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

• Sponsor: Careggi Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03798600
• Collaborator: (none)
• Enrollment: 20
• Actual Duration (Months): 36

Study Details

Study Description

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	Phase
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.

Study Design

• 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: Jan 1, 2016
• Actual Primary Completion Date: Dec 31, 2017
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm

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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Alterations of Cmax/MIC target - which guarantees the maximal exposure of Candida spp to caspofungin [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 [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 [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). [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). [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). [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). [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). [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). [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). [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). [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). [at day 4 after loading dose]

    The caspofungin AUC will be described and compared with that reported in the literature for healthy volunteers.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Careggi Hospital

Investigators

• Principal Investigator: Gianluca Villa, MD, Azienda Careggi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gianluca Villa, Principal investigator, Careggi Hospital
• ClinicalTrials.gov Identifier: NCT03798600
• Other Study ID Numbers: CEAVC, 32366/2015; OSS.15.114
• First Posted: Jan 10, 2019
• Last Update Posted: Jan 17, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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, Principal investigator, Careggi Hospital: Caspofungin; pharmacokinetic; pharmacodynamic
• Additional relevant MeSH terms: Critical Illness; Caspofungin

Study Results

No Results Posted as of Jan 17, 2019