Pharmacokinetic Study on Echinocandins for Patients With Septic Shock Following Secondary Peritonitis

Study Overview
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Brief Summary
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The main objective of this study is to describe the pharmacokinetics of the prescribed echinocandins for septic shock with secondary peritonitis for which intra-abdominal fungal infection is suspected or proven.

Detailed Description
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The secondary objectives of this study are: Determine whether the current recommended doses of caspofungin achieve the Pharmacokinetic/Pharmacodynamic (PK/PD) target for this molecule. Determine whether the current recommended doses of micafungin achieve the PK / PD target for this molecule Describe the peritoneal concentrations of echinocandins in secondary peritonitis complicated with septic shock Identify via modeling PK / PD parameters and based on monte Carlo simulations the optimal dosing regimen for caspofungin and micafungin in this population

Official Title
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Pharmacokinetic Study on Echinocandins for Patients With Septic Shock Following Secondary Peritonitis

Conditions
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Septic Shock, Peritonitis

Intervention / Treatment
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* Drug: Echinocandins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The emergency inclusion procedure was correctly applied according to French law (signature of consent form by a patient-designated trusted person or a family member, or a medical decision to proceed with patient inclusion if the latter two persons are unavailable) ---- OR ---- signature of the consent form by the patient The patient must be insured or beneficiary of a health insurance plan The patient is 18 years of age or older The patient has beed admitted to the ICU for septic shock accompanying secondary peritonitis Patient requiring antifungal treatment via echinocandins (caspofungin or micafungin) A venous or arterial access for blood sampling is already in place for routine care Exclusion Criteria: The patient is participating in an interventional study that may affect the results of the present study, or has participated in such a study within the past 3 months The patient is under judicial protection, or is an adult under guardianship The patient is pregnant, parturient or breastfeeding Moribund patient Known positive serology for human immunodeficiency virus (HIV) Known positive serology for hepatitis C Known diagnosis for tuberculosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The study population<br>The study population consisted of patients admitted to the ICU for septic shock associated with secondary peritonitis and requiring antifungal therapy via echinocandins (micafungin or caspofungin). | Drug: Echinocandins<br>* The patients included in this protocol require routine treatment with caspofungin or micafungin. Though this intervention is under study, it is not modified by this protocol.<br>* Other names: caspofungin or micafungin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antifungal treatment plasmatic clearance (L/h) |  | Day 1 | 
| Antifungal treatment plasmatic clearance (L/h) |  | Days 3-5 | 
| The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration |  | Day 1 | 
| The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration |  | Days 3-5 | 
| Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration |  | Day 1 | 
| Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration |  | Days 3-5 | 
| The area under the curve for plasmatic antifungal treatment concentrations |  | Day 1 | 
| The area under the curve for plasmatic antifungal treatment concentrations |  | Days 3-5 | 
| The maximum concentration for plasmatic antifungal treatment concentrations |  | Day 1 | 
| The maximum concentration for plasmatic antifungal treatment concentrations |  | Days 3-5 | 
| The minimum concentration for plasmatic antifungal treatment concentrations |  | Day 1 | 
| The minimum concentration for plasmatic antifungal treatment concentrations |  | Days 3-5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin | corresponds to: area under the curve / minimum inhibitory concentration >865 | Day 1 | 
| The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin | corresponds to: area under the curve / minimum inhibitory concentration >865 | Days 3-5 | 
| The target Pharmacokinetic/Pharmacodynamic ratio for micafungin | corresponds to: area under the curve / minimum inhibitory concentration >285 et 3000 | Day 1 | 
| The target Pharmacokinetic/Pharmacodynamic ratio for micafungin | corresponds to: area under the curve / minimum inhibitory concentration >285 et 3000 | Days 3-5 | 
| The area under the curve for peritoneal antifungal treatment concentrations |  | Day 1 | 
| The area under the curve for peritoneal antifungal treatment concentrations |  | Days 3-5 | 
| The maximum concentration for peritoneal antifungal treatment concentrations |  | Day 1 | 
| The maximum concentration for peritoneal antifungal treatment concentrations |  | Days 3-5 | 
| The minimum concentration for peritoneal antifungal treatment concentrations |  | Day 1 | 
| The minimum concentration for peritoneal antifungal treatment concentrations |  | Days 3-5 | 
| The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio |  | Day 1 | 
| The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio |  | Days 3-5 | 
| The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio |  | Day 1 | 
| The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio |  | Days 3-5 |