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

Study Overview
=================
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.

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

Conditions
-----------------
Critical Illness, Infection

Intervention / Treatment
-----------------
* Drug: Caspofungin


Participation Criteria
=================
Eligibility Criteria
-----------------
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)
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Critically ill patients<br>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) | Drug: Caspofungin<br>* In accordance with routine clinical practice, Caspofungin will be given at the loading dose of 70 mg followed by 50 mg daily (for people < 80 kg body weight). No dose reduction will be performed in Child-Pugh score A or B. Duration of therapy will be performed in accordance with ESCMID guidelines and clinical conditions.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin | The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication. | first 24 hours after loading dose | 
| Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin | The Cmax/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication. | at day 4 after loading dose | 
| Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin | The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication. | first 24 hours after loading dose | 
| Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin | The AUC/MIC ratio, will be calculated and compared with that reported in the literature to obtain the infection eradication. | at day 4 after loading dose | 
| Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers. | first 24 hours after loading dose | 
| Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin maximum serum concentrations will be described and compared with those reported in the literature for healthy volunteers. | at day 4 after loading dose | 
| Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers. | first 24 hours after loading dose | 
| Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers. | at day 4 after loading dose | 
| Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers. | first 24 hours after loading dose | 
| Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers. | at day 4 after loading dose | 
| Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers. | first 24 hours after loading dose | 
| Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers. | at day 4 after loading dose | 
| Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU). | The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers. | at day 4 after loading dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Caspofungin, pharmacokinetic, pharmacodynamic