeks after discharge. (In routine care, a visit at 1 month post-op is performed). The investigator looks for AEs or SAEs. At the end of this post-operative visit, the patient is discharged from the study. The volume of blood collected in the framework of the research is estimated at 3mL, i.e. less than 2.5% of the total blood volume over the inclusion period. The maximum total volume collected is 24 mL (6 mL for research, 18 mL for care, i.e. 3 samples of CBC, blood ionogram and CRP). Blood and peritoneal samples : The 3 blood samples as well as the 2 (possibly 3) peritoneal samples will be taken by a nurse and will be placed in a specific bag. Each sampling time will be clearly identified on the sample and a traceability form will be completed and sent to the Pharmacology and Toxicology laboratory.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Peritonitis, Appendicitis, Children, Only, Antibiotic Toxicity
    Keywords
    Children Peritonitis, Antibiotic diffusion, Pharmacocinetic study

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    41 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Pediatric Peritonitis
    Arm Type
    Other
    Arm Description
    Patient (from 3 to 17 years-old) treated for appendicular peritonitis. It includes surgical treatment (appendicectomy, peritoneal toilet) and antibiotherapy according to French recommendation.
    Intervention Type
    Other
    Intervention Name(s)
    Dosage of serum and peritoneal of the betalactam used for antibiotic treatment
    Intervention Description
    All patients will have antibiotherapy according to French recommendation. Antibiotics recommended are: cefotaxime 200mg/kg/d / OR amoxicillin/clavulanic acid 25 mg/kg x 3 /d OR piperacilline/tazobactam 100 mg/kg/d Blood samples will be collected before surgery and after surgery (for all patients). Peritoneal sample will be collected during surgery (for all patients). Additionnal optionnal blood sample could be collected on Day 5 after surgery. Additionnal optionnal peritoneal samples could be collected on Day 2 and Day 5. Dosage of serum and peritoneal of the used betalactam will be performed by High Performance Liquid Chromatography Method
    Primary Outcome Measure Information:
    Title
    antibiotic concentration
    Description
    Serum betalactams concentrations at different times
    Time Frame
    Peritoneal incision, end of surgery, Day+5 after surgery if systemic peritonitis,
    Title
    antibiotic concentration
    Description
    Peritonal betalactams concentrations at different times
    Time Frame
    During surgery, Day+2 after surgery if drain peritonal, Day+5 after surgery if systemic peritonitis,
    Secondary Outcome Measure Information:
    Title
    Determine elimination rate constant Kel
    Description
    It is the first order rate constant describing drug elimination from the body.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Determine estimated initial concentrationf C0
    Description
    Initial concentration of antibiotic in the body
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Determine Area Under the Curve AUC.
    Description
    It is the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Determine Half-life
    Description
    It is a pharmacokinetic parameter that is defined as the time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Determine distribution volume
    Description
    It is a pharmacokinetic parameter representing an individual drug's propensity to either remain in the plasma or redistribute to other tissue compartments.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Determine Clearance or betalactams in children
    Description
    It is a pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Evaluate the relationship between serum and peritoneal concentrations of beta-lactam
    Description
    Determination of the antibiotic diffusion coefficient through the peritoneal membrane : difference between serum concentration and peritoneal concentration of betalactam
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Proportion of different bacteria
    Description
    Describe the local bacterial ecology
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Proportion of sensitive and resistant germs to betalactam antibiotics
    Description
    Describe the local bacterial ecology
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Description of minimal inhibition concentration for bacterias
    Description
    Describe the local bacterial ecology
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Factors associated with an antibiotic under-dosage
    Description
    Factors statistically associated with antibiotic under dosage defined by serum and peritonal concentrations < 4*MIC using multivariate analysis.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Factors associated with an antibiotic overdose
    Description
    Factors statistically associated with antibiotic overdose defined by serum and peritonal concentrations >10*MIC using multivariate analysis.
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Evaluation of duration of hospitalization
    Description
    Describe the clinical efficacy of antibiotic protocol
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Mean delay for apyrexia
    Description
    Describe the clinical efficacy of antibiotic protocol
    Time Frame
    Statistical analysis after 2 years of inclusion
    Title
    Clinical complications
    Description
    Describe the clinical efficacy of antibiotic protocol
    Time Frame
    Statistical analysis after 2 years of inclusion

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Years
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: diagnosis of intra-abdominal infection : localized or generalized peritonitis secondary to appendix Exclusion Criteria: betalactams allergy peritonitis with other etiology than appendix antibiotic treatment longer than 24h

    12. IPD Sharing Statement

    Learn more about this trial

    Peritoneal Diffusion and Efficacy of Antibiotic Therapy in Pediatric Peritonitis

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