Clinical trial NCT02805049: Pharmacokinetic Study on Echinocandins for Patients With Septic Shock Following Secondary Peritonitis
Official title: Pharmacokinetic Study on Echinocandins for Patients With Septic Shock Following Secondary Peritonitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Septic Shock
Peritonitis
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2016-06-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Antifungal treatment plasmatic clearance (L/h)
timeFrame: Day 1
measure: Antifungal treatment plasmatic clearance (L/h)
timeFrame: Days 3-5
measure: The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration
timeFrame: Day 1
measure: The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration
timeFrame: Days 3-5
measure: Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration
timeFrame: Day 1
measure: Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration
timeFrame: Days 3-5
measure: The area under the curve for plasmatic antifungal treatment concentrations
timeFrame: Day 1
measure: The area under the curve for plasmatic antifungal treatment concentrations
timeFrame: Days 3-5
measure: The maximum concentration for plasmatic antifungal treatment concentrations
timeFrame: Day 1
measure: The maximum concentration for plasmatic antifungal treatment concentrations
timeFrame: Days 3-5
measure: The minimum concentration for plasmatic antifungal treatment concentrations
timeFrame: Day 1
measure: The minimum concentration for plasmatic antifungal treatment concentrations
timeFrame: Days 3-5
Secondary outcomes:
measure: The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin
timeFrame: Day 1
measure: The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin
timeFrame: Days 3-5
measure: The target Pharmacokinetic/Pharmacodynamic ratio for micafungin
timeFrame: Day 1
measure: The target Pharmacokinetic/Pharmacodynamic ratio for micafungin
timeFrame: Days 3-5
measure: The area under the curve for peritoneal antifungal treatment concentrations
timeFrame: Day 1
measure: The area under the curve for peritoneal antifungal treatment concentrations
timeFrame: Days 3-5
measure: The maximum concentration for peritoneal antifungal treatment concentrations
timeFrame: Day 1
measure: The maximum concentration for peritoneal antifungal treatment concentrations
timeFrame: Days 3-5
measure: The minimum concentration for peritoneal antifungal treatment concentrations
timeFrame: Day 1
measure: The minimum concentration for peritoneal antifungal treatment concentrations
timeFrame: Days 3-5
measure: The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio
timeFrame: Day 1
measure: The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio
timeFrame: Days 3-5
measure: The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio
timeFrame: Day 1
measure: The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio
timeFrame: Days 3-5
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Royal Brisbane Women's Hospital
city: Nîmes Cedex 09
country: France
facility: CHU de Nîmes - Hôpital Universitaire Carémeau
Study officials:
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Claire Roger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.