Individualized Cefepime Dosing Study

NCT02680600 | Completed

• 1 other identifier: B126201419859
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Several population pharmacokinetic (PK) models for cefepime in critically ill patients have been described, all indicating that variability in renal clearance is the main determinant of observed variability in exposure. The main objective of this study was hence to determine which renal marker best predicts cefepime clearance.

Conditions

Antimicrobial Treatment

Outcome Measures

Primary Outcomes (2)

• Median absolute predictive error (MdAPE) of population PK model without covariates

  Evaluation during a maximum follow-up period of 5 days

• Median absolute predictive error (MdAPE) of population PK model with different renal markers incorporated

  Evaluation during a maximum follow-up period of 5 days

Secondary Outcomes (2)

• The estimated probability of target attianment (%) for the different categories of the Sanford guide

  Based on data from a maximum follow-up period of 5 days

• The estimated probability of toxic levels (%) for the different categories of the Sanford guide

  Based on data from a maximum follow-up period of 5 days

Study Arms (1)

Study arm

EXPERIMENTAL

* Cefepime dosing * Blood sampling * Urine sampling * Determination of renal markers * Population pharmacokinetic modeling * Covariate screening * Monte Carlo simulations

Drug: Cefepime dosing; Other: Blood sampling; Other: Urine sampling; Other: Determination of renal markers; Other: Population pharmacokinetic modeling; Other: Covariate screening; Other: Monte Carlo simulations

Interventions

Cefepime dosing DRUG

Patients will received cefepime administered per standard-of-care as a 30 min intravenous infusion. Dosing will be based on local guidelines (the Sanford guide to antimicrobial therapy 2012-2013) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine formula to estimate glomerular filtration rate (GFR).

Also known as: Cefepime administration

Study arm

Blood sampling OTHER

Blood will be sampled immediately prior to dose administration (time = 0 at the start of the 30 min infusion), at 0.5, 1, 3, 5 hours post-start of infusion and just before the subsequent dose. From day two onwards, samples will be taken at the end of the infusion and just before the next dose. For the quantification of cefepime, a validated solid phase extraction-liquid chromatography electrospray-tandem mass spectrometry method will be used.

Study arm

Urine sampling OTHER

Timed urine collections were taken during one dosing interval (8 hours in a three times daily regimen) every day.

Study arm

Determination of renal markers OTHER

Creatinine (modified Jaffe method) and urea in serum will be determined using an Architect c16000 analyzer (Abbott, Chicago, IL, USA). Cystatin C will be determined using a particle-enhanced immunonephelometric assay (N Latex Cystatin C, Siemens Healthcare Diagnostics, Marburg, Germany) by use of a BN II nephelometer (Siemens Healthcare Diagnostics). This assay has a calibration traceable to the first certified reference material for cystatin C in human serum (ERM-DA471/IFCC). Kidney injury molecule-1 (KIM-1) in urine and uromodulin in serum will be determined using commercially available ELISA assays: Quantikine ELISA Human TIM-1/KIM-1/HAVCR (R\&D Systems, Minneapolis, MN, USA) and Uromodulin ELISA (Euroimmun, Luebeck, Germany), respectively.

Study arm

Population pharmacokinetic modeling OTHER

The cefepime concentration versus time data will be fitted using the FOCE-I estimation algorithm in NONMEM® (Version 7.3; GloboMax LLC, Hanover, MD, USA). R® (R foundation for statistical computing, Vienna, Austria) will be used to graphically assess the model's goodness-of-fit and to evaluate the model's predictive capabilities. As a measure of prediction error, the absolute prediction error (APE) will be used. In short, the measured cefepime concentrations for each individual i at time point j were compared against the population predicted cefepime concentrations, i.e. the predictions for each individual without taking into account the between-subject variability (PRED in NONMEM). The distribution of APEs will be summarized by the median and 90% percentile.

Study arm

Covariate screening OTHER

Renal function will be assessed by four serum based kidney markers (serum creatinine, cystatin C, urea and uromodulin) and two urinary markers (measured creatinine clearance (CrCl) and KIM-1, both on timed urine collections). Serum creatinine and cystatin C will also be used to calculate the eGFR based on CKD-EPI formulas.

Study arm

Monte Carlo simulations OTHER

Based on the final covariate model, a Monte Carlo-based simulation study will be performed to evaluate the Sanford dose recommendations for ICU patients.

Study arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age 18 years or more
• Hospitalized in the ICU of OLV hospital Aalst
• Elected by the treating physician to receive cefepime,irrespectively of the study
• Presence of arterial or central line for blood sampling

You may not qualify if:

• Exact time of cefepime administration or blood sampling unknown
• No written informed consent by the patient or his/her (legal) representative

Sponsors & Collaborators

• Onze Lieve Vrouw Hospital: lead
• University Ghent: collaborator

Related Publications (24)

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  PMID: 18313273 BACKGROUND

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  PMID: 25052578 BACKGROUND

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MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Stijn Jonckheere

  Onze Lieve Vrouw Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2016
• First Posted: February 11, 2016
• Study Start: March 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: January 1, 2016
• Last Updated: February 12, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share