Clinical trial NCT03798600: Pharmacokinetics/Pharmacodynamics (PK/PD) of Caspofungin in Intensive Care Unit (ICU) Patients. An Open Observational Study for Antifungal Treatment's Optimization
Official title: Pharmacokinetics/Pharmacodynamics (PK/PD) of Caspofungin in Intensive Care Unit (ICU) Patients. An Open Observational Study for Antifungal Treatment's Optimization
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Critical Illness
Infection
Keywords: Caspofungin
pharmacokinetic
pharmacodynamic
Lead sponsor: Careggi Hospital
Sponsor class: OTHER
First posted: 2019-01-10
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 20 patients consecutively admitted in the ICU with severe sepsis or septic shock requiring caspofungin therapy will be considered for this observational study.

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.

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)

Primary outcomes:
measure: Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: first 24 hours after loading dose
Secondary outcomes:
measure: Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
timeFrame: first 24 hours after loading dose
measure: Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
timeFrame: at day 4 after loading dose
measure: Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
timeFrame: first 24 hours after loading dose
measure: Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin
timeFrame: at day 4 after loading dose
measure: Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: first 24 hours after loading dose
measure: Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: at day 4 after loading dose
measure: Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: first 24 hours after loading dose
measure: Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: at day 4 after loading dose
measure: Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: first 24 hours after loading dose
measure: Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: at day 4 after loading dose
measure: Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: first 24 hours after loading dose
measure: Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: at day 4 after loading dose
measure: Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU).
timeFrame: at day 4 after loading dose
Other outcomes:
Locations:
Study officials:
affiliation: Azienda Careggi
name: Gianluca Villa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Adembri C, Villa G, Rosi E, Tofani L, Fallani S, De Gaudio AR, Novelli A. Caspofungin PK in critically ill patients after the first and fourth doses: suggestions for therapeutic drug monitoring? J Chemother. 2020 May;32(3):124-131. doi: 10.1080/1120009X.2020.1737783. Epub 2020 Mar 23.