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

NCT03798600 | Completed FDA Drug

• 1 other identifier: CEAVC, 32366/2015; OSS.15.114
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Critical Illness; Infection

Keywords

Caspofungin; pharmacokinetic; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin

  first 24 hours after loading dose

• Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin

  at day 4 after loading dose

• Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin

  first 24 hours after loading dose

• Alterations of AUC/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin

  at day 4 after loading dose

• Alterations of Caspofungin maximum serum concentrations in septic patients admitted to the Intensive Care Unit (ICU).

  first 24 hours after loading dose

Study Arms (1)

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

Interventions

Caspofungin DRUG

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.

Critically ill patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Careggi Hospital: lead

Related Publications (1)

• 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.

  PMID: 32202224 DERIVED

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.

MeSH Terms

Conditions

Critical Illness; Infections

Interventions

Caspofungin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Echinocandins; Peptides, Cyclic

Study Officials

• Gianluca Villa, MD

  Azienda Careggi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 10, 2019
• Study Start: January 1, 2016
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2018
• Last Updated: January 17, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share