Pharmacokinetics/Pharmacodynamics (PK/PD) of Caspofungin in Intensive Care Unit (ICU) Patients. An Open Observational Study for Antifungal Treatment's Optimization

Completed

• Conditions: Critical Illness; Infection
• Interventions: Drug: Caspofungin

• Registration Number: NCT03798600
• Lead Sponsor: Careggi Hospital

Brief Summary

PK of Caspofungin in ICU septic patients might be changed as compared to healthy volunteers due to sepsis-related pathophysiology.

Sub-optimal plasma and tissue concentrations might be achieved in these patients when drugs are administered at the same dosage/regimen suggested for healthy volunteers.

Detailed Description

Open non randomized, non controlled single center study on the pharmacokinetics of caspofungin in 20 consecutive ICU patients with severe sepsis or septic shock, requiring caspofungin therapy and PK-PD evaluation for the optimization of caspofungin therapy. The aim of this study is to describe the Caspofungin PK-PD alterations in a cohort of critically ill septic patients.

Study Timeline

• Study Start: 2016-01-01
• Primary Completion: 2017-12-31
• Study Completion: 2018-12-31
• Status Verified: 2019-01
• Study First Submitted: 2019-01-04
• Study First Submitted QC: 2019-01-07
• Study First Posted: 2019-01-10
• Last Update Submitted: 2019-01-15
• Last Update Posted: 2019-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Adult ICU patients (>18 yrs)
• Severe sepsis or septic shock
• Caspofungin therapy based on clinical judgement (empiric therapy) or microbiological result (targeted therapy).

Exclusion Criteria

• Concomitant ciclosporin or rifampicin therapy.
• Pregnancy
• Continuous renal replacement therapy
• Severe Liver failure (Child Pugh score > 6)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Critically ill patients	Caspofungin	20 patients consecutively admitted in the ICU with severe sepsis or septic shock requiring caspofungin therapy will be considered for this observational study. Inclusion Criteria: Adult ICU patients (\>18 yrs) with severe sepsis or septic shock undergoing caspofungin therapy based on clinical judgement (empiric therapy) or microbiological result (targeted therapy). Exclusion criteria: Concomitant ciclosporin or rifampicin therapy. Pregnancy Continuous renal replacement therapy Severe Liver failure (Child Pugh score \> 6)

Primary Outcome Measures

Name	Time	Method
Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).	first 24 hours after loading dose	The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.

Secondary Outcome Measures

Name	Time	Method
Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin	at day 4 after loading dose	The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.
Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin	at day 4 after loading dose	The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication.
Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).	at day 4 after loading dose	The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.
Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).	at day 4 after loading dose	The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.
Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).	at day 4 after loading dose	The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers.
Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).	at day 4 after loading dose	The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.
Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).	at day 4 after loading dose	The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers.