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

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Peritonitis
• Intervention / Treatment: Drug: Echinocandins

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, 4029
    • Royal Brisbane Women's Hospital
• France
  • Nîmes Cedex 09, France, 30029
    • CHU de Nimes - Hopital Universitaire Caremeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The study population; 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; 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.; Other Names: caspofungin or micafungin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2017
• Primary Completion (Actual): June 23, 2018
• Study Completion (Actual): June 23, 2018

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: June 15, 2016
• First Posted (Estimate): June 17, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2019
• Last Update Submitted That Met QC Criteria: January 24, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Peritoneal Diseases; Sepsis; Intraabdominal Infections; Shock, Septic; Shock; Peritonitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Micafungin; Caspofungin; Echinocandins
• Other Study ID Numbers: LOCAL/2016/CR-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No