Critical Illness, Infection
Conditions
Keywords
Caspofungin, pharmacokinetic, pharmacodynamic
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.
Interventions
DRUGCaspofungin
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.
Sponsors
Careggi Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin | first 24 hours 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 maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). | first 24 hours 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). | first 24 hours after loading dose | The caspofungin minimum serum concentrations will be described and compared with those reported in the literature for healthy volunteers. |
| Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin | first 24 hours 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 Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU). | first 24 hours after loading dose | The caspofungin elimination half life will be described and compared with those reported in the literature for healthy volunteers. |
| 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 volume distribution in septic patients admitted to the Intensive Care Unit (ICU). | first 24 hours after loading dose | The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers. |
Outcome results
None listed