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

• Sponsor: Centre Hospitalier Universitaire de Nīmes (Other)
• Overall Status: Completed
• CT.gov ID: NCT02805049
• Collaborator: (none)
• Enrollment: 24
• Locations: 2
• Arm: 1
• Actual Duration (Months): 16.8
• Patients Per Site: 12
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock; Peritonitis	Drug: Echinocandins	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetic Study on Echinocandins for Patients With Septic Shock Following Secondary Peritonitis
• Actual Study Start Date: Jan 28, 2017
• Actual Primary Completion Date: Jun 23, 2018
• Actual Study Completion Date: Jun 23, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Antifungal treatment plasmatic clearance (L/h) [Day 1]

2. Antifungal treatment plasmatic clearance (L/h) [Days 3-5]

3. The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration [Day 1]

4. The volume of distribution (L) corresponding to plasmatic antifungal treatment concentration [Days 3-5]

5. Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration [Day 1]

6. Intercompartmental transfer constant for a bi-compartmental model for plasmatic antifungal treatment concentration [Days 3-5]

7. The area under the curve for plasmatic antifungal treatment concentrations [Day 1]

8. The area under the curve for plasmatic antifungal treatment concentrations [Days 3-5]

9. The maximum concentration for plasmatic antifungal treatment concentrations [Day 1]

10. The maximum concentration for plasmatic antifungal treatment concentrations [Days 3-5]

11. The minimum concentration for plasmatic antifungal treatment concentrations [Day 1]

12. The minimum concentration for plasmatic antifungal treatment concentrations [Days 3-5]

Secondary Outcome Measures

1. The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin [Day 1]

   corresponds to: area under the curve / minimum inhibitory concentration >865

2. The target Pharmacokinetic/Pharmacodynamic ratio for caspofungin [Days 3-5]

   corresponds to: area under the curve / minimum inhibitory concentration >865

3. The target Pharmacokinetic/Pharmacodynamic ratio for micafungin [Day 1]

   corresponds to: area under the curve / minimum inhibitory concentration >285 et 3000

4. The target Pharmacokinetic/Pharmacodynamic ratio for micafungin [Days 3-5]

   corresponds to: area under the curve / minimum inhibitory concentration >285 et 3000

5. The area under the curve for peritoneal antifungal treatment concentrations [Day 1]

6. The area under the curve for peritoneal antifungal treatment concentrations [Days 3-5]

7. The maximum concentration for peritoneal antifungal treatment concentrations [Day 1]

8. The maximum concentration for peritoneal antifungal treatment concentrations [Days 3-5]

9. The minimum concentration for peritoneal antifungal treatment concentrations [Day 1]

10. The minimum concentration for peritoneal antifungal treatment concentrations [Days 3-5]

11. The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Day 1]

12. The probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Days 3-5]

13. The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Day 1]

14. The fraction of the probability of attaining the targeted Pharmacokinetic/Pharmacodynamic ratio [Days 3-5]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Brisbane Women's Hospital	Herston		Australia	4029
2	CHU de Nîmes - Hôpital Universitaire Carémeau	Nîmes Cedex 09		France	30029

Sponsors and Collaborators

• Centre Hospitalier Universitaire de Nīmes

Investigators

• Principal Investigator: Claire Roger, MD, Centre Hospitalier Universitaire de Nîmes

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Centre Hospitalier Universitaire de Nīmes
• ClinicalTrials.gov Identifier: NCT02805049
• Other Study ID Numbers: LOCAL/2016/CR-01
• First Posted: Jun 17, 2016
• Last Update Posted: Jan 25, 2019
• Last Verified: Jan 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Shock, Septic; Peritonitis; Shock; Caspofungin; Micafungin; Echinocandins

Study Results

No Results Posted as of Jan 25, 2019