Clinical trial NCT03016845: Pharmacokinetics of Ciprofloxacin in Critically Ill Patients
Official title: Pharmacokinetics of Ciprofloxacin in Critically Ill Patients - a Screening Study to Assess the Feasibility of Renal Function Markers to Predict Ciprofloxacin Clearance (CAPOEIRA)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bacterial Infections
Keywords: ciprofloxacin
pharmacokinetics
Intensive Care Unit
Cystatin C
CKD-EPI
renal function
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Canisius-Wilhelmina Hospital
name: UMC Utrecht
name: Gelderse Vallei Hospital
name: Tergooi Hospital
First posted: 2017-01-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients receiving ciprofloxacin for treating a suspected or proven bacterial infection at the ICU will be included.

Brief summary: Optimal understanding of ciprofloxacin pharmacokinetics in critically ill patients is lacking resulting in large variation of achieved exposure and possible inadequate therapy. The investigators hypothesize that drug dosing based on CKD-EPIcr-cys provides a useful method to individualize and optimize therapy for ciprofloxacin and eventually improve outcome.

In a multi-centre, observational, open-label study the investigators aim to define : the model for estimation of renal function that most accurately predicts ciprofloxacin clearance in critically ill patients.

Detailed description: Correct estimation of glomerular filtration rate (GFR) is necessary in critically ill patients in order to asses renal function. GFR is subsequently used to derive and appropriate drug dosing of renally excreted drugs and warrant adequate dose adaptations.

It is known that estimation of GFR based on creatinine clearance is not precise, especially in populations with altered muscle mass or instable renal function, such as the Intensive Care Unit (ICU) population.

The use of combined filtration markers together, cystatin C and creatinine, can improve precision in estimating GFR (eGFR). Studies confirmed that eGFR based on both creatinine and cystatin C is more precise than eGFR creatinine or eGFR cystatin C. The equation based on both creatinine and cystatin C, the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C (CKD-EPIcr-cys), may therefore improve eGFR and thus drug dosing in ICU patients, a population that does not reach PK/PD targets frequently.

So far little is known about drug dosing based on CKD-EPIcr-cys. Currently optimal understanding of ciprofloxacin pharmacokinetics in critically ill patients is lacking, resulting in large variation of achieved exposure and possible inadequate therapy. The investigators hypothesize that drug dosing based on CKD-EPIcr-cys provides a useful method to individualize and optimize therapy for ciprofloxacin and eventually improve outcome.

In a multi-centre, observational, open-label study the investigators aim to define the model for estimation of renal function that most accurately predicts ciprofloxacin clearance in critically ill patients.

Eligibility criteria: Inclusion Criteria:

1. Patient is admitted to an ICU
2. Subject is at least 18 years on the day of the first dosing
3. Is managed with an arterial line or central venous catheter
4. Is managed with an urinary catheter
5. Is already treated with ciprofloxacin as part of routine clinical care

Exclusion Criteria:

1. Has previously participated in this study
2. Is on renal replacement therapy (RRT)

Primary outcomes:
measure: model for estimation of renal function that most accurately predicts ciprofloxacin clearance
timeFrame: Day 1 and day 2
Secondary outcomes:
Other outcomes:
Locations:
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Nijmegen
country: Netherlands
facility: CWZ
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: Radboud University Medical Center
name: Roger Bruggemann
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gieling EM, Wallenburg E, Frenzel T, de Lange DW, Schouten JA, Ten Oever J, Kolwijck E, Burger DM, Pickkers P, Ter Heine R, Bruggemann RJM. Higher Dosage of Ciprofloxacin Necessary in Critically Ill Patients: A New Dosing Algorithm Based on Renal Function and Pathogen Susceptibility. Clin Pharmacol Ther. 2020 Oct;108(4):770-774. doi: 10.1002/cpt.1855. Epub 2020 May 15.