Pharmacokinetics of Ciprofloxacin in Critically Ill Patients (CAPOEIRA)

Pharmacokinetics of Ciprofloxacin in Critically Ill Patients - a Screening Study to Assess the Feasibility of Renal Function Markers to Predict Ciprofloxacin Clearance (CAPOEIRA)

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.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections

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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Netherlands
  • Ede, Netherlands
    • Ziekenhuis Gelderse Vallei
  • Nijmegen, Netherlands
    • Radboudumc
  • Nijmegen, Netherlands
    • CWZ
  • Utrecht, Netherlands
    • UMC Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
model for estimation of renal function that most accurately predicts ciprofloxacin clearance	Full pharmacokinetic curves will be taken on Day 1 and Day 2	Day 1 and day 2

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: UMC Utrecht; Canisius-Wilhelmina Hospital; Gelderse Vallei Hospital; Tergooi Hospital

Publications and helpful links

General Publications

• 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.

Helpful Links

• paper

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 9, 2017
• First Posted (Estimate): January 11, 2017

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; Intensive Care Unit; renal function; Cystatin C; CKD-EPI; ciprofloxacin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: UMCN-AFK 16.07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No