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

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ClinicalTrials.gov Identifier: NCT03798600
Recruitment Status : Completed
First Posted : January 10, 2019
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
Gianluca Villa, 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.


Condition or disease Intervention/treatment
Critical Illness Infection Drug: Caspofungin

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.

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Study Type : Observational
Actual Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics/Pharmacodynamics (PK/PD) of Caspofungin in Intensive Care Unit (ICU) Patients. An Open Observational Study for Antifungal Treatment's Optimization
Actual Study Start Date : January 1, 2016
Actual Primary Completion Date : December 31, 2017
Actual Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Critically ill patients

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
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.




Primary Outcome Measures :
  1. Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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 :
  1. Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin [ Time Frame: 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.

  2. Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin [ Time Frame: 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.

  3. Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin [ Time Frame: 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.

  4. Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin [ Time Frame: 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.

  5. Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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.

  6. Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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.

  7. Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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.

  8. Alterations of Caspofungin minimum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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.

  9. Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: first 24 hours after loading dose ]
    The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.

  10. Alterations of Caspofungin volume distribution in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: at day 4 after loading dose ]
    The caspofungin volume distribution will be described and compared with those reported in the literature for healthy volunteers.

  11. Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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.

  12. Alterations of Caspofungin elimination half life in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: 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.

  13. Alterations of Caspofungin Area Under the curve (AUC) in septic patients admitted to the Intensive Care Unit (ICU). [ Time Frame: at day 4 after loading dose ]
    The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.


Biospecimen Retention:   Samples Without DNA
Serum and urine samples. To perform the PK study, blood samples (of approximately 2 ml each) will be obtained at different time points following the first administration. These samples will occur at the same time of routine blood gas analysis (hourly obtained in the ICU) and no further extra-routine blood samples will be required for this study. In particular, the blood that normally remains in the syringe of blood gas analysis, and usually thrown as waste fluid, will be saved and used for PK analysis. Thus, no increase in blood sampling from the patient will be obtained, both in terms of frequency of sampling or volume of blood.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03798600


Sponsors and Collaborators
Careggi Hospital
Investigators
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Principal Investigator: Gianluca Villa, MD Azienda Careggi
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gianluca Villa, Principal investigator, Careggi Hospital
ClinicalTrials.gov Identifier: NCT03798600    
Other Study ID Numbers: CEAVC, 32366/2015; OSS.15.114
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Gianluca Villa, Careggi Hospital:
Caspofungin
pharmacokinetic
pharmacodynamic
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes
Caspofungin
Antifungal Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action