Pharmacokinetics of Caspofungin (Cancidas ®) Given Intravenously as Therapy to Patients With an Invasive Fungal Infection in the Intensive Care Unit - a Search for Co-variates (CASCADE)

The pharmacokinetics of caspofungin are expected to be different in ICU patients compared to non-ICU patients. The investigators will determine caspofungin concentrations in 20 ICU patients, who will get caspofungin as standard care.

Full PK curves will be taken on day 3 and a limited PK curve on day 7, trough levels will be taken daily.

Study Overview

• Status: Completed
• Conditions: Invasive Fungal Infection
• Intervention / Treatment: Drug: caspofungin

Detailed Description

The pharmacokinetics of caspofungin are expected to be different in ICU patients compared to non-ICU patients and healthy volunteers due to underlying disease(s). Therefore, extrapolation of data from healthy volunteers and non-ICU patients is not possible.

To be able to include 20 patients within the study duration, a multi-centre approach is necessary.

Patients will receive standard care, as stated in the SPC or according to local protocols. Blood sampling for PK analysis will be retrieved through a central venous catheter. Approximately 60mL will be drawn in total for this study. Patients will be monitored daily during the treatment period for adverse events of the study drug.

Although steady state of caspofungin will be achieved after approximately 14 days of treatment, full PK curves will be taken on day 3. As probably not all patients included will be treated with caspofungin for 14 days, taking full PK curves on day 14 is considered not feasible. These two moments of PK analysis will enable the determination steady state and enable the determination of intra-individual variability.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Centre
  • Nijmegen, Netherlands
    • Canisius Wilhelmina Hospital (CWZ)
  • Utrecht, Netherlands
    • University Medical Centre Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

intensive care patients with invasive fungal infection

Description

Inclusion Criteria:

• Patient is admitted to an ICU
• Subject is at least 18 and not older than 65 years of age on the day of the first dosing
• Subject has been treated with caspofungin for a maximum of two days before enrolment in this trial
• Is managed with a central venous catheter

Exclusion Criteria:

• Is known to be hypersensitive to echinocandin antifungal agents
• Documented history of sensitivity to medicinal products or excipients similar to those found in the caspofungin preparation
• Positive HIV test or hepatitis B or C test
• History of QT time prolongation
• History of or current abuse of drugs, alcohol or solvents
• Has previously participated in this trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
caspofungin; caspofungin dosing	Drug: caspofungin; normal dosage for caspofungin, not adapted for the study; Other Names: Cancidas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve (AUC)	AUC0-tau, AUC0-inf (Time Frame: predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 20 and 24 hours post-dose on Day 3 and predose, 1, 4, 8, 12 hours + 6 days after the dose on Day 7) of caspofungin	day 3 and day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
co-variates influencing PK of caspofungin	identify co-variates of influence on the pharmacokinetics of caspofungin	day 3 and day 7
Number of Participants with Adverse Events	the adverse events will be recorded in IC patients during the study	14 days

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Roger Brüggemann, PhD, PharmD, Radboud University Medical Center

Publications and helpful links

General Publications

• Muilwijk EW, Schouten JA, van Leeuwen HJ, van Zanten AR, de Lange DW, Colbers A, Verweij PE, Burger DM, Pickkers P, Bruggemann RJ. Pharmacokinetics of caspofungin in ICU patients. J Antimicrob Chemother. 2014 Dec;69(12):3294-9. doi: 10.1093/jac/dku313. Epub 2014 Aug 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: February 10, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: candidiasis; pharmacokinetics; intensive care; aspergillosis; caspofungin; invasive fungal infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Caspofungin
• Other Study ID Numbers: AKF UMCN 11.02