Pharmacokinetics of Ciprofloxacin in Critically Ill Patients (CAPOEIRA)

• ClinicalTrials.gov Identifier: NCT03016845
• Recruitment Status: Completed
• First Posted: January 11, 2017
• Last Update Posted: October 19, 2020
• Sponsor: Radboud University
• Collaborators: Canisius-Wilhelmina Hospital; UMC Utrecht; Gelderse Vallei Hospital; Tergooi Hospital
• Information provided by (Responsible Party): Radboud University

Tracking Information

• First Submitted Date: January 9, 2017
• First Posted Date: January 11, 2017
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: January 1, 2017
• Actual Primary Completion Date: March 1, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 9, 2017)

model for estimation of renal function that most accurately predicts ciprofloxacin clearance [ Time Frame: Day 1 and day 2 ]

Full pharmacokinetic curves will be taken on Day 1 and Day 2

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

plasma samples for determination of ciprofloxacin and cystatin C Urine for measuring 24h creatinine cleaurance

• 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.
• Condition: Bacterial Infections
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Gieling EM, Wallenburg E, Frenzel T, de Lange DW, Schouten JA, Ten Oever J, Kolwijck E, Burger DM, Pickkers P, Ter Heine R, Brüggemann 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 9, 2017): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 1, 2018
• Actual Primary Completion Date: March 1, 2018 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03016845
• Other Study ID Numbers: UMCN-AFK 16.07
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Radboud University
• Study Sponsor: Radboud University

Collaborators

• Canisius-Wilhelmina Hospital
• UMC Utrecht
• Gelderse Vallei Hospital
• Tergooi Hospital

Investigators

• Principal Investigator: Roger Bruggemann; Radboud University

• PRS Account: Radboud University
• Verification Date: November 2017