Antibiotic Dosing in Patients on Intermittent Hemodialysis

Hemodialysis Clinical Trial

Official title:

Antibiotic Dosing in Patients on Intermittent Hemodialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03909698
• Other study ID #: UGent_ABdosing
• Status: Completed
• Start date: September 15, 2016
• Est. completion date: March 31, 2022

Study information

• Verified date: August 2021
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The adequacy of the currently used dosing regimen of glycopeptides (vancomycin and teicoplanin) and beta-lactam antibiotics (amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidim) in patients with end-stage kidney disease receiving intermittent hemodialysis is studied by evaluating pharmacokinetics-pharmacodynamics (PK-PD) target attainment. A population pharmacokinetic study is performed to assist the selection of the optimal individualized dose for patients undergoing intermittent dialysis, taking into consideration as many relevant variables as possible.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with end-stage kidney disease, requiring intermittent hemodialysis

• patient receiving antibiotic treatment for documented or presumed infection (vancomycin, teicoplanin, amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidim)

Exclusion Criteria:

• pregnant woman

• absence of written informed consent from the patient

• known hypersensitivity or contra-indication to glycopeptides or beta-lactam antibiotics

Related Conditions & MeSH terms

• Antibiotics
• Hemodialysis
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Other:
• Blood and urine sampling
During a period of maximum 6 days blood is sampled at different time points and urine is collected during documented time intervals.

Locations

Country	Name	City	State
Belgium	Ghent University Hospital	Gent

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Ghent	University Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood concentrations with maximal antimicrobial activity versus current dosing regimens for vancomycin	Measured free and total concentration of the glycopeptide vancomycin is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: Area Under the Curve (AUC) from 0-24h in steady-state divided by the Minimum Inhibitory Concentration (MIC) of the suspected pathogen should be >=400 for vancomycin.	9/2016 - 12/2021
Primary	Blood concentrations with maximal antimicrobial activity versus current dosing regimens for teicoplanin	Measured free and total concentration of the glycopeptide teicoplanin is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: Area Under the Curve (AUC) from 0-24h in steady-state divided by the Minimum Inhibitory Concentration (MIC) of the suspected pathogen should be >=750 for teicoplanin.	9/2016 - 12/2021
Primary	Blood concentrations with maximal antimicrobial activity versus current dosing regimens for amoxicillin-clavulanic acid	Measured concentration of the beta-lactam amoxicillin-clavulanic acid is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%.	9/2016 - 12/2021
Primary	Blood concentrations with maximal antimicrobial activity versus current dosing regimens for piperacillin-tazobactam	Measured concentration of the beta-lactam piperacillin-tazobactam is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%.	9/2016 - 12/2021
Primary	Blood concentrations with maximal antimicrobial activity versus current dosing regimens for ceftazidim	Measured concentration of the beta-lactam ceftazidim is compared to predefined pharmacokinetic/pharmacodynamic (PK-PD) targets: minimum percentage of time during which the free drug concentration remains above the Minimum Inhibitory Concentration (MIC) of the micro-organism should be 50%.	9/2016 - 12/2021
Primary	Pharmacokinetics of vancomycin in patients undergoing intermittent hemodialysis	Population pharmacokinetic modeling is performed based on the measured vancomycin concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured vancomycin concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.	9/2016 - 12/2021
Primary	Pharmacokinetics of teicoplanin in patients undergoing intermittent hemodialysis	Population pharmacokinetic modeling is performed based on the measured teicoplanin concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured teicoplanin concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.	9/2016 - 12/2021
Primary	Pharmacokinetics of amoxicillin-clavulanic acid in patients undergoing intermittent hemodialysis	Population pharmacokinetic modeling is performed based on the measured amoxicillin-clavulanic acid concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured amoxicillin-clavulanic acid concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.	9/2016 - 12/2021
Primary	Pharmacokinetics of piperacillin-tazobactam in patients undergoing intermittent hemodialysis	Population pharmacokinetic modeling is performed based on the measured piperacillin-tazobactam concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured piperacillin-tazobactam concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.	9/2016 - 12/2021
Primary	Pharmacokinetics of ceftazidim in patients undergoing intermittent hemodialysis	Population pharmacokinetic modeling is performed based on the measured ceftazidim concentrations, to end up with a calibrated kinetic model. The model is fitted on the measured ceftazidim concentrations in order to determine the model parameters: distribution volume and (inter)dialytic elimination rate constant and clearance.	9/2016 - 12/2021
Secondary	Dialyser extraction rate of vancomycin	From dialyser inlet and outlet samples, the extraction ratio is calculated for vancomycin and entered in the kinetic analysis	9/2016 - 12/2021
Secondary	Dialyser extraction rate of teicoplanin	From dialyser inlet and outlet samples, the extraction ratio is calculated for teicoplanin and entered in the kinetic analysis	9/2016 - 12/2021
Secondary	Dialyser extraction rate of amoxicillin-clavulanic acid	From dialyser inlet and outlet samples, the extraction ratio is calculated for amoxicillin-clavulanic acid and entered in the kinetic analysis	9/2016 - 12/2021
Secondary	Dialyser extraction rate of piperacillin-tazobactam	From dialyser inlet and outlet samples, the extraction ratio is calculated for piperacillin-tazobactam and entered in the kinetic analysis	9/2016 - 12/2021
Secondary	Dialyser extraction rate of ceftazidim	From dialyser inlet and outlet samples, the extraction ratio is calculated for ceftazidim and entered in the kinetic analysis	9/2016 - 12/2021